enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenytoin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pimavanserinMonitor Closely (1)bosentan 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.pimozideMinor (1)bosentan will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pioglitazoneMinor (1)bosentan will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.piroxicamMinor (1)bosentan will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.pirtobrutinibSerious - Use Alternative (1)bosentan will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).pitolisantMonitor Closely (1)bosentan 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 vedotinMonitor Closely (1)bosentan will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.pomalidomideSerious - Use Alternative (1)bosentan decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ponatinibSerious - Use Alternative (1)bosentan decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.posaconazoleMinor (1)posaconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pralsetinibSerious - Use Alternative (1)bosentan will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.praziquantelContraindicated (1)bosentan decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.prednisoloneMonitor Closely (1)bosentan will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.prednisoneMonitor Closely (1)bosentan will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)prednisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pretomanidSerious - Use Alternative (1)bosentan will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.primaquineMonitor Closely (1)bosentan will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.primidoneMinor (2)primidone will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. primidone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.progesterone intravaginal gelSerious - Use Alternative (1)bosentan will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.progesterone micronizedSerious - Use Alternative (1)bosentan will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.progesterone, naturalSerious - Use Alternative (1)bosentan will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.propafenoneMinor (1)bosentan will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.quazepamMonitor Closely (1)bosentan will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.quetiapineMonitor Closely (1)bosentan will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.quinidineMonitor Closely (1)bosentan will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.quinineMinor (1)bosentan will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.quinupristin/dalfopristinMinor (1)quinupristin/dalfopristin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rabeprazoleMinor (1)bosentan will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ramelteonMinor (2)bosentan will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. bosentan will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ranolazineSerious - Use Alternative (1)bosentan will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.regorafenibContraindicated (1)bosentan, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.reishiMinor (1)reishi increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.repaglinideMonitor Closely (1)bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ribociclibMonitor Closely (2)ribociclib 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 ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of ribociclib with strong CYP3A inducers should be avoided.rifabutinMonitor Closely (2)rifabutin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. bosentan will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifampinMonitor Closely (2)rifampin will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. rifampin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifapentineMinor (2)rifapentine will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. rifapentine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rimegepantSerious - Use Alternative (1)bosentan will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.riociguatMonitor Closely (1)bosentan will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentripretinibSerious - Use Alternative (1)bosentan will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.ritonavirSerious - Use Alternative (1)bosentan will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. 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.Minor (1)ritonavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rivaroxabanMonitor Closely (1)bosentan will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.roflumilastContraindicated (1)bosentan will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessromidepsinSerious - Use Alternative (1)bosentan will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong 3A4 inducers should be avoided if possible.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.rufinamideMinor (1)rufinamide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ruxolitinibMonitor Closely (1)bosentan will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ruxolitinib topicalMonitor Closely (1)bosentan will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.saquinavirMonitor Closely (1)saquinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)bosentan will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. 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.saxagliptinMinor (1)bosentan will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.secobarbitalMinor (2)secobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. secobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.selpercatinibSerious - Use Alternative (1)bosentan will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.selumetinibSerious - Use Alternative (1)bosentan will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.shepherd's purseMinor (1)shepherd's purse, bosentan. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.sildenafilMonitor Closely (1)bosentan will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levelssilodosinSerious - Use Alternative (1)bosentan will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.simvastatinSerious - Use Alternative (1)bosentan will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.siponimodSerious - Use Alternative (1)bosentan will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.sirolimusSerious - Use Alternative (1)bosentan will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.sofosbuvir/velpatasvirSerious - Use Alternative (1)bosentan will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.solifenacinMonitor Closely (1)bosentan will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.sonidegibSerious - Use Alternative (1)bosentan will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.sorafenibMonitor Closely (1)bosentan decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.sotorasibSerious - Use Alternative (1)bosentan will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.sparsentanContraindicated (1)sparsentan, bosentan. 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).St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.stiripentolMonitor Closely (1)stiripentol, bosentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.Serious - Use Alternative (1)bosentan will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.sufentanilMinor (1)bosentan will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.sufentanil SLMonitor Closely (1)bosentan decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.sulfamethoxazoleMinor (1)sulfamethoxazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance