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Bosentan: Drug information

Bosentan: Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Bosentan: Patient drug information" and "Bosentan: Pediatric drug information"

For abbreviations, symbols, and age group definitions 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;
  • 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: Liver 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: Liver 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:

Transaminase elevations accompanied by clinical symptoms of hepatotoxicity (unusual fatigue, nausea, vomiting, abdominal pain, fever, or jaundice) or a serum bilirubin ≥2 times ULN: Children ≥3 years and Adolescents: Discontinue treatment; there is no experience with reintroduction.

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; patients 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.

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 [contains corn starch]

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): $268.28

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): $268.28

125 mg (per each): $268.28

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.

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.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 2]).

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 2023; NIOSH 2024; 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 as follows, must be dispensed with this medication:

Tracleer: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021290s039,209279s005lbl.pdf

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 (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).

Metabolism/Transport Effects

Substrate of CYP2C9 (Minor), CYP3A4 (Minor), OATP1B1/1B3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces 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 drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

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

ALfentanil: CYP3A4 Inducers (Moderate) may decrease 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

Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor

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

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

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

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

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

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

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

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

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

Atazanavir: Bosentan may decrease serum concentration of Atazanavir. Atazanavir may increase 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 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 serum concentration of Atorvastatin. Risk C: Monitor

Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid

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

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

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

Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Bedaquiline. Risk X: Avoid

Belumosudil: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider Therapy Modification

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

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

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

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

Brigatinib: CYP3A4 Inducers (Moderate) may decrease 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

Bulevirtide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider Therapy Modification

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

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

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification

Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor

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

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

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

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

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

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

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

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

Clarithromycin: Bosentan may increase active metabolite exposure of Clarithromycin. Specifically, bosentan may increase concentrations of 14-hydroxyclarithromycin. Bosentan may decrease serum concentration of Clarithromycin. Clarithromycin may increase 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 serum concentration of Clindamycin (Systemic). Risk C: Monitor

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

Cobicistat: May increase serum concentration of Bosentan. Bosentan may decrease serum concentration of Cobicistat. 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 serum concentration of Cobimetinib. Risk X: Avoid

Codeine: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Codeine. Risk C: Monitor

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

Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification

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

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

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

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

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

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

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

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

Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid

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

Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Enzalutamide. Risk C: Monitor

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification

Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification

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

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

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

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

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

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

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

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

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

Fexinidazole: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid

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

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

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

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

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosnetupitant. Risk C: Monitor

Fostamatinib: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fostamatinib. Risk C: Monitor

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

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

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor

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

Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor

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

GlyBURIDE: May increase hepatotoxic effects of Bosentan. GlyBURIDE may decrease serum concentration of Bosentan. Bosentan may decrease serum concentration of GlyBURIDE. Risk X: Avoid

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

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

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

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

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

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor

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

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

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

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

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

Itraconazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Itraconazole. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Itraconazole. Risk C: Monitor

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

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

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

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

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

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

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

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease 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

Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease 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

Lefamulin: CYP3A4 Inducers (Moderate) may decrease 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

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

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

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

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

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

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

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

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

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

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

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

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

Lorlatinib: CYP3A4 Inducers (Moderate) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease 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 serum concentration of Lovastatin. Risk C: Monitor

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

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

Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification

Macimorelin: Coadministration of Bosentan and Macimorelin may alter diagnostic results. Risk C: Monitor

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

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

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

Mavorixafor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavorixafor. Risk C: Monitor

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

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

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

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

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

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

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

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

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

Mitapivat: CYP3A4 Inducers (Moderate) may decrease 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 concentration of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid

Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor

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

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

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

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

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

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

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

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

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

Nirmatrelvir and Ritonavir: May increase 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 serum concentration of Nirogacestat. Risk X: Avoid

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

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

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

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

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

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

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

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

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

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

Pacritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pacritinib. Risk C: Monitor

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

Paliperidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Paliperidone. Risk C: Monitor

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

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

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

Perampanel: CYP3A4 Inducers (Moderate) may decrease 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 serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase serum concentration of Bosentan. Risk C: Monitor

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

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

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

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

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

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

Protease Inhibitors: May increase 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 serum concentration of QUEtiapine. Risk C: Monitor

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

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

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

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

Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor

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

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

Revumenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Revumenib. Risk X: Avoid

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

RifAMPin: May decrease serum concentration of Bosentan. Following the initial week of concurrent rifampin, this effect is most likely. RifAMPin may increase 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

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

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

Ripretinib: CYP3A4 Inducers (Moderate) may decrease 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 concentration of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of RisperiDONE. Risk C: Monitor

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

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor

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

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

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

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

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

Sildenafil: Bosentan may decrease serum concentration of Sildenafil. Sildenafil may increase 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 serum concentration of Simeprevir. Risk X: Avoid

