Hydralazine is an oral and parenteral antihypertensive agent. Because it is a peripheral vasodilator, hydralazine also has been used to treat congestive heart failure, although ACE inhibitors have largely replaced hydralazine for this use. In those patients that cannot tolerate ACE inhibitors or angiotensin II blockers, hydralazine in combination with isosorbide dinitrate is an acceptable alternative for the treatment of heart failure. Hydralazine was one of the earliest orally active antihypertensive agents and has been commonly used for hypertension during pregnancy. Hydralazine also has been used to treat pulmonary hypertension, but the actions are unpredictable, causing either improved hemodynamic status or symptomatic hypotension. More recently, hydralazine's use in the general population has declined due to adverse effects, tachyphylaxis, and the release of newer and better-tolerated agents. In addition, injectable hydralazine has historically been used as a first-line agent in the treatment of hypertensive emergencies and urgencies including preeclampsia; however, due to unpredictable falls in blood pressure, a prolonged duration of action (up to 12 hours or more), and adverse effects, its use as a first-line agent for these indications is being replaced by newer and more predictable injectable antihypertensives.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer consistently with regards to timing around meals/food to ensure consistent oral absorption of hydralazine.
Injectable Administration
-Hydralazine can be administered intramuscularly or as a rapid IV injection. Do not add hydralazine to any IV solutions.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Administer dose immediately after opening the vial.
-Hydralazine changes color after contact with metal, discard any discolored hydralazine solution.
-Blood pressure should be checked frequently following administration of injectable hydralazine.
Intravenous Administration
-Inject undiluted injection IV via Y-site or a 3-way stopcock at a rate of 10 mg over at least 1 minute.
Intramuscular Administration
-No dilution necessary.
-Inject deeply into a large muscle.
The most common adverse effects of hydralazine administration are headache, angina pectoris, palpitations, sinus tachycardia, anorexia, nausea, vomiting, and diarrhea. Initiation of therapy with low doses and a gradual increase until a satisfactory antihypertensive effect is obtained will help to minimize adverse reactions. As hydralazine may be used for treatment of hypertension associated with severe pre-eclampsia, it should be noted that adverse effects associated with hydralazine, such as headache, nausea, and vomiting, can mimic deteriorating pre-eclampsia.
Hydralazine is a potent vasodilator and can result in hypotension including orthostatic hypotension, dizziness, syncope, reflex tachycardia, peripheral vasodilation, peripheral edema, and fluid retention. Hydralazine-induced fluid retention can cause edema and weight gain. These effects usually can be alleviated by concomitant administration of a thiazide diuretic. Myocardial infarction has also been reported.
Gastrointestinal adverse effects that occur infrequently with hydralazine are constipation and paralytic ileus.
Hypersensitivity and lupus-like symptoms, manifested by fever, chills, sore throat, myalgia, arthralgia, glomerulonephritis, pericarditis, pleuritis, cutaneous vasculitis (skin blisters), rash (unspecified), pruritus, urticaria, eosinophilia, and erythema can occur with hydralazine. Hepatitis has been reported rarely with hydralazine. Hydralazine is the most frequent drug implicated in producing lupus-like symptoms. Hydralazine is metabolized by acetylation. The patient's acetylation phenotype will affect the plasma concentration of hydralazine. Patients who are 'slow acetylators' as well as patients with decreased renal function are more likely than fast acetylators to develop lupus-like symptoms. Patients with decreased renal function, patients receiving more than 200 mg/day, and patients with a family history of autoimmune disease, are also more likely to develop this condition. Although some manifestations are similar, drug-induced lupus occurs via a different mechanism than idiopathic disease. Patients should be instructed to report adverse symptoms of joint pain, muscle pain, angina, fever or continued weakness to their physician. If hydralazine-induced lupus syndrome is suspected, the drug should be discontinued.
Hydralazine can cause peripheral neuropathy, evidenced by paresthesias (numbness, pain, and tingling in the hands and feet). Significant increases in urinary xanthurenic acid may indicate pyridoxine deficiency; therefore, an antipyridoxine mechanism has been suggested. If symptoms do develop, the addition of pyridoxine to the regimen is suggested.
Blood dyscrasias such as agranulocytosis, leukopenia, anemia (defined as reduction of hemoglobin and red cell count), and purpura have been reported during hydralazine therapy. Complete blood counts should be undertaken before therapy with hydralazine and periodically thereafter, especially during prolonged therapy. Hydralazine therapy should be discontinued if there is evidence of blood dyscrasias.
