Bosentan: Drug information

(For additional information see "Bosentan: Patient drug information" and see "Bosentan: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Distribution program:

Because of the risks of hepatotoxicity and birth defects, bosentan is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program.

Hepatotoxicity:

In clinical studies, bosentan caused at least a 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (more than 12 months) therapy with bosentan in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure. The contribution of bosentan in these cases could not be excluded.

In at least 1 case, the initial presentation of hepatotoxicity (after more than 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by nonspecific symptoms, all of which resolved slowly over time after discontinuation of bosentan. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping bosentan if a rise of aminotransferase accompanied by signs or symptoms of liver dysfunction occurs.

Elevations in aminotransferases require close attention. Generally, avoid using bosentan in patients with elevated aminotransferases (greater than 3 times the ULN) at baseline because monitoring for hepatotoxicity may be more difficult. Stop treatment with bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (eg, abdominal pain, fever, jaundice, nausea, unusual lethargy or fatigue, vomiting) or increases in bilirubin 2 times the ULN or greater. There is no experience with the reintroduction of bosentan in these circumstances.

Embryo-fetal toxicity:

Bosentan is likely to cause major birth defects if used by pregnant women based on animal data. Therefore, pregnancy must be excluded before the start of treatment with bosentan. Throughout treatment and for 1 month after stopping bosentan, women of childbearing potential must use 2 reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives, should not be used as the sole means of contraception because these may not be effective in patients receiving bosentan. Obtain monthly pregnancy tests.

Brand Names: US

Tracleer

Brand Names: Canada

APO-Bosentan [DSC];
BIO-Bosentan [DSC];
NAT-Bosentan;
PMS-Bosentan;
SANDOZ Bosentan [DSC];
TARO-Bosentan;
TEVA-Bosentan [DSC];
Tracleer

Pharmacologic Category

Endothelin Receptor Antagonist;
Vasodilator

Dosing: Adult

Pulmonary arterial hypertension

Pulmonary arterial hypertension:

Note: Consult a pulmonary arterial hypertension specialist for all management decisions; choice of therapy is dependent on etiology, risk stratification, and cardiopulmonary comorbidities (Ref).

<40 kg: Oral: Initial and maintenance: 62.5 mg twice daily.

≥40 kg: Oral: Initial: 62.5 mg twice daily; after ~4 weeks, may increase to a maximum dose of 125 mg twice daily.

Note: When discontinuing treatment, consider a reduction in dosage to 62.5 mg twice daily for 3 to 7 days to avoid clinical deterioration, then stop treatment.

Digital ulcers in systemic sclerosis

Digital ulcers in systemic sclerosis (off-label use): Oral: 62.5 mg twice daily for 4 weeks followed by an increase to a maintenance dose of 125 mg twice daily (Ref).

Raynaud phenomenon in systemic sclerosis

Raynaud phenomenon in systemic sclerosis (off-label use): Oral: 62.5 mg twice daily for 4 weeks followed by an increase to a maintenance dose of 125 mg twice daily (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary. Bosentan is unlikely to be removed by dialysis (due to high molecular weight and extensive plasma protein binding).

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation:

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate to severe impairment (Child-Pugh class B and C) and/or baseline transaminase >3 times ULN: Avoid use; systemic exposure is significantly increased in patients with moderate impairment (has not been studied in severe impairment).

Hepatotoxicity during treatment: Modification based on transaminase elevation:

Transaminase elevations accompanied by clinical symptoms of hepatotoxicity (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin ≥2 times ULN: Discontinue treatment.

AST/ALT >3 times but ≤5 times ULN: >40 kg: Confirm with additional test; if confirmed, reduce dose to 62.5 mg twice daily or interrupt treatment and monitor at least every 2 weeks. If transaminase levels return to pretreatment values, may continue or reintroduce treatment (at the starting dose), as appropriate. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

AST/ALT >5 times but ≤8 times ULN: >40 kg: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels at least every 2 weeks. If transaminase levels return to pretreatment values, may reintroduce treatment (at the starting dose) as appropriate. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

AST/ALT >8 times ULN: Stop treatment and do not reintroduce.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Bosentan: Pediatric drug information")

Pulmonary arterial hypertension

Pulmonary arterial hypertension: Note: Doses >125 mg twice daily do not provide additional benefit sufficient to offset the increased risk of hepatic injury.

Infants and Children <12 years: Oral: Initial: 1 mg/kg/dose twice daily; increase to a target dose of 2 mg/kg/dose twice daily; maximum dose: 125 mg/dose (Ref).

Children ≥12 years and Adolescents (Ref): Oral:

>20 to 40 kg: Initial: 31.25 mg twice daily; increase to a target dose of 62.5 mg twice daily.

>40 kg: Initial: 62.5 mg twice daily; increase to a target dose of 125 mg twice daily.

Alternate dosing: Manufacturer's labeling:

Children ≥3 years:

4 to 8 kg: Oral: 16 mg twice daily.

>8 to 16 kg: Oral: 32 mg twice daily.

>16 to 24 kg: Oral: 48 mg twice daily.

>24 to 40 kg: Oral: 64 mg twice daily.

Adolescents:

≤40 kg: Oral: 62.5 mg twice daily.

>40 kg: Oral: Initial: 62.5 mg twice daily for 4 weeks; increase to target dose of 125 mg twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

No dosage adjustment required. Bosentan is unlikely to be removed by dialysis (due to high molecular weight and extensive plasma protein binding).

Dosing: Hepatic Impairment: Pediatric

Baseline: Children ≥3 years and Adolescents:

Mild impairment: No dosage adjustment necessary.

Moderate to severe impairment and/or baseline transaminase >3 times ULN: Avoid use; systemic exposure is significantly increased in patients with moderate impairment (has not been studied in severe impairment).

Hepatotoxicity during therapy: Adjustment based on transaminase elevation:

AST/ALT >3 times but ≤5 times ULN:

Children 3 to ≤12 years and Adolescents ≤40 kg: Confirm with additional test; if confirmed, interrupt treatment with no prior dose reduction. If transaminase levels return to pretreatment values, may reintroduce treatment at the dose used prior to treatment interruption. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

Adolescents >40 kg: Confirm with additional test; if confirmed, reduce dose to 62.5 mg twice daily or interrupt treatment and monitor at least every 2 weeks. If transaminase levels return to pretreatment values, may continue or reintroduce treatment at 62.5 mg twice daily, as appropriate. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

AST/ALT >5 times but ≤8 times ULN:

Children 3 to ≤12 years and Adolescents ≤40 kg: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels at least every 2 weeks. If transaminase levels return to pretreatment values, consider reintroduction at the dose used prior to treatment interruption. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

Adolescents >40 kg: Confirm with additional test; if confirmed, stop treatment. Monitor transaminase levels at least every 2 weeks. If transaminase levels return to pretreatment values, may reintroduce treatment at 62.5 mg twice daily, as appropriate. When reintroducing treatment, recheck transaminases within 3 days and at least every 2 weeks thereafter.

AST/ALT >8 times ULN: Children ≥3 years and Adolescents: Stop treatment and do not reintroduce.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Edema (≤11%)

Central nervous system: Headache (15%)

Hepatic: Increased serum ALT (≥3 times ULN: ≤12%; 8 times ULN: ≤2%; dose-related), increased serum AST (≥3 times ULN: ≤12%; 8 times ULN: ≤2%; dose-related)

Respiratory: Respiratory tract infection (22%)

1% to 10%:

Cardiovascular: Chest pain (5%), syncope (5%), flushing (4%), hypotension (4%), palpitations (4%)

Endocrine & metabolic: Fluid retention (≤2%)

Hematologic & oncologic: Anemia (3%)

Neuromuscular & skeletal: Arthralgia (4%)

Respiratory: Sinusitis (4%)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, DRESS syndrome, hepatic cirrhosis (prolonged therapy), hepatic failure (rare), hypersensitivity reaction, jaundice, leukopenia, nasal congestion, neutropenia, peripheral edema, severe anemia, skin rash, thrombocytopenia

Contraindications

Hypersensitivity to bosentan or any component of the formulation; concurrent use of cyclosporine or glyburide; women who are or may become pregnant.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Moderate to severe hepatic impairment (eg, ALT or AST >3 times ULN, particularly when total bilirubin >2 times ULN).

Warnings/Precautions

Concerns related to adverse effects:

• Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur. There have also been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization) for heart failure. If clinically significant fluid retention develops (with or without weight gain), further evaluation is necessary to determine cause and appropriate treatment or discontinuation of therapy. Use with caution in patients with underlying heart failure due to potential complications from fluid retention. In a scientific statement from the American Heart Association, bosentan has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hematologic effects: Dose-related decreases in hematocrit/hemoglobin may be observed, usually within the first few weeks of therapy with subsequent stabilization of levels by 4 to 12 weeks of treatment. Monitor hemoglobin prior to treatment initiation, after 1 and 3 months, and every 3 months thereafter. Significant decreases in hemoglobin require further evaluation to determine the cause and specific management.

• Hepatotoxicity: [US Boxed Warning]: Bosentan is associated with transaminase elevations (ALT or AST ≥3 times ULN), and in a small number of cases may occur with elevations in bilirubin. Monitor transaminases at baseline then monthly thereafter. Adjust dosage if elevations in liver enzymes occur without symptoms of hepatic injury or elevated bilirubin. In the postmarketing surveillance (with close monitoring), there have been rare cases of unexplained hepatic cirrhosis after prolonged therapy (>12 months) in patients with multiple comorbidities and drug therapies. There have also been cases of hepatic failure. Treatment should be stopped in patients who develop elevated transaminases either in combination with symptoms of hepatic injury (unusual fatigue, jaundice, nausea, vomiting, abdominal pain, and/or fever) or elevated bilirubin (≥2 times ULN); safety of reintroduction is unknown. Avoid use in patients with baseline serum transaminases >3 times ULN at baseline (monitoring for hepatotoxicity may be more difficult) or moderate to severe hepatic impairment. The combination of hepatocellular injury (transaminase elevations >3 times ULN) and bilirubin increased ≥2 times ULN are a marker for potential serious hepatotoxicity. Transaminase elevations are dose dependent, generally asymptomatic, occur both early and late in therapy, progress slowly, and are usually reversible after treatment interruption or discontinuation. Transaminase elevations may also spontaneously reverse while continuing bosentan treatment. Consider the benefits of treatment versus the risk of hepatotoxicity when initiating therapy in patients with WHO Class II symptoms.

• Hypersensitivity: Hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, rash and angioedema have been observed.

• Pulmonary veno-occlusive disease: If signs of pulmonary edema occur, consider possibility of pulmonary veno-occlusive disease; may require discontinuation of bosentan.

Special populations:

• Pregnancy: [US Boxed Warning]: Bosentan is likely to cause major birth defects if used by pregnant women based on animal data. Therefore, pregnancy must be excluded before the start of treatment with bosentan. Throughout treatment and for 1 month after stopping bosentan, women of childbearing potential must use 2 reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives, should not be used as the sole means of contraception because these may not be effective in patients receiving bosentan. Obtain monthly pregnancy tests.

Dosage form specific issues:

• Aspartame: Some products may contain aspartame, which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.

Other warnings/precautions:

• REMS program: [US Boxed Warning]: Because of the risks of hepatotoxicity and birth defects, bosentan is only available through the Bosentan REMS Program. Patients, prescribers, and pharmacies must enroll with the program. Call 1-866-359-2612 or visit www.BosentanREMSProgram.com for more information.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tracleer: 62.5 mg, 125 mg

Generic: 62.5 mg, 125 mg

Tablet Soluble, Oral:

Tracleer: 32 mg [scored; contains aspartame]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Tablet,Dispersible (Tracleer Oral)

32 mg (per each): $244.03

Tablets (Bosentan Oral)

62.5 mg (per each): $209.14 - $221.00

125 mg (per each): $209.14 - $221.00

Tablets (Tracleer Oral)

62.5 mg (per each): $244.03

125 mg (per each): $244.03

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tracleer: 62.5 mg, 125 mg [contains corn starch]

Generic: 62.5 mg, 125 mg

Administration: Adult

Administer with or without food.

Tablets for oral suspension (dispersible tablets): Disperse in a minimal amount of water immediately before administration. The 32 mg dispersible tablet may be divided into halves; do not break into quarters.

Administration: Pediatric

Note: Bosentan has been classified as a hazardous substance by NIOSH due to its associated risk of birth defects; double gloving, a protective gown, and preparation in a controlled device is recommended when splitting, crushing, or handling broken tablets; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration or handling of bodily fluids/waste (Ref).

Oral: May be administered without regard to meals.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021290s039,209279s005lbl.pdf#page=30, must be dispensed with this medication.

Use: Labeled Indications

Pulmonary arterial hypertension: Treatment of pulmonary artery hypertension (PAH) (WHO Group I) in adults with WHO-FC II, III, or IV symptoms to improve exercise ability and to decrease clinical deterioration; treatment of PAH (WHO Group 1) in pediatric patients ≥3 years with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), resulting in an improvement in exercise ability.

Use: Off-Label: Adult

Digital ulcers in systemic sclerosis; Raynaud phenomenon in systemic sclerosis

Medication Safety Issues

Sound-alike/look-alike issues:

Tracleer may be confused with TriCor

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2C9 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C9 (weak), CYP3A4 (moderate)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Risk C: Monitor therapy

Adagrasib: May increase the serum concentration of Bosentan. Risk X: Avoid combination

ALfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy

AmLODIPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Risk C: Monitor therapy

Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination

Atazanavir: Bosentan may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Bosentan. Management: Concurrent use of unboosted atazanavir (without ritonavir or cobicistat) and bosentan is not recommended. Bosentan dose adjustments and increased monitoring are recommended when used together with boosted atazanavir. See interaction monograph for details. Risk D: Consider therapy modification

Atogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification

Atorvastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy

Avacopan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avacopan. Risk X: Avoid combination

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Risk X: Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Risk X: Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

Belumosudil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Belumosudil. Risk C: Monitor therapy

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Risk C: Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Risk C: Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Risk C: Monitor therapy

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider therapy modification

Buprenorphine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy

BusPIRone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of BusPIRone. Risk C: Monitor therapy

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy

Cannabis: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

Capivasertib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination

CarBAMazepine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Cariprazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination

Ceritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ceritinib. Risk C: Monitor therapy

Clarithromycin: Bosentan may increase serum concentrations of the active metabolite(s) of Clarithromycin. Specifically, bosentan may increase concentrations of 14-hydroxyclarithromycin. Bosentan may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Bosentan. Management: Consider alternative antimicrobial if possible. The clinical activity of clarithromycin may be altered, and increased bosentan toxicity may be expected. Risk D: Consider therapy modification

Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy

Cobicistat: May increase the serum concentration of Bosentan. Management: Dose adjustment of bosentan and increased monitoring for bosentan toxicities is necessary when these agents are combined. See full drug interaction monograph for details. Risk D: Consider therapy modification

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Risk X: Avoid combination

Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Risk C: Monitor therapy

Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Risk C: Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of CycloSPORINE (Systemic). Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Bosentan. Risk C: Monitor therapy

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider therapy modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy

Daridorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination

Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Risk X: Avoid combination

Dasatinib: CYP3A4 Inducers (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination

Delavirdine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Delavirdine. Risk C: Monitor therapy

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy

DiazePAM: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy

Dienogest: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy

DilTIAZem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy

Disopyramide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy

Doravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Doravirine. Risk C: Monitor therapy

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DroNABinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy

Dronedarone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dronedarone. Risk C: Monitor therapy

Duvelisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider therapy modification

Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy

Efavirenz: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Efavirenz. Risk C: Monitor therapy

Elacestrant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination

Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy

Eliglustat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Eliglustat. Risk C: Monitor therapy

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Elvitegravir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elvitegravir. Risk C: Monitor therapy

Encorafenib: May increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of Encorafenib. Risk C: Monitor therapy

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Risk X: Avoid combination

Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Enzalutamide. Risk C: Monitor therapy

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Risk D: Consider therapy modification

Erlotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erlotinib. Risk C: Monitor therapy

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Etravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etravirine. Risk C: Monitor therapy

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Risk C: Monitor therapy

Exemestane: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Exemestane. Risk C: Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Risk X: Avoid combination

Felodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Felodipine. Risk C: Monitor therapy

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Risk C: Monitor therapy

Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination

Finerenone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Finerenone. Risk X: Avoid combination

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination

Fluconazole: May increase the serum concentration of Bosentan. Risk X: Avoid combination

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor therapy

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk C: Monitor therapy

Fostamatinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider therapy modification

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider therapy modification

Gefitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gefitinib. Risk C: Monitor therapy

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: Monitor therapy

Gepirone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gepirone. Risk C: Monitor therapy

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

GlyBURIDE: May enhance the hepatotoxic effect of Bosentan. GlyBURIDE may decrease the serum concentration of Bosentan. Bosentan may decrease the serum concentration of GlyBURIDE. Risk X: Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider therapy modification

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy

Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Risk C: Monitor therapy

Idelalisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Idelalisib. Risk C: Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Imatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Imatinib. Risk C: Monitor therapy

Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy

Isradipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Risk C: Monitor therapy

Itraconazole: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy

Ivabradine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixabepilone. Risk C: Monitor therapy

Ixazomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixazomib. Risk C: Monitor therapy

Ketamine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy

Ketoconazole (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider therapy modification

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification

Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination

Lenacapavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination

Leniolisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination

Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy

Letermovir: Bosentan may decrease the serum concentration of Letermovir. Risk X: Avoid combination

Levamlodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy

Levoketoconazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levoketoconazole. Risk C: Monitor therapy

Levomethadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy

LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of LinaGLIPtin. Risk C: Monitor therapy

Lonafarnib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider therapy modification

Lovastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lovastatin. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Risk D: Consider therapy modification

Macimorelin: Bosentan may diminish the diagnostic effect of Macimorelin. Risk C: Monitor therapy

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Risk C: Monitor therapy

Maraviroc: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider therapy modification

Maribavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Maribavir. Risk C: Monitor therapy

Mavacamten: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination

Mefloquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy

Meperidine: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy

Methadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Methadone. Risk C: Monitor therapy

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy

Mianserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mianserin. Risk C: Monitor therapy

Midazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy

Midostaurin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midostaurin. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of Bosentan. Risk X: Avoid combination

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Risk C: Monitor therapy

Mitapivat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mitapivat. Management: Consider alternatives to this combination when possible. If combined, monitor hemoglobin and titrate mitapivat beyond 50 mg twice daily, if needed, but do not exceed doses of 100 mg twice daily. Risk D: Consider therapy modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Risk C: Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Risk X: Avoid combination

Netupitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Netupitant. Risk C: Monitor therapy

Nevirapine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nevirapine. Risk C: Monitor therapy

NIFEdipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NIFEdipine. Risk C: Monitor therapy

Nilotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilotinib. Risk C: Monitor therapy

Nilvadipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: May increase the serum concentration of Bosentan. Management: Consider alternative COVID-19 treatments in patients taking bosentan. If nirmatrelvir and ritonavir must be used, discontinue bosentan at least 36 hours before initiation of nirmatrelvir and ritonavir. Monitor for increased bosentan toxicities. Risk D: Consider therapy modification

Nirogacestat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Risk X: Avoid combination

Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy

Olutasidenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination

Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination

Orelabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination

Osimertinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Osimertinib. Risk C: Monitor therapy

OxyCODONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

Pacritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Risk C: Monitor therapy

Palovarotene: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Risk C: Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider therapy modification

Phosphodiesterase 5 Inhibitors: Bosentan may decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan. Risk C: Monitor therapy

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Risk X: Avoid combination

Piperaquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Piperaquine. Risk C: Monitor therapy

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider therapy modification

PONATinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PONATinib. Risk C: Monitor therapy

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider therapy modification

Praziquantel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider therapy modification

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy

PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination

Protease Inhibitors: May increase the serum concentration of Bosentan. Management: Dose adjustment of bosentan and increased monitoring for bosentan toxicities is necessary when these agents are combined. See full drug interaction monograph for details. Risk D: Consider therapy modification

QUEtiapine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QUEtiapine. Risk C: Monitor therapy

QuiNIDine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy

QuiNINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNINE. Risk C: Monitor therapy

Quizartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Quizartinib. Risk X: Avoid combination

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination

Regorafenib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy

Repaglinide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy

Repotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination

Ribociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ribociclib. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Bosentan. Following the initial week of concurrent rifampin, this effect is most likely. RifAMPin may increase the serum concentration of Bosentan. This effect is most likely to be observed within the initial few days of concurrent therapy (and may be greatest immediately following initiation of the combination). Risk C: Monitor therapy

Rilpivirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rilpivirine. Risk C: Monitor therapy

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination

Ripretinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider therapy modification

RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy

Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ritlecitinib. Risk C: Monitor therapy

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Risk C: Monitor therapy

Samidorphan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Samidorphan. Risk C: Monitor therapy

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination

Sertraline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy

Sildenafil: Bosentan may decrease the serum concentration of Sildenafil. Sildenafil may increase the serum concentration of Bosentan. Management: When sildenafil is used for treatment of pulmonary arterial hypertension (PAH), coadministration of sildenafil and bosentan is not recommended. Otherwise, monitor for reduced sildenafil efficacy if combined with bosentan. Risk D: Consider therapy modification

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination

Simvastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination

SORAfenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SORAfenib. Risk C: Monitor therapy

Sotorasib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sotorasib. Risk C: Monitor therapy

Sparsentan: May enhance the adverse/toxic effect of Endothelin Receptor Antagonists. Risk X: Avoid combination

SUFentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUFentanil. Risk C: Monitor therapy

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Risk C: Monitor therapy

Suvorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Suvorexant. Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tadalafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tadalafil. Risk C: Monitor therapy

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tamoxifen. Risk C: Monitor therapy

Tasimelteon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination

Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor therapy

Thiotepa: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy

Tivozanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tivozanib. Risk C: Monitor therapy

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Risk C: Monitor therapy

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Risk C: Monitor therapy

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Risk C: Monitor therapy

Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Risk C: Monitor therapy

TraMADol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy

TraZODone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraZODone. Risk C: Monitor therapy

Triazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Triazolam. Risk C: Monitor therapy

Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification

Tucatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tucatinib. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider therapy modification

Ulipristal: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Risk C: Monitor therapy

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy

Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Risk X: Avoid combination

Verapamil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Verapamil. Risk C: Monitor therapy

Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Bosentan may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Voclosporin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination

Vonoprazan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination

Voriconazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voriconazole. Risk C: Monitor therapy

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Risk C: Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxilaprevir. Risk X: Avoid combination

Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Risk C: Monitor therapy

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider therapy modification

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Risk C: Monitor therapy

Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

Zuranolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination

Food Interactions

Bioavailability of bosentan is not affected by food.

Reproductive Considerations

Bosentan is contraindicated in females who may become pregnant.

[US Boxed Warning]: Pregnancy must be excluded before the start of treatment with bosentan. Throughout treatment and for 1 month after stopping bosentan, women of childbearing potential must use two reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives, should not be used as the sole means of contraception because these may not be effective in patients receiving bosentan. Obtain monthly pregnancy tests. When a hormonal or barrier contraceptive is used, one additional method of contraception is still needed if a male partner has had a vasectomy. A missed menses or suspected pregnancy should be reported to a health care provider and prompt immediate pregnancy testing.

Decreased sperm counts and adverse effects on spermatogenesis have been observed in men during treatment; fertility may be impaired. It is not known if effects on fertility are reversible.

Pregnancy Considerations

Bosentan is contraindicated in females who are pregnant.

[US Boxed Warning]: Bosentan is likely to cause major birth defects if used by pregnant women based on animal data.

Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009; Taichman 2014).

Breastfeeding Considerations

It is not known if bosentan is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

Serum transaminase (AST and ALT) and bilirubin (prior to treatment initiation and monthly thereafter, or more frequently if clinically necessary [every 2 weeks following transaminase elevations and 3 days after reintroducing therapy if withheld due to transaminase elevations]). Hemoglobin and hematocrit (at baseline, at 1 month and 3 months of treatment, and every 3 months thereafter [generally stabilizes after 4 to 12 weeks of treatment]).

Pregnancy test in women of childbearing potential (prior to the initiation of therapy, monthly during treatment, and one month after stopping bosentan).

Monitor for clinical signs/symptoms of liver injury (eg, abdominal pain, fatigue, fever, jaundice, nausea, vomiting) and fluid retention.

Mechanism of Action

Endothelin receptor antagonist that blocks endothelin receptors on endothelium and vascular smooth muscle (stimulation of these receptors is associated with vasoconstriction). Bosentan blocks both ET_A and ET_B receptors, with a slightly higher affinity for the A subtype.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: ~18 L (does not distribute into RBCs)

Protein binding, plasma: >98%, primarily to albumin

Metabolism: Hepatic via CYP2C9 and 3A4 to three metabolites (one active, contributing ~10% to 20% pharmacologic activity); steady-state plasma concentrations are 50% to 65% of those attained after single dose (most likely due to autoinduction of liver enzymes); steady-state is attained within 3 to 5 days

Bioavailability: ~50%

Half-life elimination: ~5 hours; prolonged with heart failure, possibly in PAH

Time to peak, plasma: 3 to 5 hours

Excretion: Feces (as metabolites); urine (<3% as unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: In patients with severe renal impairment (CrCl 15 to 30 mL/minute), concentrations of the 3 metabolites may increase 2-fold, although it is not clinically significant.

Hepatic function impairment: Exposure to bosentan may be significantly increased in hepatic impairment.

Pediatric: Exposure to bosentan reaches a plateau at lower doses in pediatric patients than in adults, and doses >2 mg/kg twice daily do not increase the exposure to bosentan in pediatric patients.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Bosentor | Ecole | Tracleer;
(AR) Argentina: Amalox | Bosentac | Bosental | Endotan | Hasnub | Letib | Masican | Talosin | Tracleer | Trasentan | Usenta;
(AT) Austria: Bosentan accord | Bosentan dr reddys | Stayveer | Tracleer;
(AU) Australia: Bosentan apotex | Bosentan cipla | Bosentan dr reddys | Bosentan gh | Bosentan mylan | Bosentan rbx | Bosentan sandoz | Bosleer | Tracleer;
(BD) Bangladesh: Pulmoten;
(BE) Belgium: Bosentan ab | Bosentan accord | Bosentan sandoz | Bosentan teva | Tracleer;
(BG) Bulgaria: Bosentan accord | Ipertazin | Stayveer | Tracleer;
(BR) Brazil: Bosentana | Hagivan | Tracleer;
(CH) Switzerland: Bosentan mepha | Tracleer;
(CL) Chile: Babyx | Tracleer | Usenta;
(CN) China: Tracleer;
(CO) Colombia: Bioxentan | Bolyston | Bontelin | Bosentas | Filipika | Monotan | Paglix | Pulmonell | Purosentan | Safebo | Sulmida | Tabosen | Tensiopril | Tracleer | Usenta;
(CZ) Czech Republic: Bosentan abdi | Bosentan accord | Bosentan avmc | Bosentan ebewe | Bosentan mylan | Bosentan pharmascience international | Bosentan sandoz | Bosentan welding | Stayveer | Tracleer;
(DE) Germany: Bosentan 1a pharma | Bosentan accord | Bosentan aliud | Bosentan basics | Bosentan beta | Bosentan cipla | Bosentan Heumann | Bosentan hexal | Bosentan mylan | Bosentan puren | Bosentan ratiopharm | Bosentan teva | Bosentan zentiva | Tracleer;
(EC) Ecuador: Endotan | Tracleer | Usenta;
(EE) Estonia: Bosentan accord | Bosentan Norameda | Tracleer;
(EG) Egypt: Bosentadin;
(ES) Spain: Bosentan accord | Bosentan aurovitas | Bosentan cipla | Bosentan dr reddys | Bosentan kern pharma | Bosentan mylan | Bosentan normon | Bosentan sandoz | Bosentan sun | Bosentan teva | Stayveer | Tracleer;
(ET) Ethiopia: Bosentan msn;
(FI) Finland: Bosentan accord | Bosentan actavis | Bosentan orion | Stayveer | Tracleer;
(FR) France: Bosentan accord | Bosentan arrow | Bosentan biogaran | Bosentan eg | Bosentan mylan | Bosentan ohre pharma | Bosentan teva | Tracleer;
(GB) United Kingdom: Bosentan | Bosentan accord | Bosentan cipla | Stayveer | Tracleer;
(GR) Greece: Bosentan mylan | Klimurtan | Sentoba | Stayveer | Tracleer | Vradem;
(HK) Hong Kong: Pulmonat | Tracleer;
(HR) Croatia: Phan | Tracleer;
(HU) Hungary: Ipertazin | Stayveer | Trocordis;
(IE) Ireland: Tracleer;
(IL) Israel: Tracleer;
(IN) India: Bosenat | Bosentas | Bozetan | Lupibose | Pulvance;
(IQ) Iraq: Bosentan;
(IT) Italy: Bosentan accord | Bosentan aurobindo | Bosentan doc generici | Bosentan Medac | Bosentan mylan | Bosentan sandoz | Bosentan sun | Bosentan teva | Bosentan zentiva | Tracleer;
(JO) Jordan: Tracleer;
(JP) Japan: Bosentan dsep | Bosentan jg | Bosentan kn | Bosentan mochida | Bosentan pfizer | Bosentan sawai | Bosentan tanabe | Tracleer;
(KE) Kenya: Bosetan | Pulmofirst;
(KR) Korea, Republic of: Canabosen | Pahsentan | Trasista;
(KW) Kuwait: Tracleer;
(LB) Lebanon: Pms bosentan | Tracleer;
(LT) Lithuania: Bosentan accord | Bosentan cipla | Bosentan Norameda | Bosentan sandoz | Tracleer;
(LV) Latvia: Bosentan Norameda | Bosentan sandoz | Tracleer;
(MX) Mexico: Gozzen | Lunastra | Sensord | Tracleer | Zuxtana;
(MY) Malaysia: Bosentas | Proart;
(NL) Netherlands: Bosentan accord | Bosentan aurobindo | Bosentan sandoz | Stayveer | Tracleer;
(NO) Norway: Bosentan accord | Bosentan aurobindo | Bosentan cipla | Bosentan sandoz | Stayveer | Tracleer;
(NZ) New Zealand: Bosentan dr reddys | Mylan bosentan | Tracleer;
(PE) Peru: Canabosen | Pulmofirst | Tracleer | Usenta;
(PK) Pakistan: Bosecard | Bosent | Bosentan | Bosmon | Bosotec | Bozpah | Bsantan;
(PL) Poland: Bopaho | Bosentan celon | Bosentan sandoz | Stayveer | Tracleer;
(PR) Puerto Rico: Tracleer;
(PT) Portugal: Bosentano Accord | Bosentano aurobindo | Bosentano mylan | Bosentano sandoz | Bosentano teva | Bosentano zentiva | Tracleer;
(PY) Paraguay: Bosentan Imedic | Bosentan prosalud | Bosentan vmg | Usenta;
(QA) Qatar: Gonista | Tracleer;
(RO) Romania: Bopaho | Bosentan terapia | Bosentan zentiva | Stayveer | Tracleer;
(RU) Russian Federation: Bosenex | Bosentan | Bozentan canon | Tracleer | Tracleer dt | Vasenex;
(SA) Saudi Arabia: Bosentor | Pms bosentan | Tracleer;
(SE) Sweden: Bosentan accord | Bosentan actavis | Bosentan aurobindo | Bosentan sandoz | Stayveer | Tracleer;
(SI) Slovenia: Bopaho | Bosentan Norameda | Stayveer | Tracleer;
(SK) Slovakia: Bosentan accord | Bosentan mylan | Bosentan sandoz | Stayveer | Tracleer;
(TH) Thailand: Silkay | Tracleer;
(TN) Tunisia: Pms bosentan | Tracleer;
(TR) Turkey: Diamond | Tracleer | Tractan | Zepahex;
(TW) Taiwan: Tracleer;
(UA) Ukraine: Bosentan accord | Bosentan sandoz;
(UG) Uganda: Pulmofirst;
(UY) Uruguay: C.B.A.;
(VN) Viet Nam: Agbosen | Trasenib

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Bosentan: Drug information