Valsartan and hydrochlorothiazide (HCTZ) are used together in a once daily oral preparation to manage hypertension. Hydrochlorothiazide is a thiazide diuretic which enhances sodium and chloride excretion. Valsartan is a specific angiotensin II antagonist which selectively and competitively blocks the AT1 receptor, which mediates the vasopressor and aldosterone effects of angiotensin II. Compared to losartan, valsartan has a similar efficacy and safety profile, but does not have an active metabolite or possess uricosuric effects. Because valsartan does not inhibit angiotensin converting enzyme (ACE), it does not result in bradykinin accumulation which is theorized to cause the cough and angioedema associated with ACE inhibitors. However, angioedema has been rarely associated with valsartan or other angiotensin II antagonists. Because AT1 receptors are nearly saturated at the starting dose for most angiotensin II antagonists, the antihypertensive dose-response curve of these drugs are nonlinear, with proportionally small decreases in blood pressure attained with increased dosage. Greater antihypertensive efficacy is achieved by adding a small dose of a diuretic to the angiotensin II antagonist. Valsartan tends to reverse the potassium loss, but not the rise in serum uric acid levels associated with hydrochlorothiazide. Diovan HCT was approved for US marketing by the FDA on March 10, 1998.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May administer valsartan; hydrochlorothiazide without regard to meals.
Valsartan; hydrochlorothiazide is generally well-tolerated; adverse events are generally mild and transient. The overall incidence of adverse reactions in treatment groups was comparable to placebo in clinical trials. Valsartan; hydrochlorothiazide has been evaluated for safety in over 5700 patients. The incidence of discontinuation of valsartan; hydrochlorothiazide due to drug-related adverse effects was higher in placebo than in valsartan; hydrochlorothiazide-treated patients (3.1% vs. 2.3%, respectively).
In July 2010, the FDA released a Medwatch alert announcing the possibility of an increased risk of malignancy in patients taking angiotensin receptor blockers (ARBs), such as valsartan, for the treatment of hypertension.This announcement was based on results of a meta-analysis including data from over 1000 patients in several long-term, randomized, controlled clinical trials evaluating ARBs. The frequency of new cancer occurrence was 7.2% for patients receiving ARBs compared to 6% for those not receiving ARBs (RR = 1.08, 95% CI, 1.01 to 1.15). In June 2011, the FDA announced that the use of ARBs for hypertension does not increase the risk for cancer. The FDA analyzed data from 31 randomized controlled trials (including 155,000 patients) comparing ARBs to other treatments. Based on these data, the FDA concluded that there is no evidence of an increased risk of new cancer, cancer-related death, breast cancer, lung cancer, or prostate cancer in patients receiving ARBs.
In a clinical study in patients with severe hypertension, hypotension was observed in 1% of those patients receiving valsartan; hydrochlorothiazide and 0% of patients receiving valsartan. Excessive hypotension was rarely seen (0.7%) in patients with uncomplicated hypertension treated with valsartan; hydrochlorothiazide in controlled trials. Symptomatic hypotension is more likely to occur in patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics. This condition should be corrected prior to administration of valsartan; hydrochlorothiazide, or the treatment should start under close medical supervision. If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
The incidence of cough is lower with valsartan than with an angiotensin converting enzyme inhibitor (ACEI). Valsartan does not inhibit angiotensin converting enzyme (kinase II). Inhibition of kinase II decreases bradykinin breakdown and is thought to be the primary mechanism for ACEI-induced cough. In comparative studies, the incidence of dry cough was 7.9% in ACEI-treated patients compared with 2.6% in valsartan-treated patients and 1.5% in placebo-treated patients. Dyspnea, cough, nasal congestion or sinus congestion, and pharyngolaryngeal pain were also reported in more than 0.2% of valsartan; hydrochlorothiazide-treated patients in controlled clinical trials reported by the manufacturer. Epistaxis and bronchospasm were reported less frequently.
The most common reasons for discontinuation of valsartan; hydrochlorothiazide in clinical trials were headache and dizziness; however, the exact incidence was not reported. Dizziness was dose-related in individual trials (more than 0.2% to 6%). In a clinical study in patients with severe hypertension, dizziness was observed in 6% of patients who were force-titrated to valsartan; hydrochlorothiazide 320/25 mg/day compared to 2% of patients force-titrated to valsartan 320 mg/day. Adverse experiences (without regard to causality) in clinical trials that occurred in more than 0.2% of patients receiving valsartan; hydrochlorothiazide included: fatigue, diarrhea, impotence (erectile dysfunction) and postural dizziness. The orthostatic effects of valsartan; hydrochlorothiazide are dose-related, occurring in less than 1% of patients. The incidence of orthostatic hypotension and syncope may be reduced by proper titration of valsartan; hydrochlorothiazide. Syncope was reported infrequently in clinical trials but has also been reported during postmarketing experience. Although infrequent with low doses of thiazide diuretics, complications of diuretic therapy may include intravascular volume depletion (hypovolemia).
Clinically significant laboratory abnormalities are rarely reported with valsartan; hydrochlorothiazide. In controlled trials of various doses of valsartan; hydrochlorothiazide, hypokalemia (serum potassium less than 3.5 mEq/L) occurred in 3% patients; whereas hyperkalemia (serum potassium more than 5.7 mEq/L) occurred in 0.4%. Increases in serum potassium have been reported with valsartan in patients with heart failure and are more likely to occur if there is pre-existing renal impairment. Although these effects are usually minor and transient, dosage adjustment or discontinuation of therapy may be required. Monitoring of serum electrolytes is recommended. According to the manufacturer, if hypokalemia is accompanied by clinical signs (e.g., muscular weakness, paresis, or ECG alterations), valsartan; hydrochlorothiazide should be discontinued. Occasionally, elevated hepatic enzymes have been reported in patients receiving valsartan; hydrochlorothiazide (incidence unknown). Rare cases of hepatitis have been reported during postmarketing experience with valsartan; hydrochlorothiazide. Thiazide diuretics have been associated with intrahepatic cholestatic jaundice and hyperbilirubinemia.
Thiazide diuretics such as hydrochlorothiazide have been associated with hyperglycemia, especially at higher doses, and glycosuria; similar effects may occur with valsartan; hydrochlorothiazide.
Adverse dermatologic reactions to hydrochlorothiazide are uncommon but may occur. These reactions include purpura, photosensitivity, urticaria, erythema multiforme, Stevens-Johnson syndrome, and exfoliative dermatitis including toxic epidermal necrolysis (TEN). Hyperhidrosis and rash have been reported in more than 0.2% of valsartan; hydrochlorothiazide-treated patients in controlled clinical trials; pruritus, flushing, and sunburn were reported less frequently. Alopecia and bullous rash have been reported in valsartan or valsartan; hydrochlorothiazide postmarketing experience.
Thiazide diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Thiazides may also decrease urinary calcium excretion and may cause intermittent and slight elevations of serum calcium in the absence of known disorders of calcium metabolism. The development of marked hypercalcemia may be evidence of hidden hyperparathyroidism. If hypercalcemia occurs, valsartan; hydrochlorothiazide should be discontinued before carrying out tests for parathyroid function.
