for which elevated plasma concentrations are associated with serious and/or life-threatening events; contraindication applies to chronic administration of sildenafil for PAH; for ED, not to exceed 25 mg in 48 hr.encorafenibMonitor Closely (1)encorafenib, sildenafil. 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.enzalutamideMonitor Closely (1)enzalutamide will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsepoprostenolMonitor Closely (1)epoprostenol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.erythromycin baseMonitor Closely (1)erythromycin base will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 25 mg in patients treated with erythromycin.erythromycin ethylsuccinateMonitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 25 mg in patients treated with erythromycin.erythromycin lactobionateMonitor Closely (1)erythromycin lactobionate will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 25 mg in patients treated with erythromycin.erythromycin stearateMonitor Closely (1)erythromycin stearate will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 25 mg in patients treated with erythromycin.eslicarbazepine acetateSerious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsesmololMonitor Closely (1)esmolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.etravirineMonitor Closely (1)etravirine will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsfedratinibMonitor Closely (1)fedratinib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.fexinidazoleSerious - Use Alternative (1)fexinidazole will increase the level or effect of sildenafil 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.fezolinetantContraindicated (1)sildenafil will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitorsfluconazoleMonitor Closely (1)fluconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosamprenavirMonitor Closely (1)fosamprenavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.fosaprepitantMonitor Closely (1)fosaprepitant will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosphenytoinMonitor Closely (1)fosphenytoin will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsglyceryl trinitrate prSerious - Use Alternative (1)glyceryl trinitrate pr, sildenafil. Mechanism: additive vasodilation. Avoid or Use Alternate Drug. Potentially fatal hypotension.grapefruitMonitor Closely (1)grapefruit will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.griseofulvinMonitor Closely (1)griseofulvin will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.hydrocortisoneMonitor Closely (1)hydrocortisone will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.idelalisibMonitor Closely (1)idelalisib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of sildenafil with strong CYP3A4 inhibitors is not recommended. If using Viagra, consider decreasing starting dose.iloperidoneMonitor Closely (1)iloperidone increases levels of sildenafil 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.indinavirMonitor Closely (1)indinavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If used concomitantly, monitor for toxicities. Patients receiving indinavir with ritonavir should receive not more than 25 mg of sildenafil for treatment of erectile dysfunction in a 48-hour period, and patients receiving other protease inhibitors should use a lower initial sildenafil dose of 25 mg.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.isosorbide dinitrateContraindicated (1)isosorbide dinitrate, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.isosorbide mononitrateContraindicated (1)isosorbide mononitrate, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of sildenafil 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.itraconazoleMonitor Closely (1)itraconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Not recommended during and 2 weeks after itraconazole treatment when sildenafil is used for pulmonary arterial hypertension.ivosidenibSerious - Use Alternative (1)ivosidenib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.ketoconazoleSerious - Use Alternative (1)ketoconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inhibitors and sildenafil (for pulmonary arterial hypertension) is not recommended. When used for erectile dysfunction, consider reducing initial sildenafil dose of 25 mg in patients also taking a strong CYP3A4 inhibitor and monitor for sildenafil toxicities (eg, dyspepsia, headache, hypotension).labetalolMonitor Closely (1)labetalol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.Minor (1)sildenafil increases effects of labetalol by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.lapatinibMonitor Closely (1)lapatinib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.larotrectinibMinor (1)larotrectinib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lenacapavirSerious - Use Alternative (1)lenacapavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Refer to the prescribing information of PDE5 inhibitors for dose recommendations. lesinuradMonitor Closely (1)lesinurad decreases levels of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.letermovirMonitor Closely (1)letermovir increases levels of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levamlodipineMonitor Closely (1)levamlodipine, sildenafil. anti-hypertensive channel blocking. Use Caution/Monitor. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.levoketoconazoleSerious - Use Alternative (1)levoketoconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inhibitors and sildenafil (for pulmonary arterial hypertension) is not recommended. When used for erectile dysfunction, consider reducing initial sildenafil dose of 25 mg in patients also taking a strong CYP3A4 inhibitor and monitor for sildenafil toxicities (eg, dyspepsia, headache, hypotension).lonafarnibSerious - Use Alternative (1)lonafarnib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.lopinavirSerious - Use Alternative (1)lopinavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.lorlatinibMonitor Closely (1)lorlatinib will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.macitentanMinor (1)macitentan increases levels of sildenafil by unspecified interaction mechanism. Minor/Significance Unknown. Systemic exposure of steady-state sildenafil (20 mg TID) increased by 15% during coadministration of macitentan (10 mg/day); this change is not considered clinically relevant.maravirocMonitor Closely (1)maraviroc, sildenafil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.mavacamtenMonitor Closely (1)sildenafil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose. metoprololMonitor Closely (1)metoprolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.miconazole vaginalMonitor Closely (1)miconazole vaginal will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mifepristoneSerious - Use Alternative (1)mifepristone will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.mitotaneSerious - Use Alternative (1)mitotane decreases levels of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levels.nafcillinSerious - Use Alternative (1)nafcillin will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsnebivololMonitor Closely (1)nebivolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.nelfinavirContraindicated (1)nelfinavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelsnifedipineMonitor Closely (1)nifedipine will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nilotinibMonitor Closely (1)nilotinib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nirmatrelvirContraindicated (1)nirmatrelvir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.nirmatrelvir/ritonavirContraindicated (1)nirmatrelvir/ritonavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration contraindicated if sildenafil used for pulmonary arterical hypertension. Reduce sildenafil dose if used for erectile dysfunction.nitroglycerin IVContraindicated (1)nitroglycerin IV, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin POContraindicated (1)nitroglycerin PO, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin rectalContraindicated (1)sildenafil increases effects of nitroglycerin rectal by additive vasodilation. Contraindicated. Use of nitroglycerin within a few days of PDE5 inhibitors is contraindicated. PDE5 inhibitors have been shown to potentiate the hypotensive effects of organic nitrates.nitroglycerin sublingualContraindicated (1)nitroglycerin sublingual, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin topicalContraindicated (1)nitroglycerin topical, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin transdermalContraindicated (1)nitroglycerin transdermal, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin translingualContraindicated (1)nitroglycerin translingual, sildenafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroprusside sodiumMonitor Closely (1)nitroprusside sodium, sildenafil. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)Serious - Use Alternative (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If used concomitantly, monitor for toxicities. Patients receiving indinavir with ritonavir should receive not more than 25 mg of sildenafil for treatment of erectile dysfunction in a 48-hour period, and patients receiving other protease inhibitors should use a lower initial sildenafil dose of 25 mg. Patient taking sildenafil for PAH with ritonavir is not recommended.oxcarbazepineSerious - Use Alternative (1)oxcarbazepine will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelspenbutololMonitor Closely (1)penbutolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor.