isosorbide dinitrate/hydralazine (Rx)

Brand and Other Names:BiDil
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Dosing & Uses

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Dosage Forms & Strengths

isosorbide dinitrate/hydralazine

tablet

  • 20mg/37.5mg

Heart Failure

1 tab PO q8hr; titrate dose to effect; not to exceed 2 tab PO q8hr

Heart failure in self-identified African Americans as Adjunct Therapy

1 tab PO q8hr; titrate dose to effect; not to exceed 2 tab PO q8hr

Safety and efficacy not established

Heart failure

1 tab PO q8hr; titrate dose to effect; not to exceed 2 tab PO q8hr

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Interactions

Interaction Checker

and isosorbide dinitrate/hydralazine

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            Contraindicated (5)

            • avanafil

              isosorbide dinitrate, avanafil. Either increases effects of the other by Mechanism: additive vasodilation. Contraindicated. Contraindicated; potentially fatal hypotension.

            • riociguat

              isosorbide dinitrate, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.

            • sildenafil

              isosorbide dinitrate, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.

            • tadalafil

              isosorbide dinitrate, tadalafil. Mechanism: additive vasodilation. Contraindicated. Contraindicated. Potentially fatal hypotension. Allow 48h after last tadalafil dose before nitrate administration.

            • vardenafil

              isosorbide dinitrate, vardenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.

            Serious - Use Alternative (18)

            • abametapir

              abametapir will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • apalutamide

              apalutamide will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • cabergoline

              isosorbide dinitrate increases effects of cabergoline by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

            • carbamazepine

              carbamazepine will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ergoloid mesylates

              isosorbide dinitrate increases effects of ergoloid mesylates by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

            • ergotamine

              isosorbide dinitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

            • fexinidazole

              fexinidazole will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • ivosidenib

              ivosidenib will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lofexidine

              lofexidine, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              lofexidine, isosorbide dinitrate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • lonafarnib

              hydralazine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • methylergonovine

              isosorbide dinitrate increases effects of methylergonovine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

            • pexidartinib

              hydralazine and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • phenobarbital

              phenobarbital will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pretomanid

              hydralazine, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • tucatinib

              tucatinib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            Monitor Closely (126)

            • acebutolol

              hydralazine increases effects of acebutolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • aceclofenac

              aceclofenac decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • acemetacin

              acemetacin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • aldesleukin

              aldesleukin increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • amifostine

              amifostine, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • arginine

              isosorbide dinitrate, arginine. Mechanism: additive vasodilation. Use Caution/Monitor. Possible hypotension.

            • aspirin

              aspirin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • aspirin rectal

              aspirin rectal decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • atenolol

              hydralazine increases effects of atenolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • avanafil

              avanafil increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • axitinib

              hydralazine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benazepril

              isosorbide dinitrate, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

            • benzphetamine

              hydralazine, benzphetamine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • betaxolol

              hydralazine increases effects of betaxolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • bisoprolol

              hydralazine increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • bosentan

              bosentan will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bretylium

              isosorbide dinitrate, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              hydralazine, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • bupivacaine implant

              isosorbide dinitrate, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

            • carbidopa

              carbidopa increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

            • captopril

              isosorbide dinitrate, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

            • carvedilol

              hydralazine increases effects of carvedilol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

              carvedilol increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • celecoxib

              celecoxib decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • cenobamate

              cenobamate will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • conivaptan

              conivaptan will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crofelemer

              crofelemer increases levels of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • dabrafenib

              dabrafenib will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dapsone topical

              isosorbide dinitrate increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia.

            • dexfenfluramine

              hydralazine, dexfenfluramine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • dexmethylphenidate

              hydralazine, dexmethylphenidate. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • dextroamphetamine

              hydralazine, dextroamphetamine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • diclofenac

              diclofenac decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • diethylpropion

              hydralazine, diethylpropion. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • diflunisal

              diflunisal decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • dobutamine

              hydralazine, dobutamine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • dopamine

              hydralazine, dopamine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • duvelisib

              duvelisib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

              efavirenz will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix decreases levels of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, isosorbide dinitrate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ephedrine

              hydralazine, ephedrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • epinephrine

              hydralazine, epinephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • epoprostenol

              epoprostenol, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • esmolol

              hydralazine increases effects of esmolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • etodolac

              etodolac decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • etravirine

              etravirine will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              hydralazine, fenfluramine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • fenoldopam

              fenoldopam, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • fenoprofen

              fenoprofen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • finerenone

              hydralazine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              hydralazine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • flurbiprofen

              flurbiprofen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • ibuprofen

              ibuprofen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • ibuprofen IV

              ibuprofen IV decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • iloperidone

              iloperidone increases levels of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • iloprost

              hydralazine, iloprost. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • indomethacin

              indomethacin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • isocarboxazid

              hydralazine, isocarboxazid. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • isoproterenol

              hydralazine, isoproterenol. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • istradefylline

              istradefylline will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ivacaftor

              hydralazine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • ketoprofen

              ketoprofen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • ketorolac

              ketorolac decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • ketorolac intranasal

              ketorolac intranasal decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • labetalol

              hydralazine increases effects of labetalol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • lemborexant

              hydralazine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • levodopa

              levodopa increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • linezolid

              hydralazine, linezolid. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • lisdexamfetamine

              hydralazine, lisdexamfetamine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • lomitapide

              hydralazine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lorlatinib

              lorlatinib will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lornoxicam

              lornoxicam decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • maraviroc

              maraviroc, isosorbide dinitrate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • meclofenamate

              meclofenamate decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • mefenamic acid

              mefenamic acid decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • meloxicam

              meloxicam decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • methamphetamine

              hydralazine, methamphetamine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • methylenedioxymethamphetamine

              hydralazine, methylenedioxymethamphetamine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • methylphenidate

              hydralazine, methylphenidate. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • metoprolol

              hydralazine increases effects of metoprolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • midazolam intranasal

              hydralazine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • midodrine

              hydralazine, midodrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • minoxidil

              hydralazine, minoxidil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • mipomersen

              mipomersen, hydralazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mitotane

              mitotane decreases levels of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • nabumetone

              nabumetone decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • nadolol

              hydralazine increases effects of nadolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • nafcillin

              nafcillin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • naproxen

              naproxen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • nebivolol

              hydralazine increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • nitroglycerin rectal

              nitroglycerin rectal, isosorbide dinitrate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              nitroglycerin rectal, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