Angiotensin receptor antagonists have been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure (unspecified) and/or death in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure). Thiazides may also precipitate azotemia in patients with renal disease. In clinical trials, minor elevations in serum creatinine and BUN occurred in 2% and 15% of patients, respectively. Pollakiuria (increased urinary frequency) has been reported in more than 0.2% of valsartan; hydrochlorothiazide-treated patients in controlled clinical trials. Dysuria and gout were reported less frequently. Renal failure, renal dysfunction, and interstitial nephritis have been reported during hydrochlorothiazide monotherapy. Impaired renal function was also reported with valsartan monotherapy. Hyperuricemia may occur in patients receiving thiazide diuretics. In predisposed individuals, frank gout or nephrolithiasis may be precipitated. Diuretic-induced acute gouty arthritis and nephrolithiasis are extremely rare in patients with no prior history of gout. If some manifestation of gout occurs in a patient who requires diuretic therapy for effective treatment of hypertension, allopurinol or a uricosuric agent can be given to prevent recurrent gouty attacks without diminishing the antihypertensive effect of valsartan; hydrochlorothiazide.
Although hypercholesterolemia and/or hypertriglyceridemia have been associated with thiazide diuretic therapy, data from long-term studies suggest that diuretic-induced lipid abnormalities are not clinically significant. After approximately one year of treatment, total serum cholesterol concentrations will subside to baseline or lower, suggesting that diuretic therapy does not increase coronary heart disease risk. Nevertheless, it would be prudent to monitor serum cholesterol and triglyceride concentrations periodically in hypertensive patients receiving valsartan; hydrochlorothiazide.
Arthralgia, asthenia, back pain, muscle cramps, myalgia, and pain in extremity have been reported in more than 0.2% of valsartan; hydrochlorothiazide-treated patients in controlled clinical trials. Myasthenia was reported less frequently. Weakness and muscle spasm have been reported with hydrochlorothiazide, without regard to causality.
Rhabdomyolysis is possible during valsartan; hydrochlorothiazide therapy. Rare cases of rhabdomyolysis have been reported during postmarketing experience with angiotensin II receptor antagonists like valsartan.
Pancreatitis has been reported rarely in patients receiving thiazide diuretics. Pancreatitis can occur within 2 weeks of initiation of therapy or after several months of therapy. If signs and/or symptoms suggestive of pancreatitis develop in a patient receiving valsartan; hydrochlorothiazide, drug therapy should be discontinued.
Drugs that affect the renin-angiotensin system have been associated with fetal and neonatal abnormalities when administered to women during the second or third trimesters of pregnancy. Adverse fetal and neonatal effects have included hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, oligohydramnios, and death. Oligohydramnios has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Due to the potential for teratogenesis, valsartan; hydrochlorothiazide should not be used during pregnancy.
Valsartan; hydrochlorothiazide may result in ophthalmic adverse reactions. Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. Discontinue hydrochlorothiazide as rapidly as possible and consider prompt medical or surgical treatment if the ocular hypertension remains uncontrolled. Abnormal vision was reported infrequently during clinical trials of valsartan; hydrochlorothiazide. Transient blurred vision and xanthopsia have also been reported during hydrochlorothiazide monotherapy.
Naso-pharyngitis was the only adverse reaction that occurred in controlled clinical trials in at least 2% of patients treated with valsartan; hydrochlorothiazide and at a higher incidence than placebo (2.4% vs. 1.9%, respectively). Other infectious adverse reactions reported in more than 0.2% of valsartan; hydrochlorothiazide treated patients in controlled clinical trials include: fever, bronchitis, bronchitis acute, influenza, gastroenteritis, sinusitis, upper respiratory tract infection, and urinary tract infection. Pharyngitis and viral infection were among the less frequently reported adverse reactions.
Various hypersensitivity reactions may occur with valsartan; hydrochlorothiazide. Anaphylactic reactions (anaphylactoid reactions) and angioedema have been reported rarely during valsartan postmarketing experience. Theoretically, angiotensin II receptor antagonists (ARBs) should be less likely than angiotensin converting enzyme inhibitors (ACEIs) to precipitate angioedema because ARBs do not cause accumulation of kinins. However, angioedema (swelling of lips and eyelids, facial rash) has been reported in patients receiving ARBs, including in patients with a prior history of angioedema during ACE inhibitor therapy. Thus, clinicians should be aware of the possibility of angioedema in patients receiving valsartan; hydrochlorothiazide. Other types of hypersensitivity reactions that have been reported with valsartan; hydrochlorothiazide use include purpura, photosensitivity, urticaria, necrotizing angitis (vasculitis and cutaneous vasculitis), fever, pneumonitis, and pulmonary edema.
Palpitations, sinus tachycardia, chest pain (unspecified), and peripheral edema have been reported in more than 0.2% of valsartan; hydrochlorothiazide treated patients in controlled clinical trials.
Drowsiness, insomnia, anxiety, paresthesias, tinnitus, and vertigo have been reported in more than 0.2% of valsartan; hydrochlorothiazide treated patients in controlled clinical trials. Depression and libido decrease were reported less frequently. Restlessness has been reported during hydrochlorothiazide monotherapy.
Dyspepsia, diarrhea, flatulence, xerostomia, nausea, abdominal pain, abdominal pain upper, and vomiting have been reported in more than 0.2% of valsartan; hydrochlorothiazide treated patients in controlled clinical trials. Constipation, dehydration, and appetite stimulation were reported less frequently. Anorexia has been reported infrequently with valsartan monotherapy (incidence unknown). Sialadenitis, cramping, and gastric irritation have been reported with hydrochlorothiazide, without regard to causality.
Patients receiving valsartan; hydrochlorothiazide should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia. Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Significant decreases (more than 20%) in hemoglobin and hematocrit occurred in less than 0.1% of patients who received valsartan; hydrochlorothiazide in clinical trials, although the reported incidence was higher than in placebo-treated patients (0%). Neutropenia was observed in 0.1% of patients treated with valsartan; hydrochlorothiazide. While serious hematological reactions are rare with valsartan; hydrochlorothiazide therapy, aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, and thrombocytopenia have been reported with hydrochlorothiazide without regard to causality.
Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer. An FDA Sentinel Initiative study found that increased risk was mostly for squamous cell carcinoma and in White patients taking large cumulative doses. The increased risk for the overall population was approximately 1 additional case per 16,000 patients per year. For White patients taking a cumulative dose more than 50,000 mg, the risk increased to approximately 1 additional case per 6,700 patients per year.
Thiazide diuretics such as hydrochlorothiazide have been associated with a slight increase in serum cholesterol and triglyceride concentrations. Data from long-term studies, however, suggest diuretic-induced cholesterol changes are not clinically significant and do not contribute to coronary heart disease risk.
