Lisinopril is an oral angiotensin-converting enzyme (ACE) inhibitor used in the treatment of hypertension, congestive heart failure, post-myocardial infarction, and diabetic nephropathy or retinopathy. Chemically, it is the lysine ester of enalaprilat, the active moiety of enalapril. Unlike enalapril, lisinopril is not a prodrug and does not require metabolic activation. Unlike captopril, lisinopril does not contain a sulfhydryl group, which has been implicated in a distinctive adverse reaction profile including skin rash and taste disturbance. Lisinopril also has a slower onset and a longer duration of action than either captopril or enalapril; this enables lisinopril to be dosed once daily, which may improve compliance. In general, ACE inhibitors appear to have a lesser effect on blood pressure in Black patients (low renin population) than in non-Black patients; a higher initial dose or alternative initial therapy (e.g., thiazide diuretic, long-acting calcium channel blocker) may be considered in this population.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May administer without regard to food.
Oral Liquid Formulations
-Measure with a calibrated oral syringe prior to administration.
Extemporaneous Compounding-Oral
NOTE: There is an FDA-approved oral solution of lisinopril (1 mg/mL) commercially available.
Extemporaneous preparation of 1 mg/mL lisinopril oral suspension:
-Crush five (5) lisinopril 20 mg tablets in a mortar and grind to a fine powder.
-Add a small quantity of Ora-Plus and mix to form a smooth paste.
-Add the remainder of the 50 mL Ora-Plus in geometric proportions and mix well.
-Add Ora-Sweet quantity sufficient to make a final volume of 100 mL and mix well.
-Shake well prior to each administration.
-Storage: Stable at room temperature for 90 days.
Extemporaneous preparation of 2 mg/mL lisinopril oral suspension:
-Crush forty-eight (48) 5 mg tablets in a mortar and grind to a fine powder.
-Measure out 20 mL of distilled water in a graduated cylinder.
-Wet the powder with the smallest amount of distilled water as possible, forming a smooth uniform paste.
-Add the remaining distilled water and Simple Syrup vehicle geometrically until a volume slightly short of 120 mL, mixing well.
-Transfer the suspension to a graduated cylinder.
-Rinse the mortar with vehicle and add rinse to the graduated cylinder.
-Add Simple Syrup quantity sufficient to make a final volume of 120 mL.
-Shake well prior to each administration.
-Storage: Stable at room temperature or refrigerated for 30 days.
Adverse reactions associated with the use of lisinopril are usually mild and transient. Based on the ATLAS study of 3,164 congestive heart failure patients, the high dose (32.5 to 35 mg/day) group of the ATLAS study had more adverse effects compared to the low dose group (2.5 to 5 mg/day), but there was no difference in the withdrawal rate due to adverse effects (17% to 18%).
Hypotension has been reported in 4% to 11% of lisinopril-treated patients. In the ATLAS study, hypotension was reported more frequently in the high dose vs. low dose groups (11% vs. 7%, respectively). Patients with acute MI in the GISSI-3 trial had a higher (9% vs. 4%) incidence of persistent hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour) when treated with lisinopril. Monitor patients closely during treatment initiation and dose escalation.
Chest pain (unspecified) was reported in 2% of lisinopril-treated adult patients with heart failure during clinical trials.
Dizziness (4% to 19%) and headache (4%) were among the most commonly reported adverse reactions associated with the use of lisinopril in adult clinical trials. Orthostatic hypotension was reported in 1% or more of lisinopril-treated patients. In the ATLAS study, dizziness (19% vs. 12%) and syncope (7% vs. 5%) were reported more frequently in the high dose vs. low dose groups, respectively.
Cough has been reported in approximately 3% of lisinopril-treated adult patients in clinical trials. ACE inhibitor use is often associated with a dry, hacking, nonproductive cough that typically develops 1 to 2 weeks after, but may occur within hours to months after, treatment initiation. The only uniformly effective intervention is cessation of the offending agent, which should occur only after other causes (e.g., pulmonary congestion) are ruled out; cessation typically results in resolution within 1 to 4 weeks. Although the mechanism of ACE inhibitor-induced cough is unclear, it likely involves bradykinin and substance P, which are degraded by ACE and therefore accumulate in the respiratory tract with enzyme inhibition, and prostaglandins, the production of which may be stimulated by bradykinin.
Anaphylactoid reactions and angioedema are uncommon but serious and potentially fatal adverse reactions associated with ACE inhibitor use. Angioedema may manifest as swelling of the face, lips, tongue, glottis, larynx (laryngeal edema), extremities, or, in rare cases, edema of the gastrointestinal tract. Angioedema of the upper respiratory tract can result in airway obstruction and acute respiratory distress, especially in those with a history of airway surgery. Intestinal angioedema presents as abdominal pain with or without nausea and vomiting. In some cases, patients with intestinal involvement had no prior history of facial angioedema and C-1 esterase levels were normal; intestinal angioedema was diagnosed by procedures such as abdominal CT scan or ultrasound or during surgery. Angioedema usually occurs within hours to days of treatment initiation, but may occur at any time during treatment. Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-Black patients. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. If a hypersensitivity reaction occurs, promptly discontinue lisinopril and provide appropriate and aggressive treatment and monitoring until complete and sustained resolution has occurred. Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors who present with pain in the abdomen.
