Unknown.sunitinibMonitor Closely (1)bosentan will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.suvorexantMonitor Closely (1)bosentan will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daytacrolimusMonitor Closely (1)bosentan will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tadalafilMonitor Closely (1)bosentan will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tamoxifenMonitor Closely (2)bosentan will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. bosentan will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tamsulosinMonitor Closely (1)bosentan will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tasimelteonMonitor Closely (1)bosentan will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducerstazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)bosentan will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.temsirolimusMonitor Closely (1)bosentan will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tenapanorMonitor Closely (1)tenapanor decreases levels of bosentan by Other (see comment). Use Caution/Monitor. Comment: Tenapanor (an inhibitor of intestinal uptake transporter, OATP2B1) may reduce the exposure of OATP2B1 substrates.teniposideMonitor Closely (1)bosentan will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.terbinafineMonitor Closely (2)bosentan will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. bosentan will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tetracyclineMonitor Closely (1)bosentan will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tezacaftorSerious - Use Alternative (1)bosentan will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.theophyllineMonitor Closely (1)bosentan will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tiagabineMonitor Closely (1)bosentan will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ticagrelorMonitor Closely (1)bosentan decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.ticlopidineMonitor Closely (1)bosentan will decrease the level or effect of ticlopidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ticlopidine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.tinidazoleMonitor Closely (1)bosentan will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirMonitor Closely (1)bosentan will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. stop bosentan >36 hours prior to PI initiation and restart 10 days after PI initiation at 62.5 mg once daily or every other day.Serious - Use Alternative (1)tipranavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.tivozanibSerious - Use Alternative (1)bosentan will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.tizanidineMinor (1)tizanidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tofacitinibMonitor Closely (1)bosentan will decrease the level or effect of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Loss of, or decreased response to tofacitinib may occur when coadministered with potent CYP3A4 inducerstolbutamideMinor (1)bosentan will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.tolterodineMonitor Closely (1)bosentan will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tolvaptanSerious - Use Alternative (1)bosentan will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.topiramateMinor (1)topiramate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.toremifeneMonitor Closely (1)bosentan decreases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers increase rate of toremifene metabolism, lowering the steady-state concentration in serum.trabectedinSerious - Use Alternative (1)bosentan will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.tramadolMonitor Closely (1)bosentan will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducerstrazodoneSerious - Use Alternative (1)bosentan will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.treprostinilMinor (1)treprostinil increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.triamcinolone acetonide injectable suspensionMonitor Closely (1)bosentan will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.triazolamMonitor Closely (1)bosentan will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.trofinetideSerious - Use Alternative (1)trofinetide will increase the level or effect of bosentan by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.tucatinibSerious - Use Alternative (2)bosentan will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. tucatinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.ubrogepantSerious - Use Alternative (1)bosentan will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ulipristalSerious - Use Alternative (1)bosentan will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.upadacitinibSerious - Use Alternative (1)bosentan will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.valbenazineMonitor Closely (1)bosentan will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.valproic acidMinor (1)valproic acid will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.vandetanibContraindicated (1)bosentan decreases levels of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with potent CYP3A4 inducers; these drugs reduce exposure to vandetanib by up to 40%.vardenafilMonitor Closely (1)bosentan will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.velpatasvirSerious - Use Alternative (1)bosentan will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.vemurafenibMonitor Closely (1)bosentan will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.venetoclaxSerious - Use Alternative (1)bosentan will decrease the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of venetoclax with strong or moderate CYP3A inducers. Consider alternative treatment with agents that have less CYP3A induction.verapamilMonitor Closely (1)bosentan will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)verapamil will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vilazodoneMonitor Closely (1)bosentan decreases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider increasing vilazodone dose up to 2-fold (not to exceed 80 mg/day) when coadministered with strong CYP3A4 inducers for >14 days.vinblastineMinor (1)bosentan will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vincristineMinor (1)bosentan will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vincristine liposomalMinor (1)bosentan will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vinorelbineMinor (1)bosentan will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.voclosporinSerious - Use Alternative (1)bosentan will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)voclosporin will increase the level or effect of bosentan by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.vonoprazanSerious - Use Alternative (1)bosentan will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.vorapaxarSerious - Use Alternative (1)bosentan decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.voriconazoleMonitor Closely (1)bosentan will decrease the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Minor (3)voriconazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. bosentan will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. voriconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vortioxetineMonitor Closely (2)bosentan will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. bosentan decreases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.voxelotorSerious - Use Alternative (2)bosentan will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications). voxelotor will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.voxilaprevirSerious - Use Alternative (1)bosentan will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)bosentan will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.xipamideMonitor Closely (1)xipamide increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor.zafirlukastMinor (2)zafirlukast will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. zafirlukast will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zaleplonMinor (1)bosentan will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zanubrutinibSerious - Use Alternative (2)bosentan will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. bosentan will decrease the level or effect of zanubrutinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. ziprasidoneMinor (1)bosentan will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zolpidemMinor (1)bosentan will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.zonisamideMinor (1)bosentan will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. >10% Hgb decreased; >1 g/dL (57%) Respiratory tract infection (22%) Headache (16%) Edema (11%) Nasopharyngitis (11%) Flushing (10%) Hypotension (10%) 1-10% Chest pain (5%) Syncope (5%) Hypotension (4%) Sinusitis (4%) Arthralgia (4%) Abnormal AST/ALT (4%) Palpitations (4%) Anemia (4%) Postmarketing Reports Unexplained hepatic cirrhosis Liver failure Hypersensitivity, DRESS, and anaphylaxis Thrombocytopenia Rash Jaundice Anemia requiring transfusion Neutropenia and leukopenia Nasal congestion Black Box Warnings Hepatotoxicity 3-fold ULN elevation of ALT and AST in ~11% of patients observed Measure serum aminotransferase levels (and bilirubin if aminotransferase levels elevated) at baseline & then monthly Rare cases of unexplained hepatic cirrhosis reported after prolonged therapy (>12 months) Avoid in patients with elevated aminotransferase levels (>3X ULN) at baseline because monitoring liver injury may be more difficult Elevations of AST/ALT associated with treatment are dose-dependent; elevated