Thiazide diuretics are contraindicated in patients with known thiazide diuretic hypersensitivity. According to the manufacturer, hydrochlorothiazide is specifically contraindicated in patients with sulfonamide hypersensitivity. Hypersensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma; however, reactions are more likely to occur in patients with such history. Although thiazide diuretics are sulfonamide derivatives, sulfonamide cross-sensitivity has been rarely documented. Until further data are available, thiazide diuretics should be used with caution in patients with sulfonamide hypersensitivity. Thiazide diuretics do not contain the N4-aromatic amine or the N1-substituent which are present in sulfonamide antibiotics. Non-arylamine sulfonamide derivatives, such as thiazide diuretics, have been proposed to have a lower risk of allergic reactions in patients with sulfonamide allergy, presumably due to lack of an arylamine group at the N4 position (a proposed structural site of action for sulfonamide allergy). One large retrospective cohort study has reported that in patients with the presence of an allergic reaction after exposure to a sulfonamide antibiotic, 9.9% had an allergic reaction after receiving a non-antibiotic sulfonamide derivative, while in patients who lacked an allergic reaction after sulfonamide antibiotic exposure, 1.6% had an allergic reaction after administration of a non-antibiotic sulfonamide derivative (adjusted odds ratio 2.8; 95% CI, 2.1 to 3.7). A causal relationship between sulfonamide hypersensitivity and allergic reactions with non-arylamine sulfonamide derivatives has not been definitively established and remains controversial. In general, patients with a documented sulfonamide allergy are considered to be predisposed for development of allergic drug reactions. Also, patients with a history of sulfonamide hypersensitivity or penicillin hypersensitivity who receive hydrochlorothiazide may also be at increased risk for the development of an idiosyncratic reaction resulting in transient myopia and acute angle-closure glaucoma. Discontinue hydrochlorothiazide promptly if this reaction occurs.
Valsartan; hydrochlorothiazide is contraindicated in patients with anuria since thiazide diuretics are considered ineffective when the creatinine clearance is less than 30 ml/minute. Hydrochlorothiazide should be used cautiously in patients with renal disease resulting in severe renal impairment or renal failure because the drug decreases the glomerular filtration rate and may precipitate azotemia in these patients. Valsartan should be used with caution in patients whose renal function is critically dependent on the activity of the renin-angiotensin-aldosterone system (RAS) (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion). These patients may be at particular risk for developing acute renal failure during valsartan; hydrochlorothiazide therapy. Increases in serum potassium have been reported with valsartan therapy in patients with heart failure and are more likely to occur if there is pre-existing renal impairment. Although these effects are usually minor and transient, dosage reduction or discontinuation of therapy may be required. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor antagonists affect the RAS system and have caused increases in serum creatinine in susceptible individuals. Although serum creatinine returns to baseline or stabilizes in most patients with continued use, oliguria, progressive azotemia, and rarely, acute renal failure have occurred. Renal function should be monitored in patients receiving valsartan; hydrochlorothiazide. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function.
Valsartan; hydrochlorothiazide should be used with caution in patients with severe hepatic disease. Patients with mild to moderate hepatic impairment, including those with biliary obstruction, have significantly increased plasma valsartan concentrations (two-fold increase in AUC) compared to patients with normal hepatic function. Although no specific initial dosage adjustment is recommended; care should be exercised when dosing valsartan; hydrochlorothiazide in these patients. Dosage increases should be made cautiously. Hydrochlorothiazide should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Valsartan; hydrochlorothiazide should be used with caution in patients who have hypovolemia. Intravascular volume depletion increases the risk of acute renal failure and symptomatic hypotension during therapy. Volume depletion should be corrected prior to the administration of valsartan; hydrochlorothiazide. When initiating therapy in these patients, lower doses are recommended. Valsartan; hydrochlorothiazide should be used with great care in patients who exhibit signs of hypotension. Orthostatic hypotension may occur during treatment with thiazide diuretics. Orthostatic hypotension can be exacerbated by concurrent use of alcohol, narcotics, or antihypertensive drugs. Excessive hypotension during thiazide diuretic therapy can result in syncope. An increased risk of falls has been reported for elderly patients receiving thiazide diuretics. In addition, the antihypertensive effects of thiazides may be enhanced in other patients predisposed for orthostatic hypotension, including the post-sympathectomy patient.
Anaphylactic reactions (anaphylactoid reactions) and angioedema have been reported with angiotensin II receptor antagonists like valsartan. Theoretically, angiotensin II receptor antagonists should be less likely than angiotensin converting enzyme inhibitors (ACEIs) to precipitate angioedema because angiotensin II receptor antagonists do not cause accumulation of kinins. However, angioedema (swelling of lips and eyelids, facial rash) has been rarely reported in patients receiving angiotensin II receptor antagonists, including in patients with a prior history of ACE-inhibitor induced angioedema. While angiotensin II receptor antagonists have been suggested as potential alternatives to ACE inhibitors for patients who experience angioedema due to a lower frequency of associated angioedema , the safety of angiotensin II receptor antagonists in patients with a prior history of ACE-inhibitor induced angioedema. It is prudent to use substantial caution when prescribing angiotensin II receptor antagonists in patients with a history of ACE-inhibitor induced angioedema. Some authors have recommended that angiotensin II receptor antagonists should be avoided in patients with a history of angioedema, especially those with ACE-inhibitor induced angioedema.
In patients undergoing major surgery or during anesthesia with agents that lower blood pressure, valsartan may enhance hypotensive effects via angiotensin II blockade. Therefore, valsartan; hydrochlorothiazide should be used with caution prior to surgery. If hypotension occurs during surgery and/or anesthesia and is considered to be due to blockade of angiotensin II formation, it can be corrected by volume expansion.
Patients with pre-existing significant hyponatremia, hyperkalemia, hypokalemia, hypomagnesemia, or hypercalcemia should have their electrolyte imbalances corrected before valsartan; hydrochlorothiazide is initiated. Thiazide diuretics such as hydrochlorothiazide have been shown to increase the urinary excretion of magnesium and decrease urinary calcium excretion. Thiazides may worsen dilutional hyponatremia, especially in elderly individuals. Greater sensitivity to the usual dosage of valsartan and/or hydrochlorothiazide may also occur in elderly patients. Dosage should be adjusted based on clinical response. Valsartan; hydrochlorothiazide may reduce, elevate or leave potassium levels unchanged in individual patients. Increases in serum potassium have been reported with valsartan therapy in patients with heart failure and are more likely to occur if there is pre-existing renal impairment. Although these effects are usually minor and transient, dosage reduction or discontinuation of therapy may be required. All patients should be monitored closely for clinical signs of fluid or electrolyte imbalance.
When pregnancy is detected, discontinue valsartan; hydrochlorothiazide therapy as soon as possible. Women of child-bearing age should be made aware of the potential risk of fetal harm when valsartan; hydrochlorothiazide is taken during pregnancy. When used during the second and third trimesters of pregnancy, medications that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce renal function and increase fetal and neonatal morbidity and death. Use of drugs that affect the renin-angiotensin system during pregnancy can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, reversible or irreversible renal failure and death. Anhydramnios and oligohydramnios have also been reported. Development of oligohydramnios may be associated with decreased fetal renal function leading to anuria and renal failure and results in fetal limb contractures, craniofacial deformation, hypotension, hypoplastic lung development, and death. Retrospective data indicate that first-trimester use of ACE inhibitors has been associated with a potential risk of birth defects. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Infants born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. An observational cohort study evaluating the outcomes of angiotensin receptor blockers (ARBs) use during the first trimester of pregnancy found an increased rate of major birth defects compared to non-hypertensive pregnancies, 5.4% and 3%, respectively; the difference did not reach statistical significance. The authors noted that there was a higher risk of major birth defects with ARB therapy beyond 6 weeks of gestation compared to discontinuation of ARBs before week 6, 7.3% and 2.8%, respectively. The rates of prematurity and reduced birth weight were also increased in the ARB group. There were no statistically significant differences in the rates of major birth defects, spontaneous abortions, or preterm births between women with chronic hypertension treated with an ARB versus methyldopa. Thiazide diuretics can cross the placenta resulting in umbilical cord concentrations similar to maternal plasma concentrations and amniotic fluid concentrations that are up to 19 times greater than in the umbilical vein. Based on the results from one large study, first-trimester use of thiazide and related diuretics may increase the risk for congenital defects. In addition to malformations, other fetal risks associated with thiazide use during pregnancy include placental hypoperfusion, fetal or neonatal jaundice, hypoglycemia, thrombocytopenia, hyponatremia, hypokalemia, and death from maternal complications. Once pregnancy is detected, ultrasound examination should be performed if valsartan; hydrochlorothiazide exposure occurs beyond the first trimester. In rare cases, when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. Closely observe newborns with histories of in utero exposure to valsartan; hydrochlorothiazide for hypotension, oliguria, and hyperkalemia. If oliguria occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.