Fatigue and asthenia were reported in 1% or more of lisinopril-treated adult patients with hypertension or heart failure during clinical trials. Mood alterations (including symptoms of depression), mental confusion, and hallucinations have been reported with postmarketing use of lisinopril.
Visual impairment (vision loss), diplopia, blurred vision, tinnitus, photophobia, dysgeusia, and dysosmia have been reported in 1% or more of lisinopril-treated patients with hypertension or heart failure in controlled clinical trials. Dysgeusia is a fairly common but often ignored adverse effect of ACE inhibitors. Taste disturbances range from persisting sweetness or saltiness to bitter or metallic taste and appear to be most commonly associated with captopril, which has a sulfhydryl group. However, increased local bradykinin concentrations have also been implicated in taste related symptoms. If dysgeusia occurs, encourage the patient to improve oral hygiene. Masking methods such as chewing sugarless gum or sucking on ice chips may help reduce symptoms. Changes in taste such as loss in salt or sweet perception may have nutritional implications, particularly for patients with hypertension, heart disease, and diabetes.
Gastrointestinal adverse reactions reported in 1% or more of lisinopril-treated patients during controlled-clinical trials include diarrhea, constipation, flatulence, pancreatitis, and xerostomia. Hepatotoxicity (hepatitis, hepatic failure) has been reported in patients receiving ACE inhibitors. Although not completely understood, hepatotoxicity has included cholestasis with jaundice, fulminant hepatic necrosis, and death. Discontinue lisinopril and institute appropriate treatment in patients who develop jaundice or markedly elevated hepatic enzymes during therapy.
Dermatologic adverse reactions reported in 1% or more of lisinopril-treated patients in controlled clinical trials include pruritus, urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, and Stevens-Johnson Syndrome. Psoriasis has been reported with postmarketing use.
A symptom complex which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, leukocytosis, paresthesias, and vertigo has been reported in association with lisinopril use. Rash, photosensitivity, or other dermatological manifestations may occur alone or in combination with these symptoms.
Small decreases in hemoglobin and hematocrit occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia; less than 0.1% of patients discontinued therapy due to anemia. Rare cases of bone marrow depression, hemolytic anemia, leukopenia, neutropenia and thrombocytopenia were reported in 1% or more of lisinopril-treated patients with hypertension or heart failure in controlled clinical trials. Agranulocytosis has been associated with ACE inhibitor use, and appears to occur more frequently in patients with renal impairment or collagen vascular disease. If lisinopril is used in patients with impaired renal function or autoimmune disease, monitor a complete blood cell count with differential prior to initiation and periodically throughout therapy. Instruct patients to report any signs of infection. If infection is suspected, evaluate blood counts immediately.
Treatment with ACE inhibitors has been associated with oliguria, progressive azotemia, and rarely acute renal failure (unspecified) and death, most often in patients whose renal function depends in part on the activity of the renin-angiotensin-aldosterone system (e.g., those with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction, or volume depletion). During the ATLAS trial, increased serum creatinine was reported in 7% to 10% of lisinopril-treated adult patients with heart failure. Minor increases in blood urea nitrogen (BUN) and serum creatinine, reversible upon drug discontinuation, were observed in 2% of adult patients with hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in those with renal artery stenosis. Reversible minor increases in BUN and serum creatinine were observed in 12% of adult patients with heart failure on concomitant diuretic therapy; these elevations frequently resolved when the diuretic dose was decreased. Adult patients with acute myocardial infarction who were treated with lisinopril had a higher incidence of renal dysfunction (2%) compared to those receiving placebo (1%). Monitor renal function periodically and consider withholding or discontinuing lisinopril treatment in patients who develop a significant decrease in renal function during use. If oliguria or significant hypotension occurs, support renal perfusion.
Endocrine/metabolic-related adverse reactions occurring in 1% or more of lisinopril-treated patients with hypertension or heart failure in controlled clinical trials include diabetes mellitus, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and gout. Advise diabetic patients taking oral antidiabetic agents or insulin to monitor blood glucose closely, especially during the first month of combined use. Cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin have been reported in postmarketing experience.
Due to the potential for teratogenesis, lisinopril should not be used during pregnancy. 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, renal failure, oligohydramnios, and death. Oligohydramnios has been associated with fetal lung hypoplasia and skeletal deformations. If oliguria or hypotension occurs in a neonate with a history of in utero exposure to lisinopril, 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. Lisinopril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.
Hyperkalemia (serum potassium more than 5.7 mEq/L) occurred in approximately 2% and 5% of lisinopril-treated adult patients with hypertension and heart failure, respectively, during clinical trials. In the ATLAS trial of adult patients with heart failure, hyperkalemia occurred more frequently in the high dose lisinopril group (6%) compared with the low dose group (4%). Monitor serum potassium at baseline and periodically in all patients receiving lisinopril and correct pre-existing hyperkalemia prior to initiation. Advise patients not to use salt substitutes containing potassium. Hyponatremia has also been reported with postmarketing use.
Impotence (erectile dysfunction) was reported in 1% or more of lisinopril-treated patients in controlled clinical trials.
Lisinopril is contraindicated in patients with a history of angiotensin-converting enzyme inhibitors (ACE inhibitors) hypersensitivity, ACE-inhibitor induced angioedema, hereditary angioedema, or idiopathic angioedema. Risk of angioedema may also be higher in patients with a history of angioedema unrelated to ACE inhibitors. ACE inhibitor hypersensitivity usually manifests as a result of alterations in kinin generation in sensitive individuals; there is no evidence of a specific immune-mediated reaction. However, such reactions can be potentially life-threatening, even if they are not true 'allergic' reactions. If angioedema occurs, promptly discontinue ACE inhibitor therapy and provide appropriate treatment and monitoring until complete and sustained resolution has occurred. The incidence of ACE-inhibitor induced angioedema is higher in Black patients than non-Black patients. In addition, ACE inhibitors are less effective in lowering blood pressure in Black patients. Hence, a higher initial dose for the ACE inhibitor or alternative initial therapy with a thiazide diuretic or long-acting calcium channel blocker may be considered in Black patients with hypertension.
Monitor serum potassium at baseline and periodically in all patients receiving lisinopril and correct pre-existing hyperkalemia prior to initiation. ACE inhibitors can elevate serum potassium concentrations. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, and/or other drugs that may increase serum potassium.
Use lisinopril with caution in patients with collagen-vascular disease (e.g., systemic lupus erythematosus (SLE) or scleroderma) or in those with pre-existing bone marrow suppression, particularly when there is also renal impairment. ACE inhibitors, specifically captopril, have been associated with neutropenia and agranulocytosis. In clinical trials for captopril, neutropenia rarely occurred in uncomplicated patients and was more common in patients with renal impairment, particularly if the patient also had collagen-vascular autoimmune disease or was receiving concomitant immunosuppression. If lisinopril is used in patients with impaired renal function or autoimmune disease, monitor a complete blood cell count with differential prior to initiation and periodically throughout therapy. Instruct patients to report any signs of infection. If infection is suspected, evaluate blood counts immediately. Neutropenia has usually been detected within 3 months after ACE inhibitor initiation.
Anaphylactoid reactions have been reported in patients taking ACE inhibitors, such as lisinopril, who were receiving dialysis with high-flux membranes (e.g., AN69). If an anaphylactoid reaction occurs, stop dialysis immediately and initiate aggressive treatment for the hypersensitivity reaction; antihistamine therapy may not be sufficient. Consider an alternative dialysis membrane or an alternative medication in patients with a history of reaction. Anaphylactoid reactions have also occurred in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. ACE inhibitors may precipitate low blood pressure in patients requiring extracorporeal procedures, particularly if the patient is volume-depleted. Treatment with ACE inhibitors may also increase the risk of anaphylactoid reactions in patients undergoing hymenoptera venom (insect sting) allergy desensitization. Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon rechallenge. However, a retrospective analysis of 79 patients who underwent hymenoptera venom (insect sting) allergy desensitization did not show an association between ACE inhibitor therapy and increased frequency of systemic reactions to venom immunotherapy. Of the 17 patients taking an ACE inhibitor while undergoing desensitization, none experienced a systemic reaction to venom immunotherapy; comparatively, 13 of 62 patients not taking an ACE inhibitor experienced a systemic reaction during venom immunotherapy.
Use lisinopril with caution in patients at risk for excessive hypotension, including those with ischemic heart disease, aortic stenosis, hypertrophic cardiomyopathy, cerebrovascular disease, hyponatremia, hypovolemia, and those receiving high dose diuretic therapy or dialysis. Patients with heart failure, particularly those with a systolic blood pressure below 100 mmHg, are at risk for hypotension and should be initiated on a lower dose of lisinopril compared to those patients being treated for hypertension. Correct volume depletion prior to initiation. Monitor patients closely during the first 2 weeks of treatment and whenever the dose of lisinopril (and/or diuretic) is increased. Dose reduction and careful titration may be necessary. Avoid lisinopril use in hemodynamically unstable patients after an acute myocardial infarction. Hypotension may aggravate ischemia in patients with coronary artery disease or cerebrovascular disease precipitating a myocardial infarction or cerebrovascular accident. Patients with severe heart failure, post-myocardial infarction, or volume depletion may also be at risk for developing renal dysfunction.
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril may block angiotensin II formation secondary to compensatory renin release. Hypotension considered to be due to this mechanism can be corrected by volume expansion.
ACE inhibitors, such as lisinopril, have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Discontinue lisinopril in patients who develop jaundice or marked elevations of hepatic enzymes during therapy and institute appropriate medical treatment.
Lisinopril can cause fetal harm when administered to a pregnant patient. Once pregnancy is detected, discontinue lisinopril therapy as soon as possible. Women of child-bearing age should be made aware of the potential risk and lisinopril should only be given after careful counseling and consideration of individual risks and benefits. When used during the second and third trimesters, medications that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal 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, and reversible or irreversible renal failure. 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. 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. If oligohydramnios is observed, discontinue lisinopril unless it is considered life-saving for the mother. Oligohydramnios may not appear until after the fetus has sustained an irreversible injury. Closely observe neonates with histories of in utero exposure to lisinopril for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension 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.
