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.imatinibMonitor Closely (1)imatinib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For ED limit tadalafil to max of 2.5 mg/day (for daily use) or 10 mg dose every 72 hr (for use as needed). Avoid concurrent use of tadalafil for pulmonary HTN in patients taking strong CYP3A4 inhibitors.indapamideMonitor Closely (1)tadalafil increases effects of indapamide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.indinavirSerious - Use Alternative (1)indinavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stop tadalafil >24 hours prior to protease inhibitor (PI) initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.irbesartanMonitor Closely (1)tadalafil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For ED limit tadalafil to max of 2.5 mg/day (for daily use) or 10 mg dose every 72 hr (for use as needed). Avoid concurrent use of tadalafil for pulmonary HTN in patients taking strong CYP3A4 inhibitors.isosorbide dinitrateContraindicated (1)isosorbide dinitrate, tadalafil. Mechanism: additive vasodilation. Contraindicated. Contraindicated. Potentially fatal hypotension. Allow 48h after last tadalafil dose before nitrate administration.isosorbide mononitrateContraindicated (1)isosorbide mononitrate, tadalafil. Mechanism: additive vasodilation. Contraindicated. Contraindicated. Potentially fatal hypotension. Allow 48h after last tadalafil dose before nitrate administration.isradipineMonitor Closely (1)tadalafil increases effects of isradipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of tadalafil 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.itraconazoleSerious - Use Alternative (1)itraconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For ED limit tadalafil to max of 2.5 mg/day (for daily use) or 10 mg dose every 72 hr (for use as needed). Avoid concurrent use of tadalafil for pulmonary HTN in patients taking strong CYP3A4 inhibitors.ketoconazoleSerious - Use Alternative (1)ketoconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. labetalolMonitor Closely (1)tadalafil increases effects of labetalol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.lapatinibMonitor Closely (1)lapatinib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.larotrectinibMinor (1)larotrectinib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lenacapavirSerious - Use Alternative (1)lenacapavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Refer to the prescribing information of PDE5 inhibitors for dose recommendations. letermovirMonitor Closely (1)letermovir increases levels of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levoketoconazoleSerious - Use Alternative (1)levoketoconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. lisinoprilMonitor Closely (1)tadalafil increases effects of lisinopril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.lonafarnibSerious - Use Alternative (1)lonafarnib will increase the level or effect of tadalafil 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 tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. losartanMonitor Closely (1)tadalafil increases effects of losartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.lumefantrineMonitor Closely (1)lumefantrine will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.maravirocMonitor Closely (1)maraviroc, tadalafil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.marijuanaMonitor Closely (1)marijuana will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.metolazoneMonitor Closely (1)tadalafil increases effects of metolazone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.metoprololMonitor Closely (1)tadalafil increases effects of metoprolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.metronidazoleMonitor Closely (1)metronidazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mifepristoneMonitor Closely (1)mifepristone will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.minoxidilMonitor Closely (1)tadalafil increases effects of minoxidil by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.mitotaneMonitor Closely (1)mitotane decreases levels of tadalafil 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.nadololMonitor Closely (1)tadalafil increases effects of nadolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nebivololMonitor Closely (1)tadalafil increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For ED limit tadalafil to max of 2.5 mg/day (for daily use) or 10 mg dose every 72 hr (for use as needed). Avoid concurrent use of tadalafil for pulmonary HTN in patients taking strong CYP3A4 inhibitors.nelfinavirSerious - Use Alternative (1)nelfinavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stop tadalafil >24 hours prior to protease inhibitor (PI) initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.nicardipineSerious - Use Alternative (1)nicardipine will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. nifedipineMonitor Closely (2)nifedipine will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Risk of hypotension. tadalafil increases effects of nifedipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.nilotinibMonitor Closely (1)nilotinib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nimodipineMonitor Closely (1)tadalafil increases effects of nimodipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.nirmatrelvir/ritonavirSerious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration if tadalafil used for pulmonary arterial hpertension. Reduce tadalafil dose if used for erectile dysfunction. nisoldipineMonitor Closely (1)tadalafil increases effects of nisoldipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.nitroglycerin IVContraindicated (1)nitroglycerin IV, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin POContraindicated (1)nitroglycerin PO, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin rectalContraindicated (1)tadalafil 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, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin topicalContraindicated (1)nitroglycerin topical, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin transdermalContraindicated (1)nitroglycerin transdermal, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroglycerin translingualContraindicated (1)nitroglycerin translingual, tadalafil. Mechanism: additive vasodilation. Contraindicated. Potentially fatal hypotension.nitroprusside sodiumMonitor Closely (1)nitroprusside sodium, tadalafil. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.olmesartanMonitor Closely (1)tadalafil increases effects of olmesartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.oxcarbazepineMonitor Closely (1)oxcarbazepine will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.pazopanibMonitor Closely (1)pazopanib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.penbutololMonitor Closely (1)tadalafil increases effects of penbutolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.pentobarbitalMonitor Closely (1)pentobarbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.phenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.phenoxybenzamineMonitor Closely (1)tadalafil increases effects of phenoxybenzamine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.phentolamineMonitor Closely (1)tadalafil increases effects of phentolamine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.phenytoinMonitor Closely (1)phenytoin will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.posaconazoleMonitor Closely (1)posaconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.prazosinMonitor Closely (1)tadalafil increases effects of prazosin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.primidoneMonitor Closely (1)primidone will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.propranololMonitor Closely (1)tadalafil increases effects of propranolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.quinaprilMonitor Closely (1)tadalafil increases effects of quinapril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.quinupristin/dalfopristinMonitor Closely (1)quinupristin/dalfopristin will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ramiprilMonitor Closely (1)tadalafil increases effects of ramipril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.ranolazineMinor (1)ranolazine will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates, such as tadalafil.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.rifampinMonitor Closely (1)rifampin will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.riociguatContraindicated (1)tadalafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension; do not administer 24 hr before or within 48hr of each other.ritonavirSerious - Use Alternative (1)ritonavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stop tadalafil >24 hours prior to protease inhibitor (PI) initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.rufinamideMonitor Closely (1)rufinamide will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.sacubitril/valsartanMonitor Closely (1)tadalafil increases effects of sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.sapropterinMonitor Closely (1)sapropterin, tadalafil. Either increases