Breast-feeding is not recommended with valsartan; hydrochlorothiazide therapy. Limited data are available on valsartan; hydrochlorothiazide presence in breast milk, effects on milk production, or effects on the breast-fed infant. According to the manufacturer, because of the potential for adverse effects on the nursing infant, a decision should be made to discontinue breast-feeding or discontinue valsartan; hydrochlorothiazide therapy. Alternative therapies may be considered. Due to low levels in breast milk, guidelines generally consider the ACE inhibitors captopril and enalapril to be compatible with breast-feeding unless high doses are required. In addition, benazepril and quinapril are excreted in low quantities into breast milk and have been suggested as options during breast-feeding. Hydrochlorothiazide distributes into breast milk at low quantities and is usually considered compatible with breast-feeding. High hydrochlorothiazide dosages (100 mg to 150 mg/day) have been used to suppress lactation. Suppression of lactation has not been reported with hydrochlorothiazide doses of 50 mg or less. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
Safety and effectiveness of valsartan; hydrochlorothiazide have not been established in children less than 18 years old.
Hyperglycemia or impaired glucose tolerance can occur during hydrochlorothiazide therapy. In patients with diabetes mellitus who are receiving valsartan; hydrochlorothiazide, blood glucose levels should be monitored frequently. Adjustment of insulin and/or oral hypoglycemic agents may be required.
Thiazide diuretics have been reported to cause pancreatitis. Valsartan; hydrochlorothiazide should be used with caution in patients with a history of pancreatitis.
Valsartan; hydrochlorothiazide should be administered cautiously to patients with gout or hyperuricemia since thiazide diuretics such as hydrochlorothiazide have been reported to reduce the clearance of uric acid.
Hydrochlorothiazide has been reported to activate or exacerbate systemic lupus erythematosus (SLE).
Instruct patients taking hydrochlorothiazide to avoid excessive sunlight (UV) exposure and undergo regular skin cancer screening. Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer. An FDA Sentinel Initiative study found that increased risk was mostly for squamous cell carcinoma and in White patients taking large cumulative doses. The increased risk for the overall population was approximately 1 additional case per 16,000 patients per year. For White patients taking a cumulative dose more than 50,000 mg, the risk increased to approximately 1 additional case per 6,700 patients per year. Photosensitivity has been reported with thiazide diuretics.
During clinical trials of valsartan; hydrochlorothiazide, no overall difference in efficacy or safety was observed between geriatric and younger adult patients. Greater sensitivity to the usual dosage of hydrochlorothiazide or valsartan may occur in some geriatric persons, and care should be taken in initial dose selection, generally starting at the low end of the usual adult dose range. Thiazides may worsen dilutional hyponatremia, especially in geriatric individuals. An increased risk of falls has been reported for older adults receiving thiazide diuretics. Monitor renal function and for clinical signs of acid/base, fluid, or electrolyte imbalances. According to the Beers Criteria, diuretics such as hydrochlorothiazide are considered potentially inappropriate medications (PIMs) in geriatric adults and should be used with caution due to the potential for causing or exacerbating SIADH or hyponatremia. Sodium levels should be closely monitored when starting or changing dosages of diuretics.
For the treatment of hypertension:
-for initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals:
Oral dosage:
Adults: The usual starting dose is 160 mg valsartan/12.5 mg hydrochlorothiazide PO once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of valsartan 320 mg and hydrochlorothiazide 25 mg PO once daily as needed to control blood pressure. The combination product is not recommended as initial therapy in patients with intravascular volume depletion.
Geriatric: See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.
-for substitution after titration of valsartan and hydrochlorothiazide (HCTZ):
Oral dosage:
Adults: Individualize the dosage by titration of valsartan and HCTZ. The combination product (Diovan HCT) may be substituted for the individually titrated components. The dosage of 1 or both drug components may be increased after 3 to 4 weeks depending on the clinical response. The maximum dosage is 1 tablet of Diovan HCT 320 mg valsartan/25 mg HCTZ PO once daily. Correct volume and/or sodium depletion prior to administration.
Geriatric: See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.
-for patients who do not respond to monotherapy with valsartan:
Oral dosage:
Adults: A patient whose blood pressure is not adequately controlled with valsartan monotherapy may add HCTZ by switching to Diovan HCT (80 mg valsartan/12.5 mg HCTZ, 160 mg valsartan/12.5 mg HCTZ, or 320 mg valsartan/12.5 mg HCTZ) PO once daily. The dosage of 1 or both drug components may be increased after 3 to 4 weeks depending on the clinical response. The maximum dosage is 1 tablet of Diovan HCT 320 mg valsartan/25 mg HCTZ PO once daily. Correct volume and/or sodium depletion prior to administration.
Geriatric: See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.
-for patients who do not respond to monotherapy with hydrochlorothiazide (HCTZ):
Oral dosage:
Adults: A patient whose blood pressure is not adequately controlled by 25 mg PO once daily of HCTZ, or a patient who is controlled but experiences hypokalemia with this regimen, may be switched to Diovan HCT (80 mg valsartan/12.5 mg HCTZ or 160 mg valsartan/12.5 mg HCTZ) PO once daily. The dosage of 1 or both drug components may be increased after 3 to 4 weeks depending on the clinical response. The maximum dosage is 1 tablet of Diovan HCT 320 mg valsartan/25 mg HCTZ PO once daily. Correct volume and/or sodium depletion prior to administration.
Geriatric: See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.
Maximum Dosage Limits:
-Adults
320 mg/day PO valsartan and 25 mg/day PO hydrochlorothiazide.
-Geriatric
320 mg/day PO valsartan and 25 mg/day PO hydrochlorothiazide.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is necessary for patients with mild to moderate hepatic disease; however, exercise caution when dosing valsartan in patients with hepatic impairment. Mild to moderate hepatic disease is associated with a two-fold increase in valsartan AUC. No dosing recommendations are available for valsartan in patients with severe hepatic disease. HCTZ should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Patients with Renal Impairment Dosing
CrCl greater than 30 mL/min: No dosage adjustment is necessary.
