dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.fesoterodinebosentan will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.flibanserinbosentan will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.fludrocortisonebosentan will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fluoxetinefluoxetine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.flurazepambosentan will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fluvoxaminefluvoxamine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.fosaprepitantbosentan will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosphenytoinbosentan will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.fostamatinibbosentan will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fostemsavirfostemsavir will increase the level or effect of bosentan by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir. gefitinibbosentan will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.glecaprevir/pibrentasvirbosentan will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.glecaprevir/pibrentasvir will increase the level or effect of bosentan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3glyburidebosentan decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.guanfacinebosentan will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.haloperidolbosentan will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.hydrocodonebosentan will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depressionhydrocortisonebosentan will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.hydroxyprogesterone caproate (DSC)bosentan will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ifosfamidebosentan increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.iloperidonebosentan will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.iloperidone increases levels of bosentan 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.imatinibimatinib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.isoniazidisoniazid will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.isosorbide dinitratebosentan will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.isosorbide mononitratebosentan will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.istradefyllineistradefylline will increase the level or effect of bosentan 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.itraconazoleitraconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bosentan will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ixabepilonebosentan will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ketoconazoleketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lapatinibbosentan will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.larotrectiniblarotrectinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lenacapavirlenacapavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) 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. lesinuradbosentan will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.letermovirletermovir increases levels of bosentan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.levamlodipinebosentan will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.levodopalevodopa increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.levoketoconazolelevoketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levonorgestrel intrauterinebosentan decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levonorgestrel oralbosentan decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levonorgestrel oral/ethinylestradiol/ferrous bisglycinatebosentan will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.linagliptinbosentan will decrease the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer.lomitapidebosentan will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lopinavirbosentan will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.loratadinebosentan will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lorlatiniblorlatinib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.losartanbosentan will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.bosentan will decrease the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lumacaftor/ivacaftorlumacaftor/ivacaftor, bosentan. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .lurasidonebosentan decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. It may be necessary to increase the lurasidone dose after chronic treatment (ie, 7 days or more) with moderate CYP3A inducers.maravirocbosentan will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.marijuanabosentan will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.medroxyprogesteronebosentan will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.mefloquinebosentan will decrease the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mestranolbosentan will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.methadonebosentan will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.methylprednisolonebosentan will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.midazolambosentan will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mifepristonebosentan will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers have not been studied, coadministration not recommended by manufacturermirtazapinebosentan will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mitotanemitotane decreases levels of bosentan 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.naldemedinebosentan will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Simulation using physiologically-based pharmacokinetic modeling suggests that concomitant use of moderated CYP3A4 inducers decrease exposure to naldemedine. The clinical consequence of this decreased exposure is unknown.nateglinidebosentan will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.nefazodonenefazodone will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bosentan will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nevirapinebosentan will decrease the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nicardipinebosentan will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nifedipinebosentan will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.nilotinibbosentan will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nisoldipinebosentan will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nitisinonenitisinone will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.norgestrelbosentan will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methodsoliceridinebosentan will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.osilodrostatbosentan will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.ospemifenebosentan decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bosentan decreases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.oxycodonebosentan decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.palbociclibbosentan will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.parecoxibbosentan will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.paricalcitolbosentan will decrease the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.pazopanibbosentan will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.peginterferon alfa 2bpeginterferon alfa 2b decreases levels of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .phenytoinbosentan will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.pimavanserinbosentan will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.pitolisantbosentan will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.polatuzumab vedotinbosentan will decrease the level or effect of polatuzumab