BiDil

Nitrites and Nitrates, Combination

Oral Administration

Hydrazlaine; isosorbide dinitrate May be administered without regards to meals. 
No information is available on the effects of food on the bioavailability of hydralazine and isosorbide dinitrate from BiDil tablets; the oral absorption of hydralazine is enhanced by food, which decreases the first-pass metabolism of hydralazine within the gastrointestinal wall.

Severe

ventricular tachycardia / Early / 4.0-4.0
myocardial infarction / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
methemoglobinemia / Early / Incidence not known
cyanosis / Early / Incidence not known
ileus / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known

Moderate

hypotension / Rapid / 8.0-8.0
amblyopia / Delayed / 3.0-3.0
impotence (erectile dysfunction) / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
angina / Early / Incidence not known
palpitations / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
dysuria / Early / Incidence not known
impaired cognition / Early / Incidence not known
migraine / Early / Incidence not known
neuritis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
blurred vision / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
erythema / Early / Incidence not known
splenomegaly / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hepatitis / Delayed / Incidence not known

Mild

headache / Early / 50.0-50.0
dizziness / Early / 32.0-32.0
asthenia / Delayed / 14.0-14.0
nausea / Early / 10.0-10.0
paresthesias / Delayed / 4.0-4.0
vomiting / Early / 4.0-4.0
sinusitis / Delayed / 4.0-4.0
syncope / Early / Incidence not known
weight gain / Delayed / Incidence not known
weakness / Early / Incidence not known
flushing / Rapid / Incidence not known
hypoesthesia / Delayed / Incidence not known
vertigo / Early / Incidence not known
tinnitus / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
abdominal pain / Early / Incidence not known
lacrimation / Early / Incidence not known
pruritus / Rapid / Incidence not known
hyperhidrosis / Delayed / Incidence not known
purpura / Delayed / Incidence not known
myalgia / Early / Incidence not known

BiDil

Rx

Oral fixed dose combination of a peripheral vasodilator (hydralazine) and a nitrate (isosorbide dinitrate); used as adjunctive therapy for heart failure in patients self-identified as black.

For the adjunctive treatment of heart failure in patients self-identified as black taking standard heart failure therapy. Oral dosage (tablets containing 37.5 mg hydralazine and 20 mg isosorbide dinitrate) Adults

Initially, 1 tablet PO 3 times daily. Titrate dose as tolerated every 3 to 5 days up to the maximum dose of 2 tablets PO 3 times daily. Some patients may experience side effects and may need a longer period of time to reach the maximum tolerated dose. The dosage may be decreased to one-half tablet PO 3 times daily if intolerable side effects occur. Increase the dose upward again when side effects subside. Guidelines recommend hydralazine and isosorbide dinitrate in combination with angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI) for black patients with reduced ejection fraction heart failure (HFrEF) NYHA class III or IV to reduce morbidity and mortality. The combination of isosorbide dinitrate and hydralazine with an ARNI has not been robustly tested; blood pressure response should be carefully monitored.

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; however isosorbide dinitrate concentrations increase in patients with cirrhosis.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears no dosage adjustments are needed.

Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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; Dichloralphenazone; Isometheptene: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Acetazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Aldesleukin, IL-2: (Moderate) Vasodilators may potentiate the hypotension seen with aldesleukin, IL 2.
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.
Alfuzosin: (Moderate) The manufacturer of alfuzosin warns that concurrent use with nitrates has the potential to cause hypotension, orthostatic hypotension, or syncope. Caution is advisable when coadministering alfuzosin and a nitrate to patients with symptomatic hypotension or those who have had a previous hypotensive response to either agent.
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.
Alpha-blockers: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Angiotensin II receptor antagonists: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Apomorphine: (Major) Coadministration of apomorphine and nitrates can cause large decreases in blood pressure. The effect is especially of concern with use of sublingual nitroglycerin products. Instruct patients to lie down before taking a sublingual nitroglycerin dose and to remain supine for at least 45 minutes after to reduce orthostatic risk. In one evaluation, the largest mean decreases in standing systolic and diastolic blood pressure during use of apomorphine and sublingual nitroglycerin were 14.3 mmHg and 13.5 mmHg, respectively. The largest recorded decreases in standing systolic and diastolic blood pressures were 65 mmHg and 43 mmHg during use of apomorphine and sublingual nitroglycerin together. (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) Coadministration of articaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Benzalkonium Chloride; Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine; Butamben; Tetracaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Beta-adrenergic blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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 Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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. (Moderate) Cabergoline should be used cautiously with drugs that can lower blood pressure, including systemic nitrates. 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-channel blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
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.
Carbonic anhydrase inhibitors: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
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.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Coadministration of chloroprocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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; Dihydrocodeine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Dapsone: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Diethylstilbestrol, DES: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
Dihydroergotamine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Eplerenone: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Epoprostenol: (Major) Further reductions in blood pressure may occur when vasodilators are combined with epoprostenol. (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Ergoloid Mesylates: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergot alkaloids: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergotamine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergotamine; Caffeine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
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.
Fenoldopam: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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 f