            • norepinephrine

              hydralazine, norepinephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • primidone

              primidone will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxaprozin

              oxaprozin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • parecoxib

              parecoxib decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • penbutolol

              hydralazine increases effects of penbutolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • phendimetrazine

              hydralazine, phendimetrazine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • phenelzine

              hydralazine, phenelzine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • phentermine

              hydralazine, phentermine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • phenylephrine

              hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • phenylephrine PO

              hydralazine, phenylephrine PO. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • pindolol

              hydralazine increases effects of pindolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • piroxicam

              piroxicam decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • procarbazine

              hydralazine, procarbazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • propranolol

              hydralazine increases effects of propranolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • propylhexedrine

              hydralazine, propylhexedrine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension.

            • pseudoephedrine

              hydralazine, pseudoephedrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • ribociclib

              ribociclib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • salicylates (non-asa)

              salicylates (non-asa) decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • salsalate

              salsalate decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • sotalol

              hydralazine increases effects of sotalol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • stiripentol

              stiripentol, isosorbide dinitrate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sulfasalazine

              sulfasalazine decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • sulindac

              sulindac decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • tadalafil

              tadalafil increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tazemetostat

              tazemetostat will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              hydralazine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • timolol

              hydralazine increases effects of timolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • tetracaine

              tetracaine, isosorbide dinitrate. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

            • tinidazole

              hydralazine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            Minor (14)

            • acetylcysteine (Antidote)

              acetylcysteine (Antidote) increases effects of isosorbide dinitrate by Other (see comment). Minor/Significance Unknown. Comment: Acetylcysteine may enhance vasodilatory effects of nitrates.

            • agrimony

              agrimony increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

            • celiprolol

              hydralazine increases effects of celiprolol by pharmacodynamic synergism. Minor/Significance Unknown.

            • cornsilk

              cornsilk increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

            • diazoxide

              diazoxide, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

            • forskolin

              forskolin increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

            • maitake

              maitake increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).

            • pyridoxine

              hydralazine decreases levels of pyridoxine by unspecified interaction mechanism. Minor/Significance Unknown.

            • pyridoxine (Antidote)

              hydralazine decreases levels of pyridoxine (Antidote) by unspecified interaction mechanism. Minor/Significance Unknown.

            • reishi

              reishi increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

            • rifampin

              rifampin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rifapentine

              rifapentine will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ruxolitinib

              hydralazine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            Isosorbide Dinatrate

            • Flushing
            • Hypotension/orthostatic hypotension
            • Lightheadedness
            • Palpitations
            • Rebound hypertension (uncommon)
            • Syncope
            • Unstable angina tachyarrhythmia
            • Dizziness
            • Headache
            • Restlessness
            • Weakness
            • Nausea
            • Methemoglobinemia (infrequent)

            Hydralazine

            • Hypotension
            • Palpitations
            • Tachycardia
            • Headache
            • Neuropathy
            • Anorexia
            • Diarrhea
            • Nausea
            • Vomiting
            • Agranulocytosis
            • Leukopenia
            • Hepatotoxicity
            • Chest pain
            • Dyspnea
            • Nasal congestion
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            Warnings

            Contraindications

            Allergy to organic nitrates

            Concomitant use with PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, or vardenafil)

            Concomitant use with soluble guanylate cyclase (sGC) stimulators (eg, riociguat)

            Concomitant use can cause severe hypotension, syncope, or myocardial ischemia

            Cautions

            Hydralazine may cause symptomatic lupus erythematosus syndromes; consider discontinuation if clinically appropriate

            May aggravate myocardial ischemia and angina

            Peripheral neuritis may be treated with pyridoxine

            Symptomatic hypotension may occur

            Paradoxical bradycardia may occur

            Use caution in pulmonary hypertension

            Caution in patients with coronary artery disease or tachycardia

            Caution in in suspected right ventricular infarction or acute MI

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            Pregnancy & Lactation

            Pregnancy

            There are no data on use in pregnant women, and insufficient data on its components (hydralazine and isosorbide dinitrate) to assess a drug-associated risk of major birth defects or miscarriage with first trimester use; available published data on hydralazine use in pregnancy during second and third trimesters have not shown association with adverse pregnancy-related outcomes

            Pregnant women with heart failure are at increased risk for preterm birth; clinical classification of heart disease may worsen with pregnancy and lead to maternal death and/or stillbirth

            Animal data

            • Hydralazine hydrochloride is teratogenic in mice at 66 mg/kg and possibly in rabbits at 33 mg/kg (2 and 3 times maximum recommended human dose (MRHD) on a body surface area basis)
            • Isosorbide dinitrate has been shown to cause a dose-related increase in embryo-toxicity (excess mummified pups) in rabbits at 70 mg/kg (12 times the MRHD on a body surface area basis)

            Lactation

            There are no data on presence of drug in human or animal milk, effects on breastfed infant or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.