There have been occasional reports of dyspnea, lacrimation, conjunctivitis, flushing, muscle cramps, tremor, lymphadenopathy, splenomegaly, and nasal congestion with hydralazine therapy.
Depression, anxiety, and disorientation (confusion) have been reported as less frequent adverse reactions with hydralazine therapy.
Hydralazine may produce a clinical picture simulating systemic lupus erythematosus (SLE) including glomerulonephritis. Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine. Hydralazine is subject to polymorphic acetylation; slow acetylation status results in higher plasma levels of hydralazine and these patients require lower doses to maintain control of blood pressure. Thus, the patient's acetylation phenotype will affect the plasma concentration of hydralazine. Patients who are slow acetylators as well as patients with decreased renal function are more likely than fast acetylators to develop lupus-like symptoms or potentially other hydralazine toxicity. Patients with decreased renal function, patients receiving more than 200 mg/day, and patients with a family history of autoimmune disease are also more likely to develop this condition. It is difficult to provide guidelines regarding administration of hydralazine to patients with preexisting systemic lupus erythematosus (SLE). Although hydralazine has been administered safely to these patients, with no exacerbation of underlying disease, and the mechanism of hydralazine-induced lupus syndrome appears to be distinct from idiopathic lupus, hydralazine should nevertheless be used cautiously in this population. Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy, even if the patient does not have any symptoms; these tests are also indicated if a patients develops arthralgia, fever, chest pain, continued malaise, or other unexplained symptoms. If hydralazine-induced SLE occurs, the drug should be discontinued, unless the benefit of continued antihypertensive therapy with this drug outweighs the risk. Signs and symptoms of lupus usually regress when the drug is discontinued; however, residual signs and symptoms have been detected many years later. Long-term treatment with systemic steroids may be necessary.
Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine. In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate (GFR). In some instances where control values were below normal, improved renal function has been noted after administration of the drug. However, as with any antihypertensive agent, hydralazine should be used with caution in patients with advanced renal damage. Some references state to consider extended dose intervals in patients with renal impairment (CrCl 10 to 50 mL/min). Patients with renal impairment should receive the drug every 8 hours. Patients with renal failure (CrCl less than 10 mL/min) should receive the drug every 8 to 16 hours; based on patient response, intervals of 12 to 24 hours may be needed.
Hydralazine is contraindicated in patients with mitral valve rheumatic heart disease because it can increase pulmonary artery pressure. Additionally, it has been implicated in causing angina and myocardial infarction secondary to reflex sympathetic nervous system stimulation (i.e., reflex tachycardia); therefore, hydralazine is contraindicated in patients with coronary artery disease as reflex tachycardia increases myocardial oxygen demand, which may aggravate angina and ischemia and precipitate acute myocardial infarction. Because hydralazine can cause sodium and fluid retention, its use is generally not recommended in patients with heart failure, although it has been used in patients with intractable left ventricular dysfunction. Guidelines recommend hydralazine in combination with isosorbide dinitrate to improve symptoms and reduce morbidity and mortality in self-identified African American patients with NYHA class III or IV heart failure with reduced ejection fraction (HFrEF) receiving optimal medication therapy (i.e., angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], beta-blockers, and mineralocorticoid receptor antagonist [MRA]). Combination therapy of isosorbide dinitrate and hydralazine, in conjunction with standard therapy, has been shown to improve mortality, rate of first hospitalizations, and quality of life in black patients. Hydralazine in combination with isosorbide dinitrate may also be considered in individuals with HFrEF who are unable to receive an angiotensin receptor-neprilysin inhibitor (ARNi), ACE inhibitor, or ARB due to intolerance or renal impairment. Use of hydralazine without a nitrate for the treatment of hypertension in patients with heart failure is not recommended.
Use hydralazine cautiously in patients with acute stroke or cerebral vascular accident as hydralazine in this setting can further worsen brain function. When hydralazine is used in the presence of increased intracranial pressure, lowering of the blood pressure may result in increased cerebral ischemia.
There are no adequate and well-controlled studies in pregnant women. Although clinical experience does not identify evidence of fetal adverse effects, use hydralazine during pregnancy only if the expected benefit outweighs the potential risk to the fetus. Intravenous hydralazine is commonly used for acute-onset severe hypertension in pregnancy. Animal studies indicate that hydralazine is teratogenic in mice at 20 to 30 times the maximum daily dose of 200 to 300 mg and possibly in rabbits at 10 to 15 times the maximum daily human dose, but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and cranial bones.
Use caution when administering hydralazine to a breast-feeding woman. Previous American Academy of Pediatrics (AAP) recommendations considered hydralazine to be generally compatible with breast-feeding. Hydralazine is distributed into human milk. In a case report of a mother taking hydralazine 50 mg PO 3 times daily, hydralazine breast milk concentrations were 130 mcg/L at 0.5 and 2 hours after a dose. Based on these concentrations, it is estimated that a nursing infant would receive 13 mcg of hydralazine per 75 mL of breast milk.
Hydralazine can induce disorientation or confusion. Patients should use caution when driving or operating machinery until they are aware of the effects of the medication.
Clinical experience has not identified differences in responses to hydralazine between geriatric and younger adults. Hydralazine may be eliminated more slowly in geriatric patients. When dosing hydralazine in the older adult, it may be prudent to start the dose at the low end of the dosing range and monitor the patient closely for hypotensive effects. Subsequent dosage adjustments should be made based on clinical response.
For the treatment of hypertension:
Oral dosage:
Adults: 10 mg PO 4 times daily for 2 to 4 days, then 25 mg PO 4 times daily for the balance of the first week, initially. May increase dose to 50 mg PO 4 times daily if further control is needed. Usual dose range: 100 to 200 mg/day in 2 to 4 doses. Max: 300 mg/day.
Infants*, Children*, and Adolescents*: 0.75 mg/kg/day PO in 4 divided doses (Max: 25 mg/dose), initially. May increase dose over 3 to 4 weeks if further control is needed. Max: 7.5 mg/kg/day or 200 mg/day, whichever is less.
Neonates*: Limited data available. 0.25 to 1 mg/kg/dose PO 3 to 4 times daily has been suggested. May gradually increase dose if further control is needed. Max: 7.5 mg/kg/day.
Intravenous Route:
Adults: 10 to 20 mg IV every 4 to 6 hours as needed. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Infants*, Children*, and Adolescents*: 0.2 to 0.6 mg/kg/dose (Max: 20 mg/dose) IV every 4 hours as needed. Max: 1.7 to 3.5 mg/kg/day. Use IV route only if PO is not feasible. Switch to oral therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Neonates*: Limited data available. 0.15 to 0.6 mg/kg/dose IV every 4 hours as needed has been suggested. Only use IV route if PO is not feasible. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Intramuscular dosage:
Adults: 10 to 50 mg IM every 4 to 6 hours as needed. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours.
Infants*, Children*, and Adolescents*: 0.2 to 0.6 mg/kg/dose (Max: 20 mg/dose) IM every 4 hours as needed. Max: 1.7 to 3.5 mg/kg/day. Use IM route only if PO is not feasible. Switch to oral therapy as soon as possible, usually within 24 to 48 hours.
For the treatment of hypertensive emergency or hypertensive urgency:
Intravenous dosage:
Adults: 10 to 20 mg IV every 4 to 6 hours as needed. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Infants*, Children*, and Adolescents*: 0.1 to 0.2 mg/kg/dose (Max: 20 mg/dose) IV every 4 to 6 hours as needed; may increase the dose slowly up to 0.6 mg/kg/dose (Max: 20 mg/dose). Switch to oral therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Neonates*: Limited data. A dose of 0.15 to 0.6 mg/kg/dose IV administered every 4 hours as needed has been suggested. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.
Intramuscular dosage:
Adults: 10 to 50 mg IM every 4 to 6 hours as needed. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours.
Infants*, Children*, and Adolescents*: 0.1 to 0.2 mg/kg/dose (Max: 20 mg/dose) IM every 4 to 6 hours as needed; may increase dose slowly up to 0.6 mg/kg/dose (Max: 20 mg/dose). Switch to oral therapy as soon as possible, usually within 24 to 48 hours.
Oral dosage*:
Children and Adolescents: 0.25 mg/kg/dose (Max: 25 mg/dose) PO every 6 to 8 hours as needed.
For the treatment of heart failure*:
Oral dosage:
Adults: 25 to 50 mg PO 3 to 4 times daily, initially. Increase the dose every 1 to 2 weeks to the highest dosage level tolerated. Max: 300 mg/day. Guidelines recommend hydralazine plus isosorbide dinitrate to improve symptoms and reduce morbidity and mortality in persons self-identified as Black with NYHA class III to IV reduced ejection fraction heart failure (HFrEF) who are receiving optimal medical therapy. In persons with HFrEF who cannot be given first-line agents, such as an angiotensin receptor neprilysin inhibitor (ARNI), angiotensin-converting enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB), because of drug intolerance or renal insufficiency, a combination of hydralazine and isosorbide dinitrate may be considered to reduce morbidity and mortality.
Infants, Children, and Adolescents: 0.25 to 1 mg/kg/dose PO every 6 to 8 hours, initially. Increase the dose as needed. Max: 7 mg/kg/day. The incidence of systemic lupus erythematosus is higher in patients receiving doses more than 200 mg/day.
Intravenous dosage:
Infants, Children, and Adolescents: 0.1 to 0.5 mg/kg/dose IV every 6 to 8 hours. Switch to oral therapy as soon as possible.
For the treatment of hypertension associated with preeclampsia* or eclampsia*:
Intravenous dosage:
Adults: 5 mg IV, then 5 to 10 mg IV every 20 to 40 minutes until goal blood pressure is attained. Max cumulative dose: 20 mg.
Adolescents: 5 mg IV, then 5 to 10 mg IV every 20 to 40 minutes until goal blood pressure is attained. Max cumulative dose: 20 mg.
Continuous Intravenous Infusion dosage:
Adults: 0.5 to 5 mg/hour continuous IV infusion, initially. Titrate by 1 to 2 mg/hour every 15 to 20 minutes until goal blood pressure is attained. Max: 10 mg/hour.
Adolescents: 0.5 to 5 mg/hour continuous IV infusion, initially. Titrate by 1 to 2 mg/hour every 15 to 20 minutes until goal blood pressure is attained. Max: 10 mg/hour.
Maximum Dosage Limits:
-Adults
300 mg/day PO for hypertension. Higher doses have been used to treat patients with heart failure; however, doses greater than 200 to 300 mg/day PO are associated with a higher risk of drug-induced systemic lupus erythematosus. Titrate IV and IM dosage as needed for blood pressure control.
-Geriatric
300 mg/day PO for hypertension. Higher doses have been used to treat patients with heart failure; however, doses greater than 200 to 300 mg/day PO are associated with a higher risk of drug-induced systemic lupus erythematosus. Titrate IV and IM dosage as needed for blood pressure control.
-Adolescents
Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 200 mg/day PO, whichever is less, or 3.5 mg/kg/day IV or IM have been used.
-Children
Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 200 mg/day PO, whichever is less, or 3.5 mg/kg/day IV or IM have been used.
-Infants
Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 3.5 mg/kg/day IV or IM have been used.
-Neonates
Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 0.6 mg/kg/dose IV have been used.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available. Hydralazine is extensively metabolized in the liver and is subject to polymorphic acetylation; patients with slow acetylation status have higher plasma levels of hydralazine and these patients require lower doses to maintain control of blood pressure.
Patients with Renal Impairment Dosing
CrCl more than 50 mL/minute: no dosage adjustment needed.
CrCl 10 to 50 mL/minute: administer every 8 hours.
CrCl less than 10 mL/minute: administer every 8 to 16 hours. Interval may be extended to 12 to 24 hours based on patient response.
Intermittent hemodialysis
Administer every 12 to 24 hours depending on patient blood pressure.
Peritoneal dialysis
Administer every 12 to 24 hours depending on patient blood pressure.
*non-FDA-approved indication
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Acrivastine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as hydralazine, however, this interaction has not been studied.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as the vasodilators, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amphetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Amphetamine; Dextroamphetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Apomorphine: (Moderate) Concurrent use of apomorphine and vasodilators can cause greater decreases in blood pressure than use of apomorphine alone. Patients receiving a combination of apomorphine and vasodilators should be closely monitored for hypotension and orthostasis.
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.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Articaine; Epinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
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.
Benzphetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension (including orthostatic hypotension) was reported in roughly 12 percent of patients; most events were mild to moderate in severity, with more dramatic hypotension reported in 4 percent of drug recipients. Additionally, bortezomib and hydralazine can both cause peripheral neuropathy; coadminister these drugs cautiously, as the risk of peripheral neuropathy may be additive.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Bupivacaine; Epinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including hydralazine. 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.
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.
Cetirizine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
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) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Codeine; Phenylephrine; Promethazine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and hydralazine use. Concomitant use may result in additive hypotension.