No data are available regarding the presence of lisinopril in human milk or the effects of lisinopril on the breastfed infant or on milk production. Lisinopril is present in rat milk. Because of the potential for severe adverse reactions in the breastfed infant, the manufacturer's advise women to discontinue breast-feeding during treatment with lisinopril. Alternative therapies may be considered. Due to low levels in breast milk, guidelines generally consider 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
For unknown reasons, neonates and infants have an increased sensitivity to ACE inhibitors which makes them susceptible to prolonged or excessive decreases in blood pressure. It has been theorized this may be due to higher renin concentrations in the first few months of life and an increased dependence on the renin-angiotensin system and/or decreased drug clearance due to immature elimination systems.
No dosage adjustment with lisinopril is necessary in geriatric adults. In a clinical study of lisinopril in patients with myocardial infarctions (GISSI-3 Trial), 4,413 (47%) were 65 years of age and older, while 1,656 (18%) were 75 years of age and over. In this study, 4.8% of patients 75 years of age and older discontinued lisinopril treatment because of renal dysfunction vs. 1.3% of those younger than 75 years. No other differences in safety or effectiveness were observed between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Deterioration of renal function and renal impairment can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function is dependent on the activity of the renin-angiotensin system, including those with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction, or volume depletion, may be at risk for developing acute renal failure with lisinopril use. Monitor renal function periodically and consider withholding or discontinuing lisinopril treatment in patients who develop a significant decrease in renal function during use. Treatment with ACE inhibitors has demonstrated favorable effects on the progression of renal disease in diabetic and nondiabetic patients; however, minor increases in BUN and serum creatinine may occur. These effects, more commonly reported in patients with renal artery stenosis or those receiving concomitant diuretic therapy, are usually reversible and are not considered a reason to withhold therapy unless accompanied by hyperkalemia. If lisinopril is initiated in patients with renal artery stenosis, monitor renal function during the first few weeks of therapy. Dosage adjustment of lisinopril is recommended in adult patients with moderate to severe renal impairment (i.e., CrCl 30 mL/minute or less). The FDA-approved labeling does not recommend use in pediatric patients with a glomerular filtration rate (GFR) less than 30 mL/minute/m2, although dosage adjustment recommendations for pediatric patients with a GFR of 50 mL/minute/1.73 m2 or less are available.
For the treatment of hypertension:
Oral dosage:
Adults: 10 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 10 to 40 mg/day. Max: 80 mg/day.
Children and Adolescents 6 to 17 years: 0.07 mg/kg/dose (Max: 5 mg/dose) PO once daily, initially. May increase dose if further control is needed. Max: 0.6 mg/kg/day (Max: 40 mg/day).
Children 2 to 5 years*: Limited data available. 0.07 to 0.1 mg/kg/dose PO once daily, initially. May increase dose if further control is needed. Max: 0.6 mg/kg/day. An initial dose of 0.1 mg/kg PO once daily, adjusted according to clinical response (Max: 0.5 mg/kg/day) was reported in a retrospective chart review (n = 123) including 13 patients 2 to 5 years, 7 of which were hypertensive. Mean maximum dose in this age group was 0.17 +/- 0.2 mg/kg/day; this was similar to the mean dose in the older age groups.
Infants and Children younger than 2 years*: Limited data available. 0.07 to 0.1 mg/kg/dose PO once daily, initially. May increase dose if further control is needed. Max: 0.6 mg/kg/day. An initial dose of 0.1 mg/kg PO once daily, adjusted according to clinical response (Max: 0.5 mg/kg/day) was reported in a retrospective chart review (n = 123) including 13 patients 2 to 23 months, 9 of which were hypertensive. Mean maximum dose in this age group was 0.33 +/- 0.39 mg/kg/day; this was higher in comparison to the older age groups.
For the treatment of heart failure:
Oral dosage:
Adults: 2.5 to 5 mg PO once daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 20 to 40 mg/day. Guidelines recommend an angiotensin-converting enzyme (ACE) inhibitor to reduce morbidity and mortality in persons with chronic reduced ejection fraction heart failure (HFrEF) when the use of an angiotensin receptor neprilysin inhibitor (ARNI) is not feasible. ACE inhibitors are not recommended as an alternative to an ARNI in persons with preserved ejection fraction heart failure (HFpEF) due to lack of demonstrated benefit.
For the treatment of acute myocardial infarction for reduction of cardiovascular mortality:
Oral dosage:
Adults who are hemodynamically stable: 5 mg PO every 24 hours for 2 doses, then after 48 hours, 10 mg PO once daily.
Adults who have low systolic blood pressure (100 to 120 mmHg): 2.5 mg PO once daily for 3 days, then 2.5 or 5 mg PO once daily. Discontinue if prolonged hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour) occurs.