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

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

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

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

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

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

Sparsentan: May increase adverse/toxic effects of Endothelin Receptor Antagonists. Risk X: Avoid

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

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

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

Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid

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

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

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor

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

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

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

Teniposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Teniposide. Risk C: Monitor

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

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

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

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

Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor

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

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

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

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Toremifene. Risk C: Monitor

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

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

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

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

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

Trofinetide: May increase 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 serum concentration of Tucatinib. Risk C: Monitor

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

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

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor

Vandetanib: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid

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

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

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

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

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

VinCRIStine: CYP3A4 Inducers (Moderate) may decrease serum concentration of VinCRIStine. Risk C: Monitor

Vitamin K Antagonists: Bosentan may decrease serum concentration of Vitamin K Antagonists. Risk C: Monitor

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

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

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

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

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

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

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

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

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

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

Food Interactions

Bioavailability of bosentan is not affected by food.

Reproductive Considerations

Evaluate pregnancy status prior to treatment. Exclude pregnancy prior to initiating treatment in patients who could become pregnant. Pregnancy testing is required prior to the initiation of therapy, monthly during treatment, and one month after stopping bosentan. Counsel patients on pregnancy planning, prevention, and emergency contraception. Use is contraindicated in patients who could become pregnant.

Bosentan reduces the efficacy of hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives). Do not use hormonal contraceptives as the only method of contraception. Patients may use one highly effective form of contraception (intrauterine devices [IUD] or tubal sterilization) or a combination of two methods (a hormonal contraceptive with a barrier method or two barrier methods). When a hormonal or barrier contraceptive is used, one additional method of contraception is still needed if the partner has had a vasectomy. Consult drug interactions database for more detailed information related to the use of bosentan and specific contraceptives. A missed menses or suspected pregnancy should be reported to the health care provider.

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

Pregnancy Considerations

Outcome data related to the use of bosentan during pregnancy are limited (Amann 2023, Molelekwa 2005, Streit 2009, Tokgöz 2017). Based on data from animal reproduction studies, use during pregnancy may cause major birth defects. Use is contraindicated in patients who are pregnant.

Agents other than bosentan are recommended for treating systemic sclerosis during pregnancy (ACR [Sammaritano 2020]; Lazzaroni 2023). Patients with pulmonary arterial hypertension (PAH) are encouraged to avoid becoming pregnant (ESC/ERS [Humbert 2022]).

Breastfeeding Considerations

Bosentan is present in breast milk.

Data related to the presence of bosentan in breast milk are available from one case report. The lactating mother was taking bosentan 125 mg twice daily. Breast milk was sampled over 24 hours on days 637 and 651 postpartum. The infant received breast milk ±3 times/day with complementary foods. The highest concentration of bosentan in breast milk occurred 5 hours and 55 minutes after the maternal dose (86.1 mcg/L). The average bosentan breast milk concentration based on AUC0-12h was 49 mcg/L. Authors of the study calculated the dose of bosentan via breast milk for this infant to be 0.29 mcg/kg/day (sampling day 1) and 0.6 mcg/kg/day (sampling day 2), providing a relative infant dose (RID) of 0.01% and 0.02%, respectively, compared to the weight adjusted maternal dose (maternal weight 83 kg). This child was older and receiving limited volumes of breast milk; therefore, the authors also calculated the estimated infant dose of bosentan via breast milk to be 7.43 mcg/kg/day, providing a RID of 0.24% compared to the weight adjusted maternal dose for an infant receiving 150 mL/kg/day of breast milk. Bosentan metabolites were not evaluated. Adverse events were not observed in the infant (Nauwelaerts 2022). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

Due to the potential for serious adverse reactions in the breastfed infant (eg, fluid retention, hepatotoxicity), 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 patients who could become pregnant (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 ETA and ETB receptors, with a slightly higher affinity for the A subtype.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: ~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;
  • (DO) Dominican Republic: Tracleer;
  • (EC) Ecuador: Bosental | Endotan | Hasnub | 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: Bocleer | 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 | Tracleer | 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 | Silkay;
  • (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;
  • (PA) Panama: Buntrexil;
  • (PE) Peru: Canabosen | Pulmofirst | Tracleer | Usenta;
  • (PK) Pakistan: Bosecard | Bosent | Bosentan | Bosmon | Bosotec | Bozpah | Bsantan;
  • (PL) Poland: Bopaho | Bosentan celon | Bosentan ranbaxy | 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 | Bosentan advanced | Bozentan canon | Tracleer | Tracleer dt | Vasenex;
  • (SA) Saudi Arabia: Bosentor | Gonista | 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 | Misenbo | Ravenell | Trasenbin | Trasenib
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