Conjugated Estrogens: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Conjugated Estrogens; Bazedoxifene: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Conjugated Estrogens; Medroxyprogesterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Desloratadine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Desogestrel; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and vasodilators could lead to additive hypotension and bradycardia; use together with caution. In clinical trials where vasodilators were co-administered with dexmedetomidine an additive pharmacodynamic effect was not observed. However, both vasodilators and dexmeditomidine may cause symptomatic hypotension. If hypotension occurs, dose reduction of one or both drugs may be needed and supportive measures instituted.
Dexmethylphenidate: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dextroamphetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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) Hypotension and bradycardia have been reported when diazoxide and hydralazine were administered together. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving hydralazine.
Dienogest; Estradiol valerate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Diethylpropion: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Diphenhydramine; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dobutamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Dopamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Doxapram: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Drospirenone; Estetrol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Drospirenone; Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Drospirenone; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Duloxetine: (Moderate) Monitor blood pressure during concomitant duloxetine and hydralazine use. Concomitant use increases the risk for hypotension, including orthostatic hypotension and syncope. Consider reducing the duloxetine dose or discontinuing duloxetine if symptomatic orthostatic hypotension, falls, or syncope occur during treatment.
Elagolix; Estradiol; Norethindrone acetate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Ephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Ephedrine; Guaifenesin: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Epinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Epoprostenol: (Major) Further reductions in blood pressure may occur when vasodilators are combined with epoprostenol.
Esterified Estrogens: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Esterified Estrogens; Methyltestosterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estradiol; Levonorgestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estradiol; Norethindrone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estradiol; Norgestimate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estradiol; Progesterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estrogens: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Estropipate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Ethinyl Estradiol; Norelgestromin: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Ethinyl Estradiol; Norgestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Etonogestrel; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Fexofenadine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Guaifenesin; Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Guaifenesin; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Ibritumomab Tiuxetan: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Ibuprofen; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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) Vasodilators may have additive hypotensive effects when given with other antihypertensive agents.
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.
Isocarboxazid: (Moderate) Monoamine oxidase inhibitors (MAOIs) potentiate the concentration of catecholamines in the CNS. These effects can be additive with those of hydralazine, so caution should be used when administering these drugs together. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, a serious interaction with hydralazine is expected to be less likely to occur with rasagiline.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Isoproterenol: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Levonorgestrel; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Lidocaine; Epinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Lisdexamfetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Lofexidine: (Major) Because the central alpha-2 agonist effects of lofexidine can cause hypotension and orthostasis, the drug should be avoided, if possible, in combination with other medications that can decrease blood pressure such as systemic vasodilators. If coadministration is required, blood pressure should be monitored, particularly after dose changes of either agent. Adjustments should be made as clinically indicated.
Loratadine; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
Methamphetamine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methylphenidate: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Midodrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Naproxen; Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Nesiritide, BNP: (Moderate) The potential for hypotension may be increased when coadministering nesiritide with vasodilators. Reduce the dose of or discontinue nesiritide in patients who develop hypotension. In clinical trials, no drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers, such as vasodilators.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Nitrates: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Norepinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Norethindrone; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Norgestimate; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
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.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by vasodilators. Also vasodilators can antagonize the effectiveness of oxymetazoline. 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 hydralazine 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.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with hydralazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phendimetrazine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Phenelzine: (Moderate) Monitor blood pressure during concomitant hydralazine and phenelzine use due to the risk for additive hypotension.
Phentermine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Phentermine; Topiramate: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Phenylephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
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.
Pretomanid: (Major) Avoid coadministration of pretomanid with hydralazine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine; Epinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pseudoephedrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Pseudoephedrine; Triprolidine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Racepinephrine: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Rasagiline: (Moderate) Monoamine oxidase inhibitors (MAOIs) potentiate the concentration of catecholamines in the CNS. These effects can be additive with those of hydralazine, so caution should be used when administering these drugs together. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, a serious interaction with hydralazine is expected to be less likely to occur with rasagiline.
Relugolix; Estradiol; Norethindrone acetate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and hydralazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
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.
Segesterone Acetate; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
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.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Sulfacetamide; Sulfur: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
Sympathomimetics: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
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.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
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.
Tranylcypromine: (Major) Avoid concomitant use of vasodilators and tranylcypromine due to the risk of additive hypotension. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the vasodilator). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure closely.
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.
Vincristine Liposomal: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Vitamin B Complex Supplements: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
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.
