Dosing & Uses
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; may decrease dose to as little as 1/2 tab q8hr if intolerable side effects occur; as soon as side effects subside, effort should be made to titrate up
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; may decrease dose to as little as 1/2 tab q8hr if intolerable side effects occur; as soon as side effects subside, effort should be made to titrate up
Safety and efficacy not established
Heart failure
1 tab PO q8hr; titrate dose to effect; not to exceed 2 tab PO q8hr
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
- 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.
- levoketoconazole
levoketoconazole will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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 (130)
- 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.
- atogepant
hydralazine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- isavuconazonium sulfate
hydralazine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- lenacapavir
lenacapavir will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- 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.
- serdexmethylphenidate/dexmethylphenidate
hydralazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.
hydralazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hypertension. - 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 (18)
- acetazolamide
acetazolamide will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- anastrozole
anastrozole will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- cyclophosphamide
cyclophosphamide will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
- larotrectinib
larotrectinib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.
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
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)
Cautions
Paradoxical bradycardia may occur
Use caution in pulmonary hypertension
Caution in patients with coronary artery disease or tachycardia
Caution in suspected right ventricular infarction or acute MI
Even small doses may cause symptomatic hypotension, particularly with upright posture; most likely to occur in patients who have been volume or salt depleted; correct prior to initiation of therapy
Hydralazine may cause symptomatic lupus erythematosus syndromes; consider discontinuation if clinically appropriate
May cause tachycardia and hypotension, potentially leading to myocardial ischemia and angina, particularly in patients with hypertrophic cardiomyopathy
Associated with peripheral neuritis, which may cause paresthesia, numbness, and tingling that may result from an antipyridoxine effect; add pyridoxine to therapy if such symptoms develop
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.Images
Formulary
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