For the treatment of persistent albuminuria* in persons with diabetic nephropathy* or in at-risk hypertensive persons*:
Oral dosage:
Adults: 10 mg PO once daily, initially. Adjust dose based on blood pressure and serum creatinine and potassium concentrations every 2 to 4 weeks up to the maximum tolerated dose. Max: 40 mg/day.
To control the rate of progression of diabetic retinopathy* in patients with normotensive type I diabetes mellitus:
Oral dosage:
Adults: 10 to 20 mg/day PO has been studied. The EUCLID trial evaluated normotensive patients with type 1 diabetes mellitus. Retinal photography was performed at baseline and after 2 years of therapy with lisinopril. Over the course of the study, retinopathy worsened by one stage in only 13% of lisinopril subjects compared to 23% of placebo subjects (p = 0.02). Progression by at least 2 stages was also less in the lisinopril group.
For migraine prophylaxis*:
Oral dosage:
Adults: 2.5 or 10 mg PO once daily for 1 week, then 5 or 20 mg PO once daily. Guidelines classify lisinopril as having probable efficacy for migraine prophylaxis.
For the treatment of proteinuria* in persons with IgA nephropathy:
Oral dosage:
Adults: 10 to 20 mg PO once daily. Guidelines recommend all persons with proteinuria more than 0.5 g/day, irrespective of whether they have hypertension, be treated with an angiotensin-converting enzyme inhibitor.
Children and Adolescents 2 to 17 years: 0.1 to 0.2 mg/kg/dose (Max: 10 mg/dose) PO once daily for 1 week, then 0.4 mg/kg/dose (Max: 20 mg/dose) PO once daily. Guidelines recommend all children with proteinuria more than 200 mg/day or protein-creatinine ratio more than 200 mg/g (more than 0.2 g/g [20 mg/mmol]) receive an angiotensin-converting enzyme inhibitor.
Therapeutic Drug Monitoring:
Patients with Hyponatremia Dosing
-Serum sodium less than 130 mEq/L: The recommended initial dose for heart failure is 2.5 mg PO once daily.
Maximum Dosage Limits:
-Adults
80 mg/day PO for hypertension; 40 mg/day PO for heart failure.
-Geriatric
80 mg/day PO for hypertension; 40 mg/day PO for heart failure.
-Adolescents
0.6 mg/kg/day (Max: 40 mg/day) PO.
-Children
6 to 12 years: 0.6 mg/kg/day (Max: 40 mg/day) PO.
1 to 5 years: Safety and efficacy have not been established; however, doses up to 0.6 mg/kg/day PO have been used off-label.
-Infants
Safety and efficacy have not been established; however, doses up to 0.6 mg/kg/day PO have been used off-label.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Adult patients
CrCl more than 30 mL/minute: No dosage adjustment needed.
CrCl 10 to 30 mL/minute: Reduce initial recommended dose by 50% for adults (i.e., 5 mg PO once daily for hypertension, 2.5 mg PO once daily for heart failure and acute myocardial infarction). Max: 40 mg/day.
CrCl less than 10 mL/minute: Reduce initial dosage to 2.5 mg PO once daily. Max: 40 mg/day.
Pediatric patients (6 years and older)
FDA-approved labeling does not recommend use in pediatric patients with a GFR less than 30 mL/minute/1.73 m2. Alternatively, the following adjustments have been recommended:
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 50 mL/minute/1.73 m2: Administer 50% of the usual dose.
GFR less than 10 mL/minute/1.73 m2: Administer 25% of the usual dose.
Intermittent hemodialysis
Lisinopril is removed by hemodialysis. For adult patients receiving dialysis, the initial recommended dosage is 2.5 mg PO once daily. Max: 40 mg/day. In pediatric patients, administer 25% of the usual dose after dialysis.
Peritoneal dialysis
In pediatric patients, administer 25% of the usual dose after dialysis.
Continuous renal replacement therapy (CRRT)
In pediatric patients, administer 50% of the usual dose (assuming a dialysis dose of 2,000 mL/minute/1.73 m2).
*non-FDA-approved indication
Acarbose: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Acetaminophen; Aspirin: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Acetaminophen; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
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.
Aliskiren: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin-converting enzyme inhibitors (ACE inhibitors) 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, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ACE inhibitors 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-converting enzyme inhibitors (ACE inhibitors) 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, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ACE inhibitors 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. (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.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin-converting enzyme inhibitors (ACE inhibitors), 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.
Amifostine: (Major) Patients receiving angiotensin-converting enzyme inhibitors 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.
Amiloride: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor. (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.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Amlodipine; Celecoxib: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Amlodipine; Olmesartan: (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; Valsartan: (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; Valsartan; 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.
Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Angiotensin II receptor antagonists: (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.
Angiotensin II: (Moderate) Angiotensin converting enzyme inhibitors (ACE inhibitors) may increase 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. ACE inhibitors reduce the breakdown of angiotensin II.
Apomorphine: (Moderate) Use of angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as ACE inhibitors, as the risk of renal impairment may be increased.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Articaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral 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) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Dipyridamole: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Omeprazole: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Aspirin, ASA; Oxycodone: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Atenolol; Chlorthalidone: (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.
