Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.alprazolamMonitor Closely (1)bosentan will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ambrisentanMinor (1)bosentan will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.amifostineMonitor Closely (1)amifostine, bosentan. 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.amiodaroneMonitor Closely (1)bosentan will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)amiodarone will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.amitriptylineMinor (1)bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.amlodipineMonitor Closely (1)bosentan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for decreased effects of amlodipine (CYP3A4 substrate) if bosentan is initiated/dose increased. Also, monitor toxicities of amlodipine if bosentan is discontinued/dose decreased.amobarbitalMinor (2)amobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. amobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.anastrozoleMinor (1)anastrozole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.apalutamideMonitor Closely (2)apalutamide will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered. apalutamide will decrease the level or effect of bosentan by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.Serious - Use Alternative (1)apalutamide will decrease the level or effect of bosentan 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.apremilastSerious - Use Alternative (1)bosentan will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacyaprepitantMonitor Closely (1)bosentan will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)aprepitant will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.aripiprazoleMonitor Closely (1)bosentan will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.armodafinilMinor (1)armodafinil will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.artemether/lumefantrineContraindicated (1)bosentan will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacyMinor (1)artemether/lumefantrine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.atazanavirSerious - Use Alternative (1)bosentan will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not coadminister unless atazanavir boosted with ritonavirMinor (1)atazanavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.atogepantMonitor Closely (1)bosentan will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.atorvastatinMonitor Closely (1)bosentan will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.avanafilMonitor Closely (1)bosentan will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.avapritinibSerious - Use Alternative (1)bosentan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.avatrombopagMonitor Closely (1)bosentan will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Refer to drug monograph for specific recommendations.axitinibSerious - Use Alternative (1)bosentan decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Selection of concomitant medication with no or minimal CYP3A4 induction potential is recommended.bazedoxifene/conjugated estrogensMonitor Closely (1)bosentan will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bedaquilineSerious - Use Alternative (1)bosentan will decrease the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inducers due to potential for decreased therapeutic effectbelumosudilMonitor Closely (1)bosentan will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.belzutifanMonitor Closely (1)belzutifan will decrease the level or effect of bosentan 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. benzhydrocodone/acetaminophenMonitor Closely (1)bosentan will decrease the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with benzhydrocodone (prodrug of hydrocodone); plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.benzphetamineSerious - Use Alternative (1)bosentan will decrease the level or effect of benzphetamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.bexaroteneMonitor Closely (1)bosentan will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bortezomibMonitor Closely (1)bosentan will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.bosutinibSerious - Use Alternative (1)bosentan decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .brexpiprazoleMonitor Closely (1)bosentan will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.brigatinibSerious - Use Alternative (1)bosentan will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.brimonidineMinor (1)brimonidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.bromocriptineMonitor Closely (1)bosentan will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.budesonideMonitor Closely (1)bosentan will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)budesonide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.buprenorphineMonitor Closely (1)bosentan will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.buprenorphine buccalMonitor Closely (1)bosentan will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.buprenorphine subdermal implantMonitor Closely (1)bosentan will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.buprenorphine transdermalMonitor Closely (1)bosentan will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.buprenorphine, long-acting injectionMonitor Closely (1)bosentan will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.buspironeMonitor Closely (1)bosentan will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.butabarbitalMinor (2)butabarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. butabarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.butalbitalMinor (2)butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cabazitaxelMonitor Closely (1)bosentan will decrease the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of strong CYP3A4 inducers may decrease cabazitaxel concentrations. Avoid coadministration.cabozantinibSerious - Use Alternative (1)bosentan will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.calcifediolMonitor Closely (1)bosentan, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.calcitriolMonitor Closely (1)bosentan will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cannabidiolMonitor Closely (1)cannabidiol will increase the level or effect of bosentan by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.capmatinibSerious - Use Alternative (1)bosentan will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.carbamazepineMonitor Closely (2)bosentan will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. carbamazepine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.carbidopaMonitor Closely (1)carbidopa increases effects of bosentan 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.cariprazineContraindicated (1)bosentan will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.carvedilolMonitor Closely (1)bosentan will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.celecoxibMinor (1)bosentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.cenobamateMonitor Closely (1)cenobamate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.ceritinibMonitor Closely (1)ceritinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)bosentan decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.cevimelineMinor (1)bosentan will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.chloramphenicolMonitor Closely (1)chloramphenicol will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.chlordiazepoxideMonitor Closely (1)bosentan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cholic acidMonitor Closely (1)bosentan increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.cilostazolMonitor Closely (1)bosentan will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cimetidineMonitor Closely (1)cimetidine will increase the