bosentan (Rx)

Pulmonary Arterial Hypertension (PAH)

Indicated to improve exercise ability and decrease worsening of PAH; effectiveness shown in NYHA II-IV, idiopathic or heritable PAH, connective tissue diseases that result in PAH, and PAH associated with congenital heart disease with left-to-right shunts

<40 kg: Maintain dose at 62.5 mg PO q12hr

>40 kg: 62.5 mg PO q12hr for 4 weeks and then increased to maintenance dosage 125 mg PO q12hr

Discontinuation of treatment: Consider a reduction in dosage to 62.5 mg PO q12hr for 3-7 days

See Administration

Dosage Modifications

Elevated ALT/AST levels

• Discontinue if elevated ALT/AST levels are accompanied with clinical symptoms of hepatotoxicity (eg, nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy, fatigue) or bilirubin ≥2X ULN; reintroduction studies have not been established
• Confirm test, if confirmed, reduce/hold dose as described below
• >12 years and >40 kg: Reduce dose to 62.5 mg PO q12hr or interrupt treatment and monitor liver tests at least q2weeks; if levels return to pretreatment values, continue or reintroduce treatment at 62.5mg PO q12hr; reassess levels within 3 days

• >5 and <8X ULN

  • Interrupt treatment and monitor AST/ALT at least q2weeks
  • >12 years and >40 kg: If levels return to pretreatment values, consider reintroducing dose to 62.5 mg PO q12hr; reassess levels within 3 days

• >8X ULN

  • Stop treatment; reintroduction should not be considered

Liver impairment

• Mild: No dose adjustment required
• Moderate or severe: Avoid use
• AST/ALT >3X ULN: Avoid use

Coadministration with ritonavir

• Have been receiving ritonavir for at least 10 days: Initiate bosentan at the recommended starting dose qDay or every other day based on tolerability
• Have been receiving bosentan: Discontinue bosentan <36 hr prior to initiating ritonavir; resume bosentan at recommended initial dose qDay or every other day after at least 10 days of ritonavir treatment

Idiopathic Pulmonary Fibrosis (Orphan)

Orphan indication sponsor

• Actelion Pharmaceuticals Ltd; Gewerbestrasse 16, CH-4123; Switzerland

Systemic Sclerosis (Orphan)

Reduction of the number (treatment) of new digital ulcers in patients with systemic sclerosis

Orphan indication sponsor

• Actelion Pharmaceuticals Ltd; Gewerbestrasse 16, CH-4123; Switzerland

Dosage Strengths & Forms

tablet, film-coated

• 62.5mg
• 125 mg

tablet, for oral suspension

• 32 mg

Pulmonary Arterial Hypertension (PAH)

Indicated in children and adolescents aged ≥3 years with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR)

See Administration

<3 years: Safety and efficacy not established

3 to ≥12 years

• ≥4-8 kg: Maintain dose at 16 mg PO q12hr
• >8-16 kg: Maintain dose at 32 mg PO q12hr
• >16-24 kg: Maintain dose at 48 mg PO q12hr
• >24-40 kg: Maintain dose at 64 mg PO q12hr

>12 years

• <40 kg: Maintain dose at 62.5mg PO q12hr
• >40 kg: 62.5mg PO q12hr initially for 4 weeks, then increase to maintenance dose 125 mg PO q12hr

Dosage Modifications

Discontinue if elevated ALT/AST levels are accompanied with clinical symptoms of hepatotoxicity (eg, nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy, fatigue) or bilirubin ≥2X ULN; reintroduction should not be considered

Elevated ALT/AST levels

• Confirm test, if confirmed

• >3 and <5X ULN

  • >12 years and >40 kg: Reduce dose to 62.5 mg PO q12hr or interrupt treatment and monitor liver tests at least q2weeks; if levels return to pretreatment values, continue or reintroduce treatment at 62.5mg PO q12hr; reassess levels within 3 days
  • ≥3-12 years and <40 kg: Interrupt treatment; if levels return to pretreatment values, consider reintroduction of initial dose; reassess levels within 3 days

• >5 and <8X ULN

  • Interrupt treatment and monitor AST/ALT at least q2weeks
  • >12 years and >40 kg: If levels return to pretreatment values, consider reintroducing dose to 62.5 mg PO q12hr; reassess levels within 3 days
  • ≥3-12 years and <40 kg: If levels return to pretreatment values, consider reintroduction of initial dose; reassess levels within 3 days

• >8X ULN

  • Stop treatment; reintroduction should not be considered

Coadministration with ritonavir

• Have been receiving ritonavir for at least 10 days: Initiate bosentan at the recommended starting dose qDay or every other day based on tolerability
• Have been receiving bosentan: Discontinue bosentan <36hr prior to initiation of ritonavir treatment; resume bosentan at recommended initial dose qDay or every other day after at least 10 days of ritonavir treatment

Contraindicated (23)

• artemether/lumefantrine

  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 efficacy

• cariprazine

  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.

• cobimetinib

  bosentan will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• cyclosporine

  cyclosporine will increase the level or effect of bosentan by Other (see comment). Contraindicated. may increase plasma concentrations of OATP substrates

• dienogest/estradiol valerate

  bosentan will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

• doravirine

  bosentan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  bosentan decreases levels of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May lead to loss of virologic response and possible resistance.

• fostemsavir

  bosentan will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• glyburide

  bosentan, glyburide. Either decreases levels of the other by increasing metabolism. Contraindicated.
  
  bosentan, glyburide. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration increases risk of liver enzyme elevations; alternative hypoglycemic agents should be considered.

• isavuconazonium sulfate

  bosentan will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lonafarnib

  bosentan will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lorlatinib

  bosentan will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• lumacaftor/ivacaftor

  bosentan will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.

• lumefantrine

  bosentan will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

• mavacamten

  bosentan will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• naloxegol

  bosentan will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of naloxegol with strong CYP3A4 inducers is not recommended

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  bosentan will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers may reduce partiaprevir and ritonavir levels, and therefore decreased efficacy of Viekira Pak

• panobinostat

  bosentan decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

• praziquantel

  bosentan decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

• regorafenib

  bosentan, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.

• roflumilast

  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 effectiveness

• sparsentan

  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).

• vandetanib

  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%.

Serious - Use Alternative (130)

• abametapir

  abametapir will increase the level or effect of bosentan 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.

• abemaciclib

  bosentan will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• alpelisib

  bosentan will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

• apalutamide

  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.

• apremilast

  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 efficacy

• atazanavir

  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 ritonavir

• avapritinib

  bosentan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• axitinib

  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.

• bedaquiline

  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 effect

• benzphetamine

  bosentan will decrease the level or effect of benzphetamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bosutinib

  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% .

• brigatinib

  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.

• cabozantinib

  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.

• capmatinib

  bosentan will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ceritinib

  bosentan decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cobicistat

  cobicistat will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Bosentan dose reduction required

• copanlisib

  bosentan will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cyclosporine

  cyclosporine will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dabrafenib

  bosentan decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• daridorexant

  bosentan will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darunavir

  bosentan will decrease the level or effect of darunavir 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.

• deflazacort

  bosentan will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• delavirdine

  bosentan will decrease the level or effect of delavirdine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine

  bosentan will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  bosentan will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dronedarone

  bosentan will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• duvelisib

  bosentan will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• elacestrant

  bosentan will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elbasvir/grazoprevir

  bosentan will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

• eliglustat

  bosentan will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

• elvitegravir

  bosentan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• encorafenib

  bosentan will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• entrectinib

  bosentan will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  bosentan will decrease the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP2C9 or CYP3A4 inducers with erdafitinib.

• ergotamine

  bosentan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin base

  bosentan will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  bosentan will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  bosentan will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  bosentan will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethinylestradiol

  bosentan will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

• everolimus

  bosentan will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fedratinib

  bosentan will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• fexinidazole

  bosentan will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.
  
  fexinidazole will increase the level or effect of bosentan 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.

• finerenone

  bosentan will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosamprenavir

  bosentan will decrease the level or effect of fosamprenavir 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.

• ganaxolone

  bosentan will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• glasdegib

  bosentan will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• ibrutinib

  bosentan decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• idelalisib

  bosentan will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure
  
  idelalisib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• indinavir

  bosentan will decrease the level or effect of indinavir 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.

• infigratinib

  bosentan will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  bosentan will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  bosentan will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• istradefylline

  bosentan will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• ivabradine

  bosentan will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

• ivacaftor

  bosentan decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

• ivosidenib

  bosentan will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.
  
  ivosidenib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixazomib

  bosentan will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• larotrectinib

  bosentan will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• lefamulin

  bosentan will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  bosentan will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lenacapavir

  bosentan will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  bosentan will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  leniolisib will increase the level or effect of bosentan by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates

• lofexidine

  lofexidine, bosentan. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

• lopinavir

  lopinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lovastatin

  bosentan will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumateperone

  bosentan will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  bosentan will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  bosentan will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• macitentan

  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

• midostaurin

  bosentan will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  mifepristone will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mobocertinib

  bosentan will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  bosentan will decrease the level or effect of nelfinavir 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.

• neratinib

  bosentan will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• netupitant/palonosetron

  bosentan will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

• nirmatrelvir

  nirmatrelvir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of nirmatrelvir/ritonavir for 5 days may result in significant increases bosentan trough concentrations. Discontinue bosentan at least 36 hr before initiating nirmatrelvir/ritonavir. May resume bosentan 10 days after initiating nirmatrelvir/ritonavir.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of nirmatrelvir/ritonavir for 5 days may result in significant increases bosentan trough concentrations. Discontinue bosentan at least 36 hr before initiating nirmatrelvir/ritonavir. May resume bosentan 10 days after initiating nirmatrelvir/ritonavir.

• norethindrone

  bosentan will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• norgestrel

  bosentan will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• olaparib

  bosentan will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inducers cannot be avoided, be aware of a potential for decreased efficacy of olaparib

• olutasidenib

  bosentan will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  bosentan will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• osimertinib

  bosentan will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• pemigatinib

  bosentan will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• perampanel

  bosentan will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  bosentan will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pomalidomide

  bosentan decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ponatinib

  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.

• pralsetinib

  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.

• pretomanid

  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.

• progesterone intravaginal gel

  bosentan will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone micronized

  bosentan will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone, natural

  bosentan will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ranolazine

  bosentan will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rimegepant

  bosentan will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ripretinib

  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.

• ritonavir

  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.

• romidepsin

  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.

• saquinavir

  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.

• selpercatinib

  bosentan will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  bosentan will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• silodosin

  bosentan will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  bosentan will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  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.

• sirolimus

  bosentan will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sofosbuvir/velpatasvir

  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.

• sonidegib

  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.

• sotorasib

  bosentan will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  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.

• tazemetostat

  bosentan will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tezacaftor

  bosentan will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tipranavir

  tipranavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tivozanib

  bosentan will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tolvaptan

  bosentan will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trabectedin

  bosentan will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trazodone

  bosentan will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trofinetide

  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.

• tucatinib

  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.

• ubrogepant

  bosentan will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  bosentan will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  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.

• velpatasvir

  bosentan will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• venetoclax

  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.

• voclosporin

  bosentan will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  bosentan will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vorapaxar

  bosentan decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voxelotor

  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.

• voxilaprevir

  bosentan will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• zanubrutinib

  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.

Monitor Closely (241)

• abiraterone

  bosentan decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

• acalabrutinib

  bosentan will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aldesleukin

  aldesleukin increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• almotriptan

  bosentan will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alpelisib

  alpelisib will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• alprazolam

  bosentan will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amifostine

  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.

• amiodarone

  bosentan will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amlodipine

  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.

• apalutamide

  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.

• aprepitant

  bosentan will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aripiprazole

  bosentan will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atogepant

  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.

• atorvastatin

  bosentan will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avanafil

  bosentan will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avatrombopag

  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.

• bazedoxifene/conjugated estrogens

  bosentan will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• belumosudil

  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.

• belzutifan

  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/acetaminophen

  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.

• bexarotene

  bosentan will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bortezomib

  bosentan will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexpiprazole

  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.

• bromocriptine

  bosentan will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide

  bosentan will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine

  bosentan will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine buccal

  bosentan will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine subdermal implant

  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 transdermal

  bosentan will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine, long-acting injection

  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.

• buspirone

  bosentan will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cabazitaxel

  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.

• calcifediol

  bosentan, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

• calcitriol

  bosentan will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cannabidiol

  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.

• carbamazepine

  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.

• carbidopa

  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.

• carvedilol

  bosentan will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• cenobamate

  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.

• ceritinib

  ceritinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloramphenicol

  chloramphenicol will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• chlordiazepoxide

  bosentan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cholic acid

  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.

• cilostazol

  bosentan will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cimetidine

  cimetidine will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinacalcet

  bosentan will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• citalopram

  bosentan will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clarithromycin

  clarithromycin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clonazepam

  bosentan will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clopidogrel

  bosentan will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  bosentan will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clozapine

  bosentan will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cobicistat

  bosentan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Bosentan dose reduction required. Refer to the prescribing information of bosentan and cobicistat for recommended dosage adjustments.

• colchicine

  bosentan will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  bosentan will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  bosentan will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens, vaginal

  bosentan will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cortisone

  bosentan will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  crizotinib increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• crofelemer

  crofelemer increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• dabrafenib

  dabrafenib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dantrolene

  bosentan will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darifenacin

  bosentan will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dasatinib

  bosentan will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  deferasirox will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dexamethasone

  bosentan will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam

  bosentan will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam intranasal

  bosentan will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.

• diltiazem

  diltiazem 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 diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxorubicin

  bosentan will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxorubicin liposomal

  bosentan will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dronabinol

  bosentan will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  bosentan will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• efavirenz

  efavirenz will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elagolix

  bosentan will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  elagolix will decrease the level or effect of bosentan 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.

• eletriptan

  bosentan will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elvitegravir

  elvitegravir, bosentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases bosentan levels, and bosentan decreases elvitegravir levels; if elvitegravir received for >10 days, start bosentan at 62.5 mg/day or every other day; if patient taking bosentan and starting elvitegravir, discontinue bosentan at least 36 hr beforehand, may resume bosentan at 62.5 mg/day or every other day after 10 days.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; dosage modification required for bosentan.

• encorafenib

  encorafenib, bosentan. 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.
  
  encorafenib will increase the level or effect of bosentan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

• enzalutamide

  bosentan will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  enzalutamide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erlotinib

  bosentan will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  erythromycin base will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• esomeprazole

  bosentan will decrease the level or effect of esomeprazole by increasing metabolism. Use Caution/Monitor.
  
  bosentan will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol

  bosentan will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  bosentan will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  bosentan will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens esterified

  bosentan will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  bosentan will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eszopiclone

  bosentan will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethosuximide

  bosentan will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethotoin

  bosentan will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etonogestrel

  bosentan will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etoposide

  bosentan will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  bosentan will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  bosentan will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• exemestane

  bosentan will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

• fedratinib

  fedratinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felbamate

  bosentan will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• felodipine

  bosentan will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fentanyl

  bosentan will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl intranasal

  bosentan will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl transdermal

  bosentan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl transmucosal

  bosentan will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fesoterodine

  bosentan will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flibanserin

  bosentan 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.

• fludrocortisone

  bosentan will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  fluoxetine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• flurazepam

  bosentan will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluvoxamine

  fluvoxamine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fosaprepitant

  bosentan will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosphenytoin

  bosentan will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fostamatinib

  bosentan will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

  fostemsavir 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.

• gefitinib

  bosentan 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/pibrentasvir

  bosentan 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 OATP1B3

• glyburide

  bosentan decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

• guanfacine

  bosentan 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.

• haloperidol

  bosentan will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydrocodone

  bosentan 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 depression

• hydrocortisone

  bosentan 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.

• ifosfamide

  bosentan 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.

• iloperidone

  bosentan 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.

• imatinib

  imatinib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• isoniazid

  isoniazid will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• isosorbide dinitrate

  bosentan will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isosorbide mononitrate

  bosentan will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  istradefylline 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.

• itraconazole

  itraconazole 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.

• ixabepilone

  bosentan will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketoconazole

  ketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lapatinib

  bosentan will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• larotrectinib

  larotrectinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lenacapavir

  lenacapavir 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.

• lesinurad

  bosentan will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• letermovir

  letermovir 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.

• levamlodipine

  bosentan 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.

• levodopa

  levodopa increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levoketoconazole

  levoketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel intrauterine

  bosentan decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral

  bosentan decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  bosentan 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.

• linagliptin

  bosentan 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.

• lomitapide

  bosentan will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lopinavir

  bosentan will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loratadine

  bosentan will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lorlatinib

  lorlatinib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• losartan

  bosentan 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/ivacaftor

  lumacaftor/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. .

• lurasidone

  bosentan 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.

• maraviroc

  bosentan will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• marijuana

  bosentan will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• medroxyprogesterone

  bosentan 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.

• mefloquine

  bosentan will decrease the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mestranol

  bosentan will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methadone

  bosentan will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methylprednisolone

  bosentan will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midazolam

  bosentan will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mifepristone

  bosentan 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 manufacturer

• mirtazapine

  bosentan will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mitotane

  mitotane 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.

• naldemedine

  bosentan 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.

• nateglinide

  bosentan will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nefazodone

  nefazodone 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.

• nevirapine

  bosentan will decrease the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  bosentan will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  bosentan will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• nilotinib

  bosentan will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nisoldipine

  bosentan will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nitisinone

  nitisinone 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.

• oliceridine

  bosentan 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.

• osilodrostat

  bosentan 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.

• ospemifene

  bosentan 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.

• oxycodone

  bosentan decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• palbociclib

  bosentan will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• parecoxib

  bosentan will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• paricalcitol

  bosentan will decrease the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pazopanib

  bosentan will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• peginterferon alfa 2b

  peginterferon 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. .

• phenytoin

  bosentan will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pimavanserin

  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.

• pitolisant

  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 vedotin

  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.

• prednisolone

  bosentan will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• prednisone

  bosentan will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primaquine

  bosentan will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quazepam

  bosentan will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quetiapine

  bosentan will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

  bosentan will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• repaglinide

  bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ribociclib

  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.
  
  ribociclib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  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.

• rifampin

  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.

• riociguat

  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 adjustment

• rivaroxaban

  bosentan will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rucaparib

  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.

• ruxolitinib

  bosentan will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib topical

  bosentan will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• saquinavir

  saquinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• sildenafil

  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 levels

• solifenacin

  bosentan will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sorafenib

  bosentan decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• St John's Wort

  St John's Wort will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• stiripentol

  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.

• sufentanil SL

  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.

• sunitinib

  bosentan will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  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/day

• tacrolimus

  bosentan will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  bosentan will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tamoxifen

  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.

• tamsulosin

  bosentan will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tasimelteon

  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 inducers

• tazemetostat

  tazemetostat will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  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.

• temsirolimus

  bosentan will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tenapanor

  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.

• teniposide

  bosentan will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbinafine

  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.

• tetracycline

  bosentan will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• theophylline

  bosentan will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tiagabine

  bosentan will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ticagrelor

  bosentan decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.

• ticlopidine

  bosentan will decrease the level or effect of ticlopidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tinidazole

  bosentan will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  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.

• tofacitinib

  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 inducers

• tolterodine

  bosentan will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• toremifene

  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.

• tramadol

  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 inducers

• triamcinolone acetonide injectable suspension

  bosentan will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  bosentan will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• valbenazine

  bosentan will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vardenafil

  bosentan will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vemurafenib

  bosentan will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• verapamil

  bosentan will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilazodone

  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.

• voriconazole

  bosentan will decrease the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• vortioxetine

  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.
  
  bosentan will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• warfarin

  bosentan will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• xipamide

  xipamide increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor.

Minor (135)

• acetazolamide

  acetazolamide will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  agrimony increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• alfentanil

  bosentan will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

  bosentan will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alosetron

  bosentan will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  bosentan will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ambrisentan

  bosentan will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amiodarone

  amiodarone will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amitriptyline

  bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amobarbital

  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.

• anastrozole

  anastrozole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aprepitant

  aprepitant will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• armodafinil

  armodafinil will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atazanavir

  atazanavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  budesonide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• butabarbital

  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.

• butalbital

  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.

• carbamazepine

  carbamazepine will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• celecoxib

  bosentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cevimeline

  bosentan will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cimetidine

  cimetidine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• clarithromycin

  bosentan will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• clomipramine

  bosentan will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• conivaptan

  conivaptan will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cornsilk

  cornsilk increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• cortisone

  cortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dapsone

  bosentan will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darifenacin

  darifenacin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darunavir

  darunavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dasatinib

  dasatinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexamethasone

  dexamethasone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• DHEA, herbal

  DHEA, herbal will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diclofenac

  bosentan will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• disopyramide

  bosentan will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• disulfiram

  disulfiram will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• docetaxel

  bosentan will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• donepezil

  bosentan will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dronedarone

  dronedarone will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dutasteride

  bosentan will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• efavirenz

  bosentan will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  efavirenz will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eplerenone

  bosentan will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  esomeprazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• etravirine

  etravirine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  etravirine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  bosentan will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• felbamate

  felbamate will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• finasteride

  bosentan will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluconazole

  fluconazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  fluconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• flurbiprofen

  bosentan will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  bosentan will decrease the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• forskolin

  forskolin increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• fosamprenavir

  fosamprenavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosaprepitant

  fosaprepitant will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosphenytoin

  fosphenytoin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• galantamine

  bosentan will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• grapefruit

  grapefruit will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• griseofulvin

  griseofulvin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydrocortisone

  hydrocortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ibuprofen

  bosentan will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  bosentan will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• imatinib

  bosentan will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• imipramine

  bosentan will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• indinavir

  indinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isradipine

  bosentan will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ketoconazole

  ketoconazole 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 ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lansoprazole

  bosentan will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lapatinib

  lapatinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• leflunomide

  leflunomide will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• levoketoconazole

  levoketoconazole 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 levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lumefantrine

  lumefantrine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• maitake

  maitake increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• meloxicam

  bosentan will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• methylprednisolone

  methylprednisolone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  metronidazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  miconazole vaginal will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• montelukast

  bosentan will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nateglinide

  nateglinide will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nelfinavir

  nelfinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nevirapine

  nevirapine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  nilotinib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nimodipine

  bosentan will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nitrendipine

  bosentan will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• octacosanol

  octacosanol increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• omeprazole

  omeprazole 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 omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ondansetron

  bosentan will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

  bosentan will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel

  bosentan will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  bosentan will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• parecoxib

  bosentan will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pentobarbital

  pentobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  pentobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• phenytoin

  phenytoin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pimozide

  bosentan will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pioglitazone

  bosentan will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• piroxicam

  bosentan will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• posaconazole

  posaconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• prednisone

  prednisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• primidone

  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.

• propafenone

  bosentan will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quinine

  bosentan will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rabeprazole

  bosentan will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  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.

• reishi

  reishi increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• rifapentine

  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.

• ritonavir

  ritonavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rufinamide

  rufinamide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• saxagliptin

  bosentan will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• secobarbital

  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.

• shepherd's purse

  shepherd's purse, bosentan. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sufentanil

  bosentan will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sulfamethoxazole

  sulfamethoxazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ticlopidine

  ticlopidine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tizanidine

  tizanidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tolbutamide

  bosentan will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• topiramate

  topiramate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• treprostinil

  treprostinil increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• valproic acid

  valproic acid will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• verapamil

  verapamil will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinblastine

  bosentan will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine

  bosentan will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  bosentan will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  bosentan will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• voclosporin

  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.

• voriconazole

  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.

• zafirlukast

  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.

• zaleplon

  bosentan will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziprasidone

  bosentan will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zolpidem

  bosentan will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  bosentan will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of bosentan 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.

• abemaciclib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• abiraterone

  Monitor Closely (1)bosentan decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

• acalabrutinib

  Monitor Closely (1)bosentan will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  Minor (1)agrimony increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• aldesleukin

  Monitor Closely (1)aldesleukin increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alfentanil

  Minor (1)bosentan will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

  Minor (1)bosentan will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• almotriptan

  Monitor Closely (1)bosentan will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alosetron

  Minor (2)bosentan will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  bosentan will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alpelisib

  Monitor Closely (1)alpelisib will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)bosentan will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

• alprazolam

  Monitor Closely (1)bosentan will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ambrisentan

  Minor (1)bosentan will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amifostine

  Monitor 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.

• amiodarone

  Monitor 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.

• amitriptyline

  Minor (1)bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amlodipine

  Monitor 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.

• amobarbital

  Minor (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.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Monitor 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.

• apremilast

  Serious - 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 efficacy

• aprepitant

  Monitor 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.

• aripiprazole

  Monitor Closely (1)bosentan will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• armodafinil

  Minor (1)armodafinil will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  Contraindicated (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.

• atazanavir

  Serious - 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.

• atogepant

  Monitor 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.

• atorvastatin

  Monitor Closely (1)bosentan will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avanafil

  Monitor Closely (1)bosentan will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avapritinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• avatrombopag

  Monitor 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.

• axitinib

  Serious - 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 estrogens

  Monitor Closely (1)bosentan will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bedaquiline

  Serious - 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 effect

• belumosudil

  Monitor 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.

• belzutifan

  Monitor 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/acetaminophen

  Monitor 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.

• benzphetamine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of benzphetamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bexarotene

  Monitor Closely (1)bosentan will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bortezomib

  Monitor Closely (1)bosentan will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosutinib

  Serious - 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% .

• brexpiprazole

  Monitor 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.

• brigatinib

  Serious - 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.

• brimonidine

  Minor (1)brimonidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• bromocriptine

  Monitor Closely (1)bosentan will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide

  Monitor 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.

• buprenorphine

  Monitor Closely (1)bosentan will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (1)bosentan will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine subdermal implant

  Monitor 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 transdermal

  Monitor 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 injection

  Monitor 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.

• buspirone

  Monitor Closely (1)bosentan will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  Minor (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.

• butalbital

  Minor (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.

• cabazitaxel

  Monitor 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.

• cabozantinib

  Serious - 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.

• calcifediol

  Monitor 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.

• calcitriol

  Monitor Closely (1)bosentan will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cannabidiol

  Monitor 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.

• capmatinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• carbamazepine

  Monitor 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.

• carbidopa

  Monitor 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.

• cariprazine

  Contraindicated (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.

• carvedilol

  Monitor Closely (1)bosentan will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• celecoxib

  Minor (1)bosentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cenobamate

  Monitor 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.

• ceritinib

  Monitor 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.

• cevimeline

  Minor (1)bosentan will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• chloramphenicol

  Monitor Closely (1)chloramphenicol will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• chlordiazepoxide

  Monitor Closely (1)bosentan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cholic acid

  Monitor 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.

• cilostazol

  Monitor Closely (1)bosentan will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)cimetidine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cinacalcet

  Monitor Closely (1)bosentan will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• citalopram

  Monitor Closely (1)bosentan will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)bosentan will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• clomipramine

  Minor (1)bosentan will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• clonazepam

  Monitor Closely (1)bosentan will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clopidogrel

  Monitor Closely (1)bosentan will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  Monitor Closely (1)bosentan will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clozapine

  Monitor Closely (1)bosentan will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cobicistat

  Monitor Closely (1)bosentan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Bosentan dose reduction required. Refer to the prescribing information of bosentan and cobicistat for recommended dosage adjustments.Serious - Use Alternative (1)cobicistat will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Bosentan dose reduction required

• cobimetinib

  Contraindicated (1)bosentan will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• colchicine

  Monitor Closely (1)bosentan will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)bosentan will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)conivaptan will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• conjugated estrogens

  Monitor Closely (1)bosentan will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (1)bosentan will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• copanlisib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cornsilk

  Minor (1)cornsilk increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• cortisone

  Monitor Closely (1)bosentan will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)cortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Contraindicated (1)cyclosporine will increase the level or effect of bosentan by Other (see comment). Contraindicated. may increase plasma concentrations of OATP substratesSerious - Use Alternative (1)cyclosporine will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)bosentan decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dantrolene

  Monitor Closely (1)bosentan will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dapsone

  Minor (1)bosentan will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• daridorexant

  Serious - Use Alternative (1)bosentan will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  Monitor Closely (1)bosentan will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)darifenacin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darunavir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of darunavir 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)darunavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dasatinib

  Monitor Closely (1)bosentan will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)dasatinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  Serious - Use Alternative (1)bosentan will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• delavirdine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of delavirdine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dexamethasone

  Monitor Closely (1)bosentan will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)dexamethasone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• DHEA, herbal

  Minor (1)DHEA, herbal will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diazepam

  Monitor Closely (1)bosentan will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)bosentan will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.

• diclofenac

  Minor (1)bosentan will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• dienogest/estradiol valerate

  Contraindicated (1)bosentan will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

• dihydroergotamine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)bosentan will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diltiazem

  Monitor Closely (2)diltiazem 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 diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  Minor (1)bosentan will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• docetaxel

  Minor (1)bosentan will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• donepezil

  Minor (1)bosentan will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• doravirine

  Contraindicated (1)bosentan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• doxorubicin

  Monitor Closely (1)bosentan will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxorubicin liposomal

  Monitor Closely (1)bosentan will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dronabinol

  Monitor Closely (2)bosentan will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  bosentan will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)dronedarone will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dutasteride

  Minor (1)bosentan will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• duvelisib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• efavirenz

  Monitor Closely (1)efavirenz will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (2)bosentan will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  efavirenz will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elacestrant

  Serious - Use Alternative (1)bosentan will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (2)bosentan will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  elagolix will decrease the level or effect of bosentan 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.

• elbasvir/grazoprevir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

• eletriptan

  Monitor Closely (1)bosentan will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eliglustat

  Serious - Use Alternative (1)bosentan will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

• elvitegravir

  Monitor Closely (1)elvitegravir, bosentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases bosentan levels, and bosentan decreases elvitegravir levels; if elvitegravir received for >10 days, start bosentan at 62.5 mg/day or every other day; if patient taking bosentan and starting elvitegravir, discontinue bosentan at least 36 hr beforehand, may resume bosentan at 62.5 mg/day or every other day after 10 days.Serious - Use Alternative (1)bosentan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Contraindicated (1)bosentan decreases levels of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May lead to loss of virologic response and possible resistance.Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; dosage modification required for bosentan.

• encorafenib

  Monitor Closely (2)encorafenib, bosentan. 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.
  
  encorafenib will increase the level or effect of bosentan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.Serious - Use Alternative (1)bosentan will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• enzalutamide

  Monitor Closely (2)bosentan will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  enzalutamide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eplerenone

  Minor (1)bosentan will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• erdafitinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP2C9 or CYP3A4 inducers with erdafitinib.

• ergotamine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erlotinib

  Monitor Closely (1)bosentan will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase 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 erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase 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 erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase 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 erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase 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 erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Monitor Closely (2)bosentan will decrease the level or effect of esomeprazole by increasing metabolism. Use Caution/Monitor.
  
  bosentan will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)esomeprazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• estradiol

  Monitor Closely (1)bosentan will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  Monitor Closely (1)bosentan will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)bosentan will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens esterified

  Monitor Closely (1)bosentan will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)bosentan will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eszopiclone

  Monitor Closely (1)bosentan will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethinylestradiol

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

• ethosuximide

  Monitor Closely (1)bosentan will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethotoin

  Monitor Closely (1)bosentan will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etonogestrel

  Monitor Closely (1)bosentan will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etoposide

  Monitor Closely (1)bosentan will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  Monitor Closely (2)bosentan will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  bosentan will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)etravirine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  etravirine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  Minor (1)bosentan will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• everolimus

  Serious - Use Alternative (1)bosentan will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• exemestane

  Monitor Closely (1)bosentan will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.Serious - Use Alternative (1)bosentan will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• felbamate

  Monitor Closely (1)bosentan will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)felbamate will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• felodipine

  Monitor Closely (1)bosentan will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fentanyl

  Monitor Closely (1)bosentan will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl intranasal

  Monitor Closely (1)bosentan will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl transdermal

  Monitor Closely (1)bosentan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fentanyl transmucosal

  Monitor Closely (1)bosentan will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical 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.

• fesoterodine

  Monitor Closely (1)bosentan will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fexinidazole

  Serious - Use Alternative (2)bosentan will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.
  
  fexinidazole will increase the level or effect of bosentan 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.

• finasteride

  Minor (1)bosentan will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• finerenone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)bosentan 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.

• fluconazole

  Minor (2)fluconazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  fluconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (1)bosentan will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)fludrocortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)bosentan will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flurbiprofen

  Minor (1)bosentan will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  Minor (1)bosentan will decrease the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)fluvoxamine will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• forskolin

  Minor (1)forskolin increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• fosamprenavir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of fosamprenavir 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)fosamprenavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosaprepitant

  Monitor Closely (1)bosentan will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)fosaprepitant will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosphenytoin

  Monitor Closely (1)bosentan will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)fosphenytoin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fostamatinib

  Monitor Closely (1)bosentan will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

  Contraindicated (1)bosentan will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.Monitor Closely (1)fostemsavir 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.

• galantamine

  Minor (1)bosentan will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ganaxolone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• gefitinib

  Monitor Closely (1)bosentan 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.

• glasdegib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glecaprevir/pibrentasvir

  Monitor Closely (2)bosentan 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 OATP1B3

• glyburide

  Contraindicated (2)bosentan, glyburide. Either decreases levels of the other by increasing metabolism. Contraindicated.
  
  bosentan, glyburide. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration increases risk of liver enzyme elevations; alternative hypoglycemic agents should be considered.Monitor Closely (1)bosentan decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

• grapefruit

  Minor (1)grapefruit will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)bosentan 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.

• haloperidol

  Monitor Closely (1)bosentan will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (1)bosentan 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 depression

• hydrocortisone

  Monitor Closely (1)bosentan will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)hydrocortisone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydroxyprogesterone caproate (DSC)

  Monitor Closely (1)bosentan will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ibrutinib

  Serious - Use Alternative (1)bosentan decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• ibuprofen

  Minor (1)bosentan will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  Minor (1)bosentan will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• idelalisib

  Serious - Use Alternative (2)bosentan will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure
  
  idelalisib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• ifosfamide

  Monitor Closely (1)bosentan 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.

• iloperidone

  Monitor Closely (2)bosentan 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.

• imatinib

  Monitor Closely (1)imatinib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)bosentan will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• imipramine

  Minor (1)bosentan will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• indinavir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of indinavir 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)indinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• infigratinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  Serious - Use Alternative (1)bosentan will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  Serious - Use Alternative (1)bosentan will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isavuconazonium sulfate

  Contraindicated (1)bosentan will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isoniazid

  Monitor Closely (1)isoniazid will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• isosorbide dinitrate

  Monitor Closely (1)bosentan will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isosorbide mononitrate

  Monitor Closely (1)bosentan will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isradipine

  Minor (1)bosentan will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• istradefylline

  Monitor Closely (1)istradefylline 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.Serious - Use Alternative (1)bosentan will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  Monitor Closely (2)bosentan will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  itraconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ivabradine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

• ivacaftor

  Serious - Use Alternative (1)bosentan decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

• ivosidenib

  Serious - Use Alternative (3)bosentan will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.
  
  ivosidenib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixabepilone

  Monitor Closely (1)bosentan will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ixazomib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• ketoconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)ketoconazole 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 ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lansoprazole

  Minor (1)bosentan will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lapatinib

  Monitor Closely (1)bosentan will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)lapatinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  Monitor Closely (1)larotrectinib will increase 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 larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• lefamulin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• leflunomide

  Minor (1)leflunomide will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lemborexant

  Serious - Use Alternative (1)bosentan will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lenacapavir

  Monitor Closely (1)lenacapavir 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. Serious - Use Alternative (1)bosentan will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  Serious - Use Alternative (2)bosentan will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  leniolisib will increase the level or effect of bosentan by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates

• lesinurad

  Monitor Closely (1)bosentan will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• letermovir

  Monitor Closely (1)letermovir 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.

• levamlodipine

  Monitor Closely (1)bosentan 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.

• levodopa

  Monitor Closely (1)levodopa increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levoketoconazole

  Monitor Closely (1)levoketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)levoketoconazole 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 levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levonorgestrel intrauterine

  Monitor Closely (1)bosentan decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral

  Monitor Closely (1)bosentan decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)bosentan 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.

• linagliptin

  Monitor Closely (1)bosentan 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.

• lofexidine

  Serious - Use Alternative (1)lofexidine, bosentan. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

• lomitapide

  Monitor Closely (1)bosentan will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lonafarnib

  Contraindicated (1)bosentan will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lopinavir

  Monitor Closely (1)bosentan will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)lopinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• loratadine

  Monitor Closely (1)bosentan will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lorlatinib

  Contraindicated (1)bosentan will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.Monitor Closely (1)lorlatinib will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• losartan

  Monitor Closely (2)bosentan 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.

• lovastatin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumacaftor/ivacaftor

  Contraindicated (1)bosentan will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.Monitor Closely (1)lumacaftor/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. .

• lumateperone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumefantrine

  Contraindicated (1)bosentan will decrease the level or effect of 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)lumefantrine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Monitor Closely (1)bosentan 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.

• lurbinectedin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• macitentan

  Serious - 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

• maitake

  Minor (1)maitake increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• maraviroc

  Monitor Closely (1)bosentan will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• marijuana

  Monitor Closely (1)bosentan will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Contraindicated (1)bosentan will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• medroxyprogesterone

  Monitor Closely (1)bosentan 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.

• mefloquine

  Monitor Closely (1)bosentan will decrease the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• meloxicam

  Minor (1)bosentan will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• mestranol

  Monitor Closely (1)bosentan will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methadone

  Monitor Closely (1)bosentan will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methylprednisolone

  Monitor Closely (1)bosentan will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)methylprednisolone will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metronidazole

  Minor (2)metronidazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  metronidazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (2)miconazole vaginal will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  miconazole vaginal will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (1)bosentan will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midostaurin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  Monitor Closely (1)bosentan 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 manufacturerSerious - Use Alternative (1)mifepristone will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mirtazapine

  Monitor Closely (1)bosentan will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane 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.

• mobocertinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• montelukast

  Minor (1)bosentan will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• naldemedine

  Monitor Closely (1)bosentan 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.

• naloxegol

  Contraindicated (1)bosentan will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of naloxegol with strong CYP3A4 inducers is not recommended

• nateglinide

  Monitor Closely (1)bosentan will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)nateglinide will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nefazodone

  Monitor Closely (2)nefazodone 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.

• nelfinavir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of nelfinavir 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)nelfinavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• neratinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• netupitant/palonosetron

  Serious - Use Alternative (1)bosentan will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

• nevirapine

  Monitor Closely (1)bosentan will decrease the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)nevirapine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Monitor Closely (1)bosentan will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)bosentan will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• nilotinib

  Monitor Closely (1)bosentan will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)nilotinib will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nimodipine

  Minor (1)bosentan will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nirmatrelvir

  Serious - Use Alternative (1)nirmatrelvir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of nirmatrelvir/ritonavir for 5 days may result in significant increases bosentan trough concentrations. Discontinue bosentan at least 36 hr before initiating nirmatrelvir/ritonavir. May resume bosentan 10 days after initiating nirmatrelvir/ritonavir.

• nirmatrelvir/ritonavir

  Serious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of nirmatrelvir/ritonavir for 5 days may result in significant increases bosentan trough concentrations. Discontinue bosentan at least 36 hr before initiating nirmatrelvir/ritonavir. May resume bosentan 10 days after initiating nirmatrelvir/ritonavir.

• nisoldipine

  Monitor Closely (1)bosentan will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nitisinone

  Monitor Closely (1)nitisinone 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.

• nitrendipine

  Minor (1)bosentan will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• norethindrone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• norgestrel

  Serious - Use Alternative (1)bosentan will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• octacosanol

  Minor (1)octacosanol increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• olaparib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inducers cannot be avoided, be aware of a potential for decreased efficacy of olaparib

• oliceridine

  Monitor Closely (1)bosentan 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.

• olutasidenib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Contraindicated (1)bosentan will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers may reduce partiaprevir and ritonavir levels, and therefore decreased efficacy of Viekira Pak

• omeprazole

  Minor (2)omeprazole 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 omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ondansetron

  Minor (1)bosentan will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• osilodrostat

  Monitor Closely (1)bosentan 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.

• osimertinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• ospemifene

  Monitor Closely (2)bosentan 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.

• oxcarbazepine

  Minor (1)oxcarbazepine will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

  Minor (1)bosentan will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (1)bosentan decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paclitaxel

  Minor (1)bosentan will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  Minor (1)bosentan will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• palbociclib

  Monitor Closely (1)bosentan will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• panobinostat

  Contraindicated (1)bosentan decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

• parecoxib

  Monitor Closely (1)bosentan will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)bosentan will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paricalcitol

  Monitor Closely (1)bosentan will decrease the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pazopanib

  Monitor Closely (1)bosentan will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (1)peginterferon 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. .

• pemigatinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pentobarbital

  Minor (2)pentobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  pentobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• perampanel

  Serious - Use Alternative (1)bosentan will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenobarbital

  Minor (2)phenobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• phenytoin

  Monitor Closely (1)bosentan will decrease the level or effect of phenytoin by affecting hepatic 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.

• pimavanserin

  Monitor 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.

• pimozide

  Minor (1)bosentan will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pioglitazone

  Minor (1)bosentan will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• piroxicam

  Minor (1)bosentan will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• pitolisant

  Monitor 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 vedotin

  Monitor 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.

• pomalidomide

  Serious - Use Alternative (1)bosentan decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ponatinib

  Serious - 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.

• posaconazole

  Minor (1)posaconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pralsetinib

  Serious - 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.

• praziquantel

  Contraindicated (1)bosentan decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

• prednisolone

  Monitor Closely (1)bosentan will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• prednisone

  Monitor 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.

• pretomanid

  Serious - 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.

• primaquine

  Monitor Closely (1)bosentan will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primidone

  Minor (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 gel

  Serious - 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 micronized

  Serious - 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, natural

  Serious - 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.

• propafenone

  Minor (1)bosentan will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quazepam

  Monitor Closely (1)bosentan will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quetiapine

  Monitor Closely (1)bosentan will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

  Monitor Closely (1)bosentan will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinine

  Minor (1)bosentan will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rabeprazole

  Minor (1)bosentan will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  Minor (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.

• ranolazine

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• regorafenib

  Contraindicated (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.

• reishi

  Minor (1)reishi increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• repaglinide

  Monitor Closely (1)bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ribociclib

  Monitor 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.

• rifabutin

  Monitor 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.

• rifampin

  Monitor 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.

• rifapentine

  Minor (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.

• rimegepant

  Serious - Use Alternative (1)bosentan will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• riociguat

  Monitor 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 adjustment

• ripretinib

  Serious - 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.

• ritonavir

  Serious - 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.

• rivaroxaban

  Monitor Closely (1)bosentan will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• roflumilast

  Contraindicated (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 effectiveness

• romidepsin

  Serious - 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.

• rucaparib

  Monitor 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.

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib

  Monitor Closely (1)bosentan will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib topical

  Monitor Closely (1)bosentan will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• saquinavir

  Monitor 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.

• saxagliptin

  Minor (1)bosentan will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• secobarbital

  Minor (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.

• selpercatinib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  Serious - 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 purse

  Minor (1)shepherd's purse, bosentan. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sildenafil

  Monitor 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 levels

• silodosin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  Serious - 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.

• sirolimus

  Serious - 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/velpatasvir

  Serious - 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.

• solifenacin

  Monitor Closely (1)bosentan will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sonidegib

  Serious - 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.

• sorafenib

  Monitor Closely (1)bosentan decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• sotorasib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sparsentan

  Contraindicated (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 Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• stiripentol

  Monitor 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.

• sufentanil

  Minor (1)bosentan will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sufentanil SL

  Monitor 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.

• sulfamethoxazole

  Minor (1)sulfamethoxazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sunitinib

  Monitor Closely (1)bosentan will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  Monitor 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/day

• tacrolimus

  Monitor Closely (1)bosentan will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  Monitor Closely (1)bosentan will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tamoxifen

  Monitor 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.

• tamsulosin

  Monitor Closely (1)bosentan will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tasimelteon

  Monitor 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 inducers

• tazemetostat

  Monitor 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.

• tecovirimat

  Monitor 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.

• temsirolimus

  Monitor Closely (1)bosentan will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tenapanor

  Monitor 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.

• teniposide

  Monitor Closely (1)bosentan will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbinafine

  Monitor 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.

• tetracycline

  Monitor Closely (1)bosentan will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tezacaftor

  Serious - Use Alternative (1)bosentan will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• theophylline

  Monitor Closely (1)bosentan will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tiagabine

  Monitor Closely (1)bosentan will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ticagrelor

  Monitor 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.

• ticlopidine

  Monitor 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.

• tinidazole

  Monitor Closely (1)bosentan will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Monitor 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.

• tivozanib

  Serious - Use Alternative (1)bosentan will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tizanidine

  Minor (1)tizanidine increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tofacitinib

  Monitor 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 inducers

• tolbutamide

  Minor (1)bosentan will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (1)bosentan will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  Serious - Use Alternative (1)bosentan will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• topiramate

  Minor (1)topiramate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• toremifene

  Monitor 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.

• trabectedin

  Serious - Use Alternative (1)bosentan will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tramadol

  Monitor 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 inducers

• trazodone

  Serious - Use Alternative (1)bosentan will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• treprostinil

  Minor (1)treprostinil increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)bosentan will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  Monitor Closely (1)bosentan will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trofinetide

  Serious - 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.

• tucatinib

  Serious - 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.

• ubrogepant

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  Serious - 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.

• valbenazine

  Monitor Closely (1)bosentan will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• valproic acid

  Minor (1)valproic acid will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• vandetanib

  Contraindicated (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%.

• vardenafil

  Monitor Closely (1)bosentan will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• velpatasvir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vemurafenib

  Monitor Closely (1)bosentan will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• venetoclax

  Serious - 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.

• verapamil

  Monitor 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.

• vilazodone

  Monitor 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.

• vinblastine

  Minor (1)bosentan will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine

  Minor (1)bosentan will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  Minor (1)bosentan will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  Minor (1)bosentan will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• voclosporin

  Serious - 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.

• vonoprazan

  Serious - Use Alternative (1)bosentan will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vorapaxar

  Serious - Use Alternative (1)bosentan decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Monitor 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.

• vortioxetine

  Monitor 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.

• voxelotor

  Serious - 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.

• voxilaprevir

  Serious - Use Alternative (1)bosentan will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• warfarin

  Monitor Closely (1)bosentan will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• xipamide

  Monitor Closely (1)xipamide increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor.

• zafirlukast

  Minor (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.

• zaleplon

  Minor (1)bosentan will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zanubrutinib

  Serious - 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.

• ziprasidone

  Minor (1)bosentan will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zolpidem

  Minor (1)bosentan will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  Minor (1)bosentan will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.