substrates may require dosage adjustment.tazemetostattazemetostat will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimattecovirimat will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.Minor (2)nirmatrelvir/ritonavirnirmatrelvir/ritonavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Macitentan is metabolized mainly by CYP3A4, but is not a substrate of OATPs. The magnitude of interaction is expected to be low. No dosage adjustment required.sildenafilmacitentan 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.abametapirSerious - Use Alternative (1)abametapir will increase the level or effect of macitentan 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.apalutamideSerious - Use Alternative (1)apalutamide will decrease the level or effect of macitentan 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.atazanavirSerious - Use Alternative (1)atazanavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors bosentanSerious - Use Alternative (1)bosentan will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers carbamazepineSerious - Use Alternative (1)carbamazepine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers cenobamateMonitor Closely (1)cenobamate will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.clarithromycinSerious - Use Alternative (1)clarithromycin will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors conivaptanSerious - Use Alternative (1)conivaptan will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors dabrafenibSerious - Use Alternative (1)dabrafenib will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers darunavirSerious - Use Alternative (1)darunavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors dexamethasoneSerious - Use Alternative (1)dexamethasone will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers duvelisibMonitor Closely (1)duvelisib will increase the level or effect of macitentan 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.efavirenzSerious - Use Alternative (1)efavirenz will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers elagolixMonitor Closely (1)elagolix decreases levels of macitentan 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 DFSerious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors encorafenibMonitor Closely (1)encorafenib, macitentan. 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.enzalutamideSerious - Use Alternative (1)enzalutamide will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers eslicarbazepine acetateSerious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.etravirineSerious - Use Alternative (1)etravirine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers fedratinibMonitor Closely (1)fedratinib will increase the level or effect of macitentan 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 macitentan 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.fosamprenavirSerious - Use Alternative (1)fosamprenavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors fosphenytoinSerious - Use Alternative (1)fosphenytoin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers idelalisibSerious - Use Alternative (1)idelalisib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substratesimatinibSerious - Use Alternative (1)imatinib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors indinavirSerious - Use Alternative (1)indinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors isoniazidSerious - Use Alternative (1)isoniazid will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of macitentan 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 macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors ivosidenibSerious - Use Alternative (1)ivosidenib will decrease the level or effect of macitentan 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 macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of macitentan 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.levoketoconazoleSerious - Use Alternative (1)levoketoconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors lopinavirSerious - Use Alternative (1)lopinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors mitotaneMonitor Closely (1)mitotane decreases levels of macitentan 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.nafcillinSerious - Use Alternative (1)nafcillin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers nefazodoneSerious - Use Alternative (1)nefazodone will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors nelfinavirSerious - Use Alternative (1)nelfinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors nevirapineSerious - Use Alternative (1)nevirapine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers nicardipineSerious - Use Alternative (1)nicardipine will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors nirmatrelvir/ritonavirMinor (1)nirmatrelvir/ritonavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Macitentan is metabolized mainly by CYP3A4, but is not a substrate of OATPs. The magnitude of interaction is expected to be low. No dosage adjustment required.oxcarbazepineSerious - Use Alternative (1)oxcarbazepine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers pentobarbitalSerious - Use Alternative (1)pentobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers phenobarbitalSerious - Use Alternative (1)phenobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers phenytoinSerious - Use Alternative (1)phenytoin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers posaconazoleSerious - Use Alternative (1)posaconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors primidoneSerious - Use Alternative (1)primidone will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers quinidineSerious - Use Alternative (1)quinidine will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors rifabutinSerious - Use Alternative (1)rifabutin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers rifampinSerious - Use Alternative (1)rifampin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers rifapentineSerious - Use Alternative (1)rifapentine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers ritonavirSerious - Use Alternative (1)ritonavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors rucaparibMonitor Closely (1)rucaparib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.saquinavirSerious - Use Alternative (1)saquinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors sildenafilMinor (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.sparsentanContraindicated (1)sparsentan, macitentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).stiripentolMonitor Closely (1)stiripentol, macitentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with