Auranofin: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Azathioprine: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Azilsartan: (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.
Azilsartan; Chlorthalidone: (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.
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.
Benazepril; 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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bismuth Subsalicylate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Bisoprolol; 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.
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-converting enzyme inhibitors. 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.
Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Bumetanide: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Bupivacaine; Meloxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including angiotensin-converting enzyme inhibitors. 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.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin-converting enzyme inhibitors, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan: (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.
Candesartan; 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.
Captopril; 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.
Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
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-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Celecoxib; Tramadol: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorothiazide: (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.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Chlorthalidone: (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.
Choline Salicylate; Magnesium Salicylate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Clozapine: (Moderate) Lisinopril may decrease the renal elimination of clozapine and metabolites. Clozapine toxicity, including irritability, anger, insomnia, nightmares and sialorrhea may occur. The mechanism of this interaction is unclear; however, as lisinopril does not undergo metabolism, cytochrome P450 enzyme involvement is unlikely. It is speculated that a decrease in renal elimination of clozapine occurs due to a lisinopril-induced reduction in glomerular filtration rate (GFR). Plasma clozapine concentrations should be measured carefully during concomitant lisinopril therapy; another antihypertensive class may need to be selected. In addition, clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Codeine; Phenylephrine; Promethazine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
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.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with angiotensin-converting enzyme inhibitors (ACE inhibitors) is necessary as there is an increased risk of hematologic toxicity (specifically leukopenia) and immunosuppression.
Cyclosporine: (Moderate) Several cases of acute renal failure have been associated with the addition of angiotensin-converting enzyme (ACE) inhibitors to cyclosporine therapy in renal transplant patients. In response to cyclosporine-induced renal afferent vasoconstriction and glomerular hypoperfusion, angiotensin II is required to maintain an adequate glomerular filtration rate. Inhibition of ACE could reduce renal function acutely. 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 ACE inhibitors or potassium salts.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Dexmethylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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 other antihypertensive agents.
Diclofenac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Diclofenac; Misoprostol: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of angiotensin-converting enzyme inhibitors. 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-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Digoxin: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). 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.
Diphenhydramine; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Diphenhydramine; Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of ACE inhibitors may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) is 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 ACE inhibitors may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) is 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 ACE inhibitors may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) is 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 ACE inhibitors may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) is 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 ACE inhibitors may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) is 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Duloxetine: (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.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Enalapril; 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.
Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and ACE inhibitors can affect renal function, concurrent administration with ACE inhibitors may increase the serum concentrations of entecavir and adverse events. Monitor for adverse effects when these drugs are coadministered.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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 angiotensin-converting enzyme inhibitors. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and angiotensin-converting enzyme (ACE) inhibitors. Hyperkalemia risk is increased when eplerenone is used with ACE inhibitors. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations.
Eprosartan: (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.
Eprosartan; 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.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Ethacrynic Acid: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Ethiodized Oil: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Etodolac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Everolimus: (Major) Avoid coadministration of everolimus with angiotensin-converting enzyme inhibitors (ACE inhibitors) as the risk of angioedema, with or without respiratory impairment, may be increased. In a pooled analysis of randomized, double-blind oncology clinical trials, angioedema was reported in 6.8% of patients receiving concomitant everolimus and ACE inhibitor therapy, compared to 1.3% of patients with an ACE inhibitor alone.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fenoprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and angiotensin-converting enzyme inhibitors (ACEI) 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.
Fluorescein: (Moderate) Patients on angiotensin-converting enzyme inhibitors are at an increased risk of adverse reactions when administered fluorescein injection. If fluorescein injection is deemed necessary in a patient on ACE inhibitor therapy, monitor as appropriate during and after the procedure.
Flurbiprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Fosinopril; 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.
Furosemide: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Gold: (Minor) Nitritoid reactions (facial flushing, diaphoresis, dizziness, nausea/vomiting, hypotension, tachycardia, syncope, and anaphylactic type reactions) or vasomotor reactions have been reported rarely in patients receiving injectable gold and concomitant ACE inhibitor therapy. Monitor closely for nitritoid reactions during co-therapy with gold and ACE inhibitor agents.
Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
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.
Hydrochlorothiazide, HCTZ; Moexipril: (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.
Hydrocodone; Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and angiotensin-converting enzyme inhibitors 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-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Ibuprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Ibuprofen; Famotidine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Ibuprofen; Oxycodone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Icatibant: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
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) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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. Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given an angiotensin-converting enzyme inhibitors (ACE Inhibitors) and diuretic therapy concomitantly.
Indomethacin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Iodixanol: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Iohexol: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Iomeprol: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Iopromide: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Ioversol: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Irbesartan: (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.
Irbesartan; 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.
Iron Dextran: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
Isocarboxazid: (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 angiotensin-converting enzyme inhibitors (ACE inhibitors). 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.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ketoprofen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Ketorolac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Lanthanum Carbonate: (Moderate) ACE Inhibitors should not be taken within 2 hours of dosing with lanthanum carbonate. Oral compounds known to interact with cationic antacids may similarly be bound with lanthanum carbonate and have their absorption reduced. If these agents are used concomitantly, separate the dosing intervals appropriately. Monitor the clinical condition of the patient to ensure the proper clinical response to the ACE inhibitor is obtained.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lisdexamfetamine: (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
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.
Lithium: (Moderate) Monitor serum lithium concentrations during concomitant angiotensin-converting enzyme inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Loop diuretics: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Losartan: (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.
Losartan; 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.
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) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Magnesium Salts: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin-converting enzyme inhibitors (ACE inhibitors).
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Monitor renal function during concomitant angiotensin-converting enzyme inhibitor and magnesium sulfate; potassium sulfate; sodium sulfate bowel preparation due to risk for renal injury; ensure adequate hydration.
Meclofenamate Sodium: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Mefenamic Acid: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Meglitinides: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Meloxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control. (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like angiotensin-converting enzyme inhibitors (ACE inhibitors). Close monitoring of blood pressure is advised.
Methenamine; Sodium Salicylate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Methylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Metolazone: (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.
Metoprolol; 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.
Miglitol: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nabumetone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Naproxen; Esomeprazole: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Nateglinide: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Nebivolol; Valsartan: (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.
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.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
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.
Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
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.
Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, including ACE inhibitors, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, ACE inhibitor therapy should be withheld, when possible, during radiopaque contrast agent administration.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (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.
Olmesartan: (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.
Olmesartan; Amlodipine; 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.
Olmesartan; 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.
Oxaprozin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. If these drugs are used together, closely monitor for changes in blood pressure.
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-converting enzyme inhibitors who are susceptible to hypotension.
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.
Phenelzine: (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 angiotensin-converting enzyme inhibitors (ACE inhibitors). 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.
Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Piroxicam: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Polyethylene Glycol; Electrolytes: (Moderate) Monitor renal function during concomitant angiotensin-converting enzyme inhibitor and magnesium sulfate; potassium sulfate; sodium sulfate bowel preparation due to risk for renal injury; ensure adequate hydration.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Monitor renal function during concomitant angiotensin-converting enzyme inhibitor and magnesium sulfate; potassium sulfate; sodium sulfate bowel preparation due to risk for renal injury; ensure adequate hydration.
Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) 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-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) 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-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin-converting enzyme inhibitors 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-converting enzyme inhibitors 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-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Pramlintide: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Prazosin: (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.
Pregabalin: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
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.
Promethazine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. 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.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Monitor heart rate and blood pressure.
Quinapril; 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.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
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 angiotensin-converting enzyme inhibitors (ACE inhibitors). 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-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and angiotensin-converting enzyme (ACE) inhibitor use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Repaglinide: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Risperidone: (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.
Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sacubitril; Valsartan: (Contraindicated) Sacubitril; valsartan is contraindicated with the concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) due to the increased risk of angioedema. Do not administer sacubitril; valsartan within 36 hours of switching to or from an ACE inhibitor. (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.
Salicylates: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Salsalate: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin-converting enzyme inhibitors.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor 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.
Sirolimus: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin-converting enzyme inhibitors, 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-converting enzyme inhibitors (ACE inhibitors). 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-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin-converting enzyme inhibitors (ACE inhibitors).
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sparsentan: (Major) Hold angiotensin-converting enzyme inhibitor therapy when initiating sparsentan and until a stable dose of sparsentan is achieved. Frequently monitor potassium during concomitant use due to the increased risk for hyperkalemia.
Spironolactone: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Spironolactone; 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. (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Sulfacetamide; Sulfur: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor 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-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulindac: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Sumatriptan; Naproxen: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Tacrolimus: (Moderate) Tacrolimus, in the absence of overt renal impairment, may adversely affect renal function. Care should be taken in using tacrolimus with other nephrotoxic drugs, including ACE inhibitors.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as Angiotensin-converting enzyme inhibitors (ACE inhibitors) may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan: (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.
Telmisartan; Amlodipine: (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.
Telmisartan; 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.
Temsirolimus: (Moderate) Monitor for signs and symptoms of angioedema if temsirolimus is administered concomitantly with lisinopril. Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with another ACE inhibitor.
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.
Thiazide diuretics: (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.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Tolmetin: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Tolvaptan: (Moderate) Monitor serum potassium concentrations closely if tolvaptan and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with ACE inhibitors compared to administration of these medications with placebo.
Torsemide: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
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.
Triamterene: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and triamterene are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Triamterene; 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. (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and triamterene are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Trimethoprim: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme (ACE) inhibitor 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.
Valsartan: (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.
Valsartan; 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.
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.
Ziprasidone: (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.
Lisinopril is an angiotensin converting enzyme (ACE) inhibitor. The beneficial effects of lisinopril in hypertension and heart failure primarily result from suppression of the renin-angiotensin-aldosterone system. ACE inhibition prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and negative feedback mediator for renin activity. Decreased angiotensin II leads to decreased blood pressure and increased plasma renin activity. In addition, baroreceptor reflex mechanisms are stimulated in response to the fall in blood pressure. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent vasodilator, to inactive peptides. Increased concentrations of bradykinin may play a secondary role in the therapeutic effects of ACE inhibitors. A bradykinin mechanism may also contribute to ACE-inhibitor-induced angioneurotic edema.
ACE-inhibitors lower blood pressure primarily by reducing vascular resistance, and have little effect on cardiac output or blood volume in otherwise healthy individuals. ACE inhibitors decrease both arterial and venous pressure, and therefore reduce both cardiac afterload and preload. ACE inhibitors also inhibit angiotensin-mediated release of norepinephrine from sympathetic nerves, decreasing vascular sensitivity to vasopressor activity; however, this action may not be clinically evident at usual doses. Decreases in plasma angiotensin II concentrations also result in a reduction in aldosterone secretion, with a subsequent decrease in sodium and water retention and a slight increase in serum potassium. As antihypertensives, ACE inhibitors reduce left ventricular hypertrophy and do not worsen insulin resistance or hyperlipidemia.
In patients with heart failure, ACE inhibitors reduce afterload, preload, and systolic wall stress so that cardiac output increases without an increase in heart rate. Additionally, ACE inhibitors promote salt excretion by augmenting renal blood flow and reducing angiotensin-mediated production of aldosterone and antidiuretic hormone. Inhibition of angiotensin also slows or reverses cardiac remodeling, increasing survival in adult patients with heart failure.
The mechanism by which lisinopril improves the outcome following an acute MI involves reduced peripheral vascular resistance, improved perfusion and a direct action on the myocardium. Addition of an ACE inhibitor within the initial 24-hour period after an acute MI, attenuates LV dilatation, improves perfusion and reduces peripheral vascular resistance. Inhibition of angiotensin II production reduces the workload on the heart, and inhibits collagen production. Plasma has a lower concentration of ACE than tissue (primarily vascular endothelial cells, but also present in other organs including the heart.) It has been postulated that short-term cardiovascular effects of ACE inhibitors are due to plasma ACE, whereas their long-term effects are due to action on tissue ACE.
Lisinopril is administered orally. It does not appear to be bound to other serum proteins and has a large volume of distribution (124 L) with only minimal amounts crossing the blood-brain barrier. Lisinopril is not metabolized, and the majority of an oral dose is excreted unchanged in the urine. Because of this, the half-life depends on renal function. In adult patients with normal renal function, multiple dosing of lisinopril results in a half-life of 12 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
Lisinopril is poorly absorbed from the GI tract after oral administration; bioavailability is approximately 25% with large interpatient variability (6% to 60%). Onset of antihypertensive activity occurs 1 hour after oral administration and persists for 24 hours. Peak reduction in blood pressure is achieved by 6 hours, which coincides with a Tmax of approximately 7 hours in adult patients. The oral solution and tablets are bioequivalent under fasted and fed conditions. Food does not alter bioavailability.
-Special Populations
Renal Impairment
Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease is clinically important only when the glomerular filtration rate (GFR) is less than 30 mL/minute. Above this GFR, the elimination half-life is little changed. However, with greater impairment, Cmax and Cmin increase, Tmax increases, and time to steady state is prolonged. Lisinopril is removed by hemodialysis.
Pediatrics
Infants, Children, and Adolescents
After doses of 0.1 to 0.2 mg/kg/day, bioavailability was approximately 28% and steady state Tmax occurred within 6 hours in a pharmacokinetic study of 29 hypertensive patients (age range: 6 to 16 years) with a glomerular filtration rate (GFR) more than 30 mL/minute/1.73 m2. In another study (n = 46; age range: 6 months to 15 years), bioavailability ranged from 20% to 36% and Tmax occurred within 5 to 6 hours. Patients 6 months to 5 years received lisinopril 0.15 mg/kg/dose once daily and those 6 to 15 years received 2.5 mg, 5 mg, or 10 mg once daily depending on their weight (less than 25 kg, 25 to 44 kg, or 45 kg or more, respectively). These values are similar to those obtained in adults. During the latter trial, Cmax and AUC were 22 ng/mL and 301 to 311 ng/mL x hour, respectively, in the patients 6 months to 5 years (n = 17) and 44 ng/mL and 550 to 570 ng/mL x hour, respectively, in patients 6 to 15 years (n = 29). The typical value of lisinopril oral clearance (systemic clearance/absolute bioavailability) in a child weighing 30 kg is 10 L/hour, which increases proportionately to renal function.
Other
Congestive Heart Failure
The bioavailability of lisinopril is reduced to 16% in adult patients with stable NYHA Class II-IV congestive heart failure, and Vd appears to be slightly smaller than in normal subjects.
Stable Kidney Transplant
In a pharmacokinetic study of daily lisinopril in 22 hypertensive pediatric patients with stable kidney transplant (age range: 7 to 17 years) and an estimated glomerular filtration rate (GFR) more than 30 mL/minute/1.73 m2, exposures (dose normalized to 0.1 mg/kg/day) were slightly lower but in the range reported in children without a kidney transplant. The lower exposure may be due in part to reduced oral bioavailability (19%), which may be related to the large number of concomitant medications kidney transplant recipients take and potential drug interactions. Tmax (5 hours) and terminal half-life (9.5 hours) were also similar between the two populations. As expected, clearance declined in proportion to underlying kidney function.