Hydralazine is a peripheral vasodilator; it causes relaxation of arteriolar smooth muscle via a direct effect. Although stimulation of the sympathetic nervous system is associated with hydralazine administration, this is a compensatory response and not a component of its mechanism. The molecular explanation of hydralazine's mechanism is not fully understood; however, similar to organic nitrates and nitroprusside, it is thought that hydralazine interferes with the calcium movements within vascular smooth muscle that are responsible for initiating and maintaining the contractile state. In contrast to organic nitrates and sodium nitroprusside, however, hydralazine is selective for arterioles. The peripheral vasodilating effects of hydralazine result in decreased arterial blood pressure (diastolic more than systolic) and peripheral vascular resistance. In addition, the hydralazine-induced reflex autonomic response increases heart rate, stroke volume, cardiac output, and left ventricular ejection fraction. The preferential dilation of arterioles, as compared to veins, minimizes postural hypotension and promotes the increase in cardiac output even though the hypotensive effects of hydralazine are diminished somewhat by this increase in cardiac output. There is also evidence suggesting hydralazine exerts a positive inotropic effect on the failing human ventricle.
Animal and limited human data indicate that nitric oxide (NO) may be generated from hydralazine that also has an antioxidant quality to enhance the effects of nitrates and to mitigate the tolerance associated with chronic nitrate therapy. The antioxidant effect of hydralazine can be attributed to its ability in inhibiting oxidase formation. The accumulation of oxidative free radicals creates an environment where chronic reductions in NO bioavailability contribute to a loss of skeletal muscle microvessels. This effect, in turn, leads to impaired muscle perfusion with elevated metabolic demand. Studies show that treatment with hydralazine markedly inhibits oxidase which plays a role in regulating the bioactivity of NO, produced either endogenously or when administered exogenously.
Cerebral, coronary, splanchnic, and renal blood flow usually increase following administration of hydralazine, while urinary parameters are generally unaffected. Hydralazine increases renin activity in plasma, presumably by the renal juxtaglomerular cells in response to sympathetic nervous system stimulation; the increase in renin activity leads to the production of angiotensin II, which stimulates aldosterone and thus, sodium reabsorption. Due to fluid retention, plasma volume increases. As a result, tolerance can develop, which may account for the absence of improvement in some patients receiving the drug for prolonged periods of time.
As an antihypertensive, hydralazine does not lead to improvements in LVH. Hydralazine may actually worsen LVH, potentially due to reflex tachycardia and sympathetic stimulation, which may counteract the benefits of afterload reduction.
Hydralazine is administered orally and parenterally. Hydralazine distributes throughout the body tissues and has a particularly high affinity for arterial walls. The drug crosses the placenta and distributes in breast milk, but not to a clinically significant degree. Plasma protein binding is about 87%. Hydralazine is extensively hepatically metabolized, and plasma levels can vary due to polymorphic acetylation. Both the unchanged drug (25%) and its metabolites are excreted in the urine and feces. The half-life of the drug in a normal patient is 3 to 7 hours.
Affected CYP450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
Although hydralazine is approximately 90% absorbed following oral administration, systemic bioavailability is considerably lower after oral versus intramuscular or intravenous administration due to extensive first-pass metabolism. Oral bioavailability is also dependent on the acetylation phenotype of the patient, and it is approximately 50% in 'slow' acetylators and 30% in 'fast' acetylators. Although food in the gut enhances absorption of hydralazine, food-related reductions in hydralazine blood levels have been associated with reduced antihypertensive effects, possibly due to an increase in intravascular conversion of the drug to hydralazine pyruvic acid hydrazone. For this reason, it has been suggested that patients take this medication at a fixed time in relationship to meals. Peak hydralazine plasma concentration is reached in 1 to 2 hours. Hypotensive effects occur 20 to 30 minutes following an oral dose. The antihypertensive effects of an oral hydralazine dose last about 2 to 4 hours.
Intravenous Route
Hypotensive effects occur 5 to 30 minutes after an IV dose. The antihypertensive effects of an IV dose last 2 to 6 hours on average, although the effects of a parenteral dose can last up to 12 hours; the affinity of hydralazine for arterial walls may partially explain the prolonged effect.
Intramuscular Route
Hypotensive effects occur 10 to 30 minutes after an IM dose. The antihypertensive effects of an IM dose last 2 to 6 hours on average, although the effects of a parenteral dose can last up to 12 hours possibly due to the affinity of hydralazine for arterial walls.
-Special Populations
Renal Impairment
The half-life of hydralazine can be prolonged in patients with renal failure.