or 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) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lisdexamfetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Mannitol: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Mecamylamine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metformin; Rosiglitazone: (Major) The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
Methamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Methazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
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.
Methylergonovine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Methylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Minoxidil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates. (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.
Niacin; Simvastatin: (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.
Nitroprusside: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Norepinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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 and enhance the orthostatic effects of nitrates. Orthostatic vital signs should be monitored in patients receiving paliperidone and nitrates who are susceptible to hypotension. (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and hydralazine who are susceptible to hypotension.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Phosphodiesterase inhibitors: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
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: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Riociguat: (Contraindicated) Coadministration of riociguat and nitrates or nitric oxide donors (e.g., amyl nitrite) is contraindicated due to the risk of hypotension. The blood pressure lowering effect of sublingual nitroglycerin was potentiated when administered 4 and 8 hours after riociguat. Syncope was reported in some patients.
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.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rosiglitazone: (Major) The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
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) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent nitrates. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Sympathomimetics: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (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 or rapid-onset vasodilators, such as nitrates. (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: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
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.
Treprostinil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Vincristine Liposomal: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
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.

BiDil/Isosorbide Dinitrate, Hydralazine Hydrochloride Oral Tab: 20-37.5mg

Adults

225 mg/day PO hydralazine and 120 mg/day PO isosorbide dinitrate.

Elderly

225 mg/day PO hydralazine and 120 mg/day PO isosorbide dinitrate.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

The mechanism of action underlying the beneficial effects of hydralazine; isosorbide dinitrate in the treatment of heart failure has not been established. Analysis of previous trials has illustrated the clinical benefit of hydralazine; isosorbide dinitrate as adjunctive therapy to a stable drug regimen for heart failure, especially in the African-American population. It is postulated that vasoreactivity may be impaired in black patients. Furthermore, evidence shows that this ethnic group responds differently than non-black patients to conventional heart failure therapy (e.g., ACE inhibitors). It is theorized that black patients may have lower concentrations of nitric oxide within the coronary and peripheral vasculature. This insufficiency is proposed to be attributable to a reduction of nitric oxide (NO) production, enhanced NO inactivation, or possibly both. Additionally, the vascular response to NO is markedly reduced in black subjects.
 
The combined efficacy of hydralazine plus isosorbide dinitrate has been established by the Vasodilator-Heart Failure Trails (V-HeFT) in the overall population of those studies. This combination has been used in patients with symptomatic heart failure with or without the concomitant use of an ACE inhibitor. The recent re-analysis of the V-HeFT I and II trials has found that hydralazine plus isosorbide dinitrate reduces mortality at a greater significance in black patients when compared to white patients. V-HeFT I reported a statistically significant improvement in exercise tolerance in black patients receiving the hydralazine; isosorbide dinitrate combination versus placebo. V-HeFT II demonstrated improved quality of life in black patients receiving combined hydralazine; isosorbide dinitrate therapy compared to enalapril. Subsequently, the African-American Heart Failure Trial (A-HeFT) evaluated a fixed-dose combination of hydralazine and isosorbide dinitrate to treat African-American patients receiving standard therapy for heart failure (primarily NYHA Class III). The combination therapy, when compared to placebo, reduces the rate of death by 43%, reduces the rate of first hospitalization by 33%, and improves patient-reported functional status. In the A-HeFT trial, patients receiving hydralazine; isosorbide dinitrate also received concurrent therapy with ACE inhibitors (69%), angiotensin II receptor blockers (17%), beta-blockers (74%), diuretics (88%), cardiac glycosides (59%), and/or diuretics (88%).
 
•Hydralazine: Hydralazine is a selective dilator of arterial smooth muscle. 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 unclear, but it may be similar to organic nitrates and sodium nitroprusside. In contrast to these agents, however, hydralazine is selective for the arterioles. In addition, animal and limited human data indicate that 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.
 
There is also evidence suggesting hydralazine exerts a positive inotropic effect on the failing human ventricle. Cerebral, coronary, splanchnic, and renal blood flow usually increase following administration of hydralazine, while urinary parameters are generally unaffected. 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.
 
•Isosorbide dinitrate: Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), a reactive free radical. Nitric oxide is also formed endogenously and is believed to be endothelial-derived growth factor. Among other properties, NO is believed to produce vasodilation. Nitric oxide, the active intermediate compound common to all agents of this class, activates the enzyme guanylate cyclase, thereby stimulating the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP). This second messenger then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber and the subsequent release, or extrusion, of calcium ions. The contractile state of smooth muscle is normally maintained by a phosphorylated myosin light chain (stimulated by an increase in calcium ions). Thus, the nitrite- or nitrate-induced dephosphorylation of the myosin light chain signals the cell to release calcium, thereby relaxing the smooth muscle cells and producing vasodilation.
 
It is believed that nitrates correct myocardial oxygen imbalances by reducing systemic and pulmonary arterial pressure (afterload) and decreasing cardiac output secondary to peripheral dilation rather than coronary artery dilation. Nitrates therefore relax peripheral venous vessels, causing a pooling of venous blood and decreased venous return to the heart, which decreases preload. Nitrates reduce both arterial impedance and venous filling pressures, resulting in a reduction of the left ventricular systolic wall tension, thereby decreasing afterload
 
Nitrates cause a transient reflex compensatory increase in heart rate and myocardial contractility that would normally increase myocardial oxygen consumption, yet the nitrate-induced decrease in ventricular wall tension results in a net decrease in myocardial oxygen demand and amelioration of the pain of angina pectoris. In addition, isosorbide relaxes all other types of smooth muscle including bronchial, biliary, GI, ureteral, and uterine. Nitrites and nitrates are functional antagonists of acetylcholine, norepinephrine, and histamine.

Hydralazine; isosorbide dinitrate is administered orally. When given in combination, the half-life is 4 and 2 hours for the hydralazine and isosorbide dinitrate components, respectively.
Hydralazine: 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. 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—7 hours.
Isosorbide Dinitrate: Isosorbide dinitrate distributes throughout the body tissues and is metabolized by denitration to isosorbide-2-mononitrate or isosorbide-5-mononitrate, both of which are pharmacologically active and can contribute to the efficacy of isosorbide dinitrate. ISDN is virtually completely metabolized, with minute portions of the parent drug and metabolites excreted renally.

Oral Route

Following oral administration of hydralazine; isosorbide dinitrate, peak plasma concentrations are reached in 1 hour. No information is available in regards to the effects of food on the bioavailability of hydralazine and isosorbide dinitrate from BiDil tablets.
Hydralazine: Hydralazine is rapidly absorbed via the gastrointestinal tract with approximately 90% of the dose absorbed following oral administration. Oral bioavailability is affected by extensive first-pass metabolism and is dependent on the acetylation phenotype of the patient; 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. Hypotensive effects occur 20—30 minutes following an oral dose. The antihypertensive effects of an oral hydralazine dose last about 2—4 hours.
Isosorbide Dinitrate: Orally administered isosorbide dinitrate is absorbed rapidly from the GI tract but undergoes extensive first-pass metabolism, resulting in a bioavailability of 22%. The onset of action of isosorbide begins in 15—40 minutes following drug administration and the duration of effect is 4—6 hours.

Pregnancy

There are no studies of hydralazine; isosorbide dinitrate in pregnant women. Available data for hydralazine; isosorbide dinitrate use in the first trimester are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Hydralazine has been administered to pregnant women with severe hypertension (including preeclampsia). When compared to other antihypertensive agents, hydralazine is associated with significantly more maternal hypotension, placental abruption, cesarian sections, oliguria, adverse effects on fetal heart rate, in addition to lower Apgar scores.  Hydralazine related teratogenic effects were seen in mice and possibly rabbits that received doses 2 to 3 times the maximum recommended human dose (MRHD) of hydralazine; isosorbide dinitrate. A dose-related increase in embryotoxicity (excess mummified pups) has been found in rabbits that received isosorbide dinitrate at doses of 12 times the MRHD of hydralazine; isosorbide dinitrate. Heart failure is associated with an increased risk of preterm birth and worsening of heart disease during pregnancy may lead to maternal death and stillbirth.

There are no data on the presence of hydralazine; isosorbide in human milk, the effects on the breast-fed infant, or the effects on milk production. [31394] The molecular weight of isosorbide dinitrate is low enough that excretion of the drug into breast milk should be expected.[48695] Hydralazine is excreted into breast milk, but the exposure to a nursing infant is not expected to be clinically significant.[48682] Previous American Academy of Pediatrics recommendations did not evaluate the use of isosorbide dinitrate in breast-feeding but considered hydralazine to be compatible with breast-feeding.[27500] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.