CrCl 30 mL/min or less: The safety and efficacy of valsartan have not been established in adult patients. In general, loop diuretics are preferred to thiazides like hydrochlorothiazide in this population as thiazide diuretics are not effective in severe renal impairment. Use in children 6 to 16 years of age with a CrCl less than 30 mL/min/1.73 m2 has not been studied; use is not recommended.
Intermittent hemodialysis
Combination therapy with hydrochlorothiazide is not recommended in patients with CrCl 30 mL/min or less. Thiazide diuretics are generally not effective in this setting. Valsartan is not removed by hemodialysis.
*non-FDA-approved indication
Acarbose: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Acetaminophen; Aspirin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended. (Moderate) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Acetaminophen; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Acetaminophen; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Acetazolamide: (Moderate) Acetazolamide promotes electrolyte excretion including hydrogen ions, sodium, and potassium. It can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Aclidinium; Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Albuterol; Budesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alendronate; Cholecalciferol: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Aliskiren: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury.
Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury.
Allopurinol: (Moderate) Monitor renal function and for signs and symptoms of hypersensitivity and skin rash during concomitant use of allopurinol and thiazide diuretics; reduce the allopurinol dose in persons with renal impairment and concomitant thiazide diuretic use. Concomitant use may increase the risk of severe skin rash and renal impairment may further increase the risk. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity when using these drugs concomitantly.
Alogliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Alogliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Alpha-glucosidase Inhibitors: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs), may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil. (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as thiazide diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Amiloride: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Aminolevulinic Acid: (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Amlodipine; Benazepril: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Amlodipine; Celecoxib: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Amobarbital: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Amphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Amphetamine; Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Amphotericin B lipid complex (ABLC): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amphotericin B liposomal (LAmB): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Amphotericin B: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Angiotensin II: (Moderate) Angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs) may decrease the response to angiotensin II. Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure. ARBs block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the angiotensin receptor in many tissues.
Angiotensin-converting enzyme inhibitors: (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Anticholinergics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Apomorphine: (Moderate) Use of angiotensin II receptor antagonists and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination. (Moderate) Use of thiazide diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aprepitant, Fosaprepitant: (Minor) Use caution if valsartan and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of valsartan. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Valsartan is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Arformoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Arsenic Trioxide: (Moderate) Concomitant use of thiazide diuretics and arsenic trioxide should be done cautiously. Electrolyte abnormalities, such as hypokalemia and hypomagnesemia, may increase the risk for QT prolongation and torsade de pointes.
Articaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Caffeine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Aspirin, ASA; Omeprazole: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Aspirin, ASA; Oxycodone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Atazanavir: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Atazanavir; Cobicistat: (Moderate) Concurrent use of atazanavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); atazanavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together. (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Atropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Atropine; Difenoxin: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Azelastine; Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Barbiturates: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Beclomethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Benazepril: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with benzhydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Benzphetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Benztropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Beta-agonists: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Betamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bismuth Subsalicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Budesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Budesonide; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Bumetanide: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Bupivacaine; Meloxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Buprenorphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and buprenorphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Buprenorphine; Naloxone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and buprenorphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Butalbital; Acetaminophen: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Butalbital; Acetaminophen; Caffeine: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including angiotensin II receptor antagonists. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure. (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including thiazide diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcifediol: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcitriol: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Acetate: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Carbonate: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Carbonate; Simethicone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Chloride: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Gluconate: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Calcium: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Canagliflozin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant thiazide diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving thiazide diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Thiazide diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant thiazide diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving thiazide diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Thiazide diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Captopril: (Major) Discontinue the thiazide diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Carbamazepine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Cardiac glycosides: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and thiazide diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Celecoxib: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Celecoxib; Tramadol: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlordiazepoxide; Clidinium: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Chlorpromazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Cholestyramine: (Moderate) Cholestyramine, an ion exchange resin, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by up to 85% when co-administered as single doses. Although the manufacturer for Questran recommends that other medicines be taken at least 1 hour before or 4-6 hours after cholestyramine, it has been recommended that thiazides be administered at least 4 hours before or after cholestyramine to minimize the reduction in absorption. By administering hydrochlorothiazide at least 4 hours before cholestyramine, the decrease in absorption of hydrochlorothiazide is approximately 30-35%.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Chromium: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Ciclesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Cisapride: (Major) Cisapride should be used with great caution in patients receiving thiazide diuretics. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias. Serum electrolytes and creatinine should be assessed prior to administration of cisapride and whenever conditions develop that may affect electrolyte imbalance or renal function.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Citalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and citalopram use; consider discontinuing citalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Clindamycin; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
Clozapine: (Moderate) Caution is advisable during concurrent use of clozapine and thiazide diuretics as concurrent use may increase the risk and severity of hypotension. In addition, electrolyte imbalance caused by thiazide diuretics may increase the risk of QT prolongation by clozapine. (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cobicistat: (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Cod Liver Oil: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Codeine; Guaifenesin: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Codeine; Promethazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and codeine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10. (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and thiazide diuretic use. Concomitant use may result in additive hypotension.
Colestipol: (Moderate) Although to a lesser extent than cholestyramine, colestipol also has been shown to inhibit the GI absorption and therapeutic response of thiazide diuretics. Single doses of colestipol resins reduce the absorption of HCTZ by up to 43%. Administering thiazide diuretics at least 2 hours before colestipol has been suggested to minimize the interaction.
Corticosteroids: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Corticotropin, ACTH: (Minor) Monitor potassium concentrations during concomitant corticotropin and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticotropin and thiazide diuretics cause increased renal potassium loss.
Cortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with thiazide diuretics is necessary as there is an increased risk of hematologic toxicity and immunosuppression.
Cyclosporine: (Moderate) Coadministration of cyclosporine and an angiotensin II receptor antagonist, like valsartan, may increase the risk of hyperkalemia and reduced renal function. In response to cyclosporine-induced renal afferent vasoconstriction and glomerular hypoperfusion, angiotensin II is required to maintain an adequate glomerular filtration rate. Inhibition of angiotensin-converting enzyme (ACE) could reduce renal function acutely. Several cases of acute renal failure have been associated with the addition of enalapril to cyclosporine therapy in renal transplant patients. Also, cyclosporine can cause hyperkalemia, and inhibition of angiotensin II leads to reduced aldosterone concentrations, which can increase the serum potassium concentration. Closely monitor renal function and serum potassium concentrations in patients receiving cyclosporine concurrently with valsartan. Additionally, valsartan is a substrate of the hepatic uptake transporter OATP1B1 and cyclosporine is an inhibitor of OATP. Coadministration may increase systemic exposure to valsartan. Patients should be monitored for adverse effects of valsartan.
Daclatasvir: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Dapagliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Darunavir; Cobicistat: (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Deflazacort: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Desmopressin: (Moderate) Monitor serum sodium more frequently during concomitant desmopressin and thiazide diuretic use due to increased risk of water intoxication with hyponatremia.
Desvenlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Dexamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dexlansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Dexmethylphenidate: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers, hydralazine, methyldopa, minoxidil, nitrites, prazosin, reserpine, or other antihypertensive agents. (Moderate) Enhanced hyperglycemia is possible during concurrent use of diazoxide and thiazide diuretics. Additive hypotensive effects can also occur with the concomitant administration of diazoxide with thiazide diuretics.
Dichlorphenamide: (Moderate) Use dichlorphenamide and diuretics together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including loop diuretics and thiazide diuretics. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diclofenac; Misoprostol: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Dicyclomine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of thiazide diuretics. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. (Moderate) Diethylpropion has vasopressor effects and may limit the benefit of angiotensin II receptor antagonists. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Diflunisal: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Digoxin: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and thiazide diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Diphenhydramine; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Diphenoxylate; Atropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Dobutamine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly.
Dofetilide: (Contraindicated) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for dofetilide-induced torsade de pointes. Additionally, in patients treated with either hydrochlorothiazide 50 mg or hydrochlorothiazide/triamterene 50 mg/100 mg daily in combination with dofetilide 500 mcg twice daily for 5 days, dofetilide AUC and Cmax concentrations increased by 27% and 21%, respectively, for the hydrochlorothiazide alone group and by 30% and 16%, respectively, for the hydrochlorothiazide/triamterene group. Furthermore, a 197% and 190% QTc increase over time was seen in the hydrochlorothiazide and hydrochlorothiazide/triamterene groups, respectively. Based on these findings, the manufacturer of dofetilide contraindicates the concomitant use of hydrochlorothiazide (alone or in combination with other drugs such as triamterene); these findings can be explained both by an increase in the plasma concentration of dofetilide and a reduction in the serum potassium concentration. In a population pharmacokinetic analysis of plasma dofetilide concentrations, the mean dofetilide clearance of dofetilide was 16% lower in patients on thiazide diuretics. It is prudent to avoid the use of any thiazide diuretic in combination with dofetilide.
Dolasetron: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Donepezil; Memantine: (Minor) Memantine reduced the bioavailability of hydrochlorothiazide by roughly 20% in a drug interaction study. The clinical significance of this pharmacokinetic interaction, if any, is unknown.
Dopamine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly.
Doxercalciferol: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with thiazide diuretics which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Estetrol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Ethinyl Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Duloxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for valsartan-related adverse reactions (i.e., hypotension) during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of valsartan. Valsartan is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
Eltrombopag: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer. (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer. (Minor) Caution is warranted when cobicistat is administered with valsartan as there is a potential for increased valsartan concentrations. Valsartan is a substrate of organic anion transporting polypeptide (OATP)1B1. Cobicistat is an inhibitor of OATP.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Empagliflozin; Linagliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Empagliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Enalapril, Enalaprilat: (Major) Discontinue the thiazide diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and angiotensin II receptor antagonists (ARBs). Hyperkalemia risk is increased when eplerenone is used with ARBs. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations.
Epoprostenol: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Escitalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Esomeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness. (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethacrynic Acid: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Ethanol: (Major) Advise patients to avoid alcohol while taking thiazide diuretics. Ingesting alcohol can increase the risk for orthostatic hypotension when taking a thiazide diuretic.
Ethiodized Oil: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Etodolac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as valsartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of valsartan during coadministration with fenofibric acid.
Fenoprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fentanyl: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and fentanyl; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Flavoxate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Fluconazole: (Moderate) Monitor for fluconazole-related adverse events during concomitant hydrochlorothiazide use. Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45% +/- 31% and 43% +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%.
Fludrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Flunisolide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Fluocinolone; Hydroquinone; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Fluphenazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Flurbiprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Fluticasone; Salmeterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluticasone; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fluvoxamine: (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia.
Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Formoterol; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Fosinopril: (Major) Discontinue the thiazide diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Furosemide: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Gemfibrozil: (Minor) Coadministration of valsartan and gemfibrozil may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and gemfibrozil is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glipizide; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glyburide; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Glycopyrrolate; Formoterol: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Granisetron: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Guaifenesin; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Heparin: (Minor) Concomitant use of valsartan with other drugs that may increase potassium concentrations, such as heparin, may lead to increases in serum potassium.
Homatropine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Discontinue the thiazide diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Hydrocodone; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and hydrocodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Hydrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hyoscyamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Famotidine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Oxycodone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Icosapent ethyl: (Moderate) Thiazide diuretics may exacerbate hypertriglyceridemia and should be discontinued or changed to alternate therapy, if possible, prior to initiation of icosapent ethyl.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Indacaterol; Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. In some patients, this may be desirable, but orthostatic hypotension may occur. Angiotensin II receptor antagonists tend to reverse the potassium loss, but not the serum uric acid rise associated with thiazide diuretic monotherapy.
Indomethacin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Iodixanol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iohexol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iomeprol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iopamidol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iopromide: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Ioversol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Ipratropium; Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when isocarboxazid is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of isocarboxazid with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of isocarboxazid and an angiotensin II receptor antagonist. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
Isoniazid, INH; Rifampin: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Isosulfan Blue: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ketoprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ketorolac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Lansoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Levalbuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Levomilnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Linagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Linagliptin; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Lisdexamfetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Lisinopril: (Major) Discontinue the thiazide diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Lithium: (Moderate) Monitor lithium concentrations during concomitant use with thiazide diuretics; consider lower lithium starting doses and titrating slowly while frequently monitoring lithium concentrations and for signs of lithium toxicity. Thiazide diuretics reduce the renal clearance of lithium and increase the risk for lithium toxicity. (Moderate) Monitor serum lithium concentrations during concomitant angiotensin II receptor blocker use; reduce the lithium dose based on serum lithium concentration and clinical response. Concomitant use may increase steady-state lithium concentrations.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Loop diuretics: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Lopinavir; Ritonavir: (Moderate) Concurrent use of lopinavir with valsartan may result in elevated valsartan serum concentrations. Valsartan is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); lopinavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together. (Minor) Valsartan is a substrate of the hepatic efflux transporter MRP2 and ritonavir is an inhibitor of MRP2. Coadministration may increase systemic exposure to valsartan. Patients should be monitored for adverse effects of valsartan during coadministration.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Magnesium Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
Meclofenamate Sodium: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Mefenamic Acid: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Meglitinides: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Meloxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Memantine: (Minor) Memantine reduced the bioavailability of hydrochlorothiazide by roughly 20% in a drug interaction study. The clinical significance of this pharmacokinetic interaction, if any, is unknown.
Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Metaproterenol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Metformin; Saxagliptin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Metformin; Sitagliptin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Methadone: (Moderate) Diuretics can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed. In addition, opiate agonists may potentiate orthostatic hypotension when used concurrently with diuretics.
Methamphetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. (Minor) Methamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) Thiazide diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
Methenamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Methenamine; Sodium Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methohexital: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methotrexate: (Moderate) Monitor for increased methotrexate-related adverse reactions during concomitant thiazide diuretic use. Thiazide diuretics may decrease renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Methoxsalen: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound.
Methscopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methylphenidate: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methylprednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Metoclopramide: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
Midodrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Miglitol: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Milnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mirtazapine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and mirtazapine use; consider discontinuing mirtazapine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Moexipril: (Major) Discontinue the thiazide diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Morphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Morphine; Naltrexone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Nabumetone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen; Esomeprazole: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Nateglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary. (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring is recommended. Dependent upon clinical response, dosage adjustments of either drug may be necessary.
Neostigmine; Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents. (Moderate) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nirmatrelvir; Ritonavir: (Minor) Valsartan is a substrate of the hepatic efflux transporter MRP2 and ritonavir is an inhibitor of MRP2. Coadministration may increase systemic exposure to valsartan. Patients should be monitored for adverse effects of valsartan during coadministration.
Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure. (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Norepinephrine: (Moderate) Thiazide diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration.
Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Olopatadine; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Omeprazole; Sodium Bicarbonate: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and thiazide diuretic use due to risk for hypomagnesemia.
Oritavancin: (Moderate) Valsartan is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated valsartan plasma concentrations. If these drugs are administered concurrently, blood pressure should be monitored closely.
Oxaprozin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Oxybutynin: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and oxycodone; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. If these drugs are used together, closely monitor for changes in blood pressure. (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and angiotensin II receptor antagonists who are susceptible to hypotension. (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and thiazide diuretics who are susceptible to hypotension.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Pantoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant pantoprazole and thiazide diuretic use due to risk for hypomagnesemia.
Paricalcitol: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Paroxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Pasireotide: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Pentamidine: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as thiazide diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. Closely monitor serum electrolytes during pentamidine therapy.
Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentobarbital: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perindopril: (Major) Discontinue the thiazide diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Perindopril; Amlodipine: (Major) Discontinue the thiazide diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Perphenazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Perphenazine; Amitriptyline: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Phendimetrazine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phenelzine: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenelzine use due to risk for additive hypotension.
Phenobarbital: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Phenothiazines: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Phentermine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phentermine; Topiramate: (Moderate) Monitor serum potassium concentrations and for increased topiramate-related adverse effects during concomitant hydrochlorothiazide use. Concomitant use has been shown to increase topiramate exposure by 29% and may potentiate the potassium-wasting action of hydrochlorothiazide. (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly.
Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Photosensitizing agents (topical): (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Pioglitazone; Metformin: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Piroxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Polycarbophil: (Moderate) Coadministration may lead to hypercalcemia because thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium polycarbophil is used concomitantly, monitoring of serum calcium may be prudent.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Porfimer: (Major) Avoid coadministration of porfimer with thiazide diuretics due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction.
Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Pramlintide: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of pramlintide by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with pramlintide should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Prazosin: (Moderate) Monitor blood pressure during concomitant use of prazosin and angiotensin II receptor blockers (ARBs). Concomitant use may produce additive hypotension and increase the risk for syncope. The risk for significant hypotension and syncope is greatest when adding an antihypertensive to a regimen that includes high dose prazosin and following a rapid dosage increase. To minimize the risk for adverse effects, consider reducing the prazosin dose to 1 to 2 mg three times a day during initiation of a new antihypertensive and then retitrating prazosin based on clinical response. (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Prednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Prednisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Primidone: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Probenecid: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Probenecid; Colchicine: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects. (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Prochlorperazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Promethazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Promethazine; Phenylephrine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Propantheline: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure.
Pyridoxine, Vitamin B6: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Quinapril: (Major) Discontinue the thiazide diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the thiazide diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rabeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Ramipril: (Major) Discontinue the thiazide diuretic prior to starting ramipril, if possible, or start ramipril at a lower dose to minimize hypotension. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when rasagiline is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during coadministration. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and angiotensin II receptor blocker use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes.
Remifentanil: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Rifampin: (Minor) Coadministration may increase systemic exposure to valsartan. Valsartan is a substrate of the hepatic uptake transporter OATP1B1 and rifampin is an inhibitor of OATP. Patients should be monitored for adverse effects of valsartan.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly. (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ritonavir: (Minor) Valsartan is a substrate of the hepatic efflux transporter MRP2 and ritonavir is an inhibitor of MRP2. Coadministration may increase systemic exposure to valsartan. Patients should be monitored for adverse effects of valsartan during coadministration.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Salicylates: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Salmeterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Salsalate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Saxagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Scopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Secobarbital: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Monitor blood pressure and adjust the dose of the angiotensin II blockers as needed during coadministration with methylphenidate. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and methylphenidate use; a thiazide diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sertraline: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and sertraline use; consider discontinuing sertraline if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk. (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of valsartan, an Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3) substrate, may be increased when administered concurrently with voxilaprevir, an OATP1B1/1B3. Monitor patients for changes in blood pressure and increased side effects if these drugs are administered concurrently.
Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sparsentan: (Contraindicated) Concomitant use of sparsentan and angiotensin receptor blockers (ARBs) is contraindicated due to the additive risk for serious adverse effects such as hypotension, syncope, hyperkalemia, and renal dysfunction.
Spironolactone: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Sulfacetamide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics.
Sulfacetamide; Sulfur: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Sulindac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Sumatriptan; Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tegaserod: (Minor) Coadminisitration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
Terbutaline: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Thioridazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tiotropium; Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and tizanidine use due to risk for additive hypotension.
Tolmetin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Tolvaptan: (Moderate) Monitor serum potassium concentrations closely if tolvaptan and angiotensin II receptor blockers are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with angiotensin II receptor blockers compared to administration of these medications with placebo. (Moderate) Monitor serum sodium closely if tolvaptan and thiazide diuretics are used together. Coadministration increases the risk of too rapid correction of serum sodium.
Topiramate: (Moderate) Monitor serum potassium concentrations and for increased topiramate-related adverse effects during concomitant hydrochlorothiazide use. Concomitant use has been shown to increase topiramate exposure by 29% and may potentiate the potassium-wasting action of hydrochlorothiazide.
Toremifene: (Moderate) Monitor serum calcium levels in patients receiving concomitant treatment with toremifene and thiazide diuretics. Thiazide diuretics decrease renal calcium excretion and may increase the risk of hypercalcemia in patients receiving toremifene.
Torsemide: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Tramadol: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Tramadol; Acetaminophen: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and tramadol; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic.
Trandolapril: (Major) Discontinue the thiazide diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Trandolapril; Verapamil: (Major) Discontinue the thiazide diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure, particularly when doses are increased, and renal function during concomitant use. Concomitant use may increase the risk for hypotension or renal failure. (Major) In general, avoid combined use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) due to lack of benefit with concomitant use in most patients. Closely monitor blood pressure, renal function, and electrolytes in patients on ACE inhibitors and ARBs. Dual blockade of the renin-angiotensin system with ACE inhibitors and ARBs is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function, including acute renal failure, compared to monotherapy.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Treprostinil: (Moderate) Thiazide diuretics can enhance the hypotensive effects of antihypertensive agents or diuretics if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly.
Tretinoin, ATRA: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tretinoin; Benzoyl Peroxide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Triamcinolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Triamterene: (Moderate) Monitor serum potassium concentrations in patients receiving angiotensin II receptor antagonists concomitantly with triamterene. Concomitant use may result in hyperkalemia.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations in patients receiving angiotensin II receptor antagonists concomitantly with triamterene. Concomitant use may result in hyperkalemia.
Trifluoperazine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Trihexyphenidyl: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Trimethoprim: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Umeclidinium; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Venlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with thiazide diuretics is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction.
Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
Vitamin B Complex Supplements: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Vitamin D analogs: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Vorinostat: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia.
Zafirlukast: (Minor) In vitro data indicate that zafirlukast inhibits the CYP2C9 and CYP3A4 isoenzymes at concentrations close to the clinically achieved total plasma concentrations. Until more clinical data are available, zafirlukast should be used cautiously in patients stabilized on drugs metabolized by CYP2C9 such as valsartan.
Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Ziprasidone: (Moderate) Monitor potassium and magnesium levels when thiazide diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia. (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
The effects of valsartan and hydrochlorothiazide on blood pressure are additive. Thiazide diuretics lower the blood pressure by increasing the excretion of sodium; whereas valsartan lowers blood pressure by selectively blocking the AT1 receptor to antagonize the actions of angiotensin II, the primary vasoactive hormone of the renin-angiotensin system. Valsartan tends to reverse the hypokalemia caused by the hydrochlorothiazide.
-Valsartan: Valsartan antagonizes angiotensin II at the AT1 receptor subtype. Two angiotensin II receptors, AT1 and AT2, have been identified. While valsartan has about a 20,000-fold greater affinity for the AT1 subtype than the AT2 subtype, the AT2 subtype is not known to mediate cardiovascular homeostasis. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of hypertension and congestive heart failure. Angiotensin II is a potent vasoconstrictor; which also stimulates the synthesis and release of aldosterone. By selectively blocking the AT1 receptor in tissues such as vascular smooth muscle and the adrenal gland, valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. Thus, by blocking the effects of angiotensin II, valsartan decreases systemic vascular resistance without a marked change in heart rate. Circulating levels of both renin and angiotensin II rise 2- to 3-fold in response to blockade of AT1 receptors. Because valsartan does not inhibit ACE, it also does not inhibit the breakdown of bradykinin. Unlike losartan, valsartan has no effect on serum uric acid.
-Hydrochlorothiazide: Thiazides increase the excretion of water by inhibiting the reabsorption of sodium and chloride ions at the distal renal tubule. The natriuretic effects are accompanied by a secondary loss of potassium and bicarbonate which can cause a mild hypokalemic, hypochloremic, metabolic alkalosis. Thiazides also decrease the elimination of calcium and uric acid. Thiazides diuretics usually do not affect normal blood pressure. When chronically administered, diuretics decrease peripheral vascular resistance. The exact mechanism responsible for the lowered peripheral resistance is not known; however, excretion of urinary sodium by the kidneys is required to achieve blood pressure reduction. Initially, diuretics lower blood pressure by decreasing cardiac output, plasma volume and extracellular fluid volume. Cardiac output eventually returns to normal, plasma and extracellular fluid values return to slightly less than normal, but peripheral vascular resistance is reduced, resulting in lower blood pressure. Thiazide diuretics also decrease the glomerular filtration rate, which contributes to the drug's lower efficacy in patients with renal impairment. The changes in plasma volume induce an elevation in plasma renin activity and aldosterone secretion which contributes to the potassium losses associated with thiazide diuretics. In general, diuretics can worsen glucose tolerance and lipid abnormalities.
Valsartan; hydrochlorothiazide is administered orally. No pharmacokinetic drug interaction is observed between valsartan and hydrochlorothiazide.
-Valsartan: Approximately 95% of valsartan is bound to serum proteins, primarily albumin. In animal studies, valsartan did not readily penetrate the blood brain barrier. Valsartan is not a prodrug. The primary metabolite of valsartan is valeryl-4-hydroxy valsartan, which is inactive and accounts for about 9% of the dose. In vitro studies indicate CYP 2C9 is the isoenzyme responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan is not an inhibitor of CYP 450 isoenzymes at clinically relevant concentrations. Valsartan is excreted primarily in the feces, most likely via the biliary route of elimination. Only 10% of the dose is excreted unchanged in urine. The elimination half-life (half-life) of valsartan averages 6 hours. Abrupt withdrawal of valsartan has not been associated with a rapid increase in blood pressure.
-Hydrochlorothiazide: Hydrochlorothiazide binds to albumin (40 to 70%) and distributes into erythrocytes. The drug crosses the placenta, but not the blood-brain barrier, and is distributed into breast milk. Hydrochlorothiazide is not significantly metabolized. About 70% of an orally administered dose is excreted unchanged in the urine. The mean distribution half-life is about 2 hours and the elimination half-life is about 10 hours.
-Route-Specific Pharmacokinetics
Oral Route
-Valsartan: Valsartan is administered orally. It is rapidly absorbed, with peak plasma concentrations occurring 2 to 4 hours after administration. Absolute bioavailability for the capsule formulation is roughly 25% (range, 10% to 35%). Administration with food decreases the AUC by about 40%; therapeutic effect is maintained despite the reduction in bioavailability. AUC and Cmax increase linearly within the dosage range of 80 to 320 mg; however, the antihypertensive dose-response curve is nonlinear, with proportionally small decreases in blood pressure attained with increased dosage. Duration of antihypertensive activity is approximately 24 hours, allowing for once daily dosing. An oral dose of valsartan 80 mg inhibits the pressor effect of angiotensin II by about 80% at peak serum concentrations, with 30% inhibition persisting for 24 hours. Onset and peak effect of antihypertensive activity is 2 hours and 6 hours, respectively. Maximum reduction in blood pressure is generally achieved after 4 weeks with chronic dosing.
-Hydrochlorothiazide: Following oral administration, hydrochlorothiazide absorption from the GI tract varies depending on the formulation, dose, and presence of concomitant disease states. Absorption is reduced in patients with hepatic, cardiac, and/or renal disease. The bioavailability is approximately 60% to 70%. The onset of action is 2 hours following oral administration, with peak effects occurring at 4 hours. The duration of action ranges from 6 to 12 hours.
-Special Populations
Hepatic Impairment
-Valsartan: Patients with mild-moderate chronic hepatic disease have a two-fold increase in the AUC of valsartan, but in general, caution is advised and no dosage adjustment is needed. There are no data in patients with severe liver disease.
-Hydrochlorothiazide: Absorption is reduced in patients with hepatic disease.
Renal Impairment
-Valsartan: The elimination half-life of valsartan is not significantly affected by mild to moderate renal impairment, but safety and efficacy have not been established in adult patients with CrCl less than 30 mL/min. Data for adult patients with severe renal impairment (CrCl less than 10 mL/min) are not available. Use in children 6 to 16 years of age with a CrCl less than 30 mL/min/1.73 m2 has not been studied; use is not recommended. Valsartan is not removed by hemodialysis.
-Hydrochlorothiazide: Absorption is reduced in patients with renal disease. Results from a study evaluating the pharmacokinetics of hydrochlorothiazide in relation to renal function indicate the elimination half life increases with varying degrees of renal failure, from 6.4 hours for patients with normal renal function to 11.5 hours for patients with mild renal impairment (30 to 90 mL/min) to 20.7 hours in patients with CrCl less than 30 mL/min.
Pediatrics
-Valsartan: In pharmacokinetic study, the clearance of single dose valsartan is similar in adult and pediatric (1 to 16 years of age) subjects. Use in children 6 to 16 years of age with a CrCl less than 30 ml/min/1.73 m2 has not been studied; use is not recommended.
Geriatric
-Valsartan: Compared to younger subjects, the AUC and half-life are increased by 70% and 35%, respectively in geriatric patients.
-Hydrochlorothiazide: Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive geriatric patients compared to young healthy volunteers.
Other
Cardiac Disease
-Hydrochlorothiazide: Absorption is reduced in patients with cardiac disease.