bosentan
Risks of Hepatotoxicity and Embryo-Fetal Toxicity
Bosentan is available only through a restricted distribution program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS) because of the risk of hepatotoxicity (5.2): Elevations of liver aminotransferases (ALT, AST) and liver failure have been reported with bosentan (5.1).
- Measure liver aminotransferases prior to initiation of treatment and then monthly (2.1, 5.1).
- Discontinue bosentan if aminotransferase elevations are accompanied by signs or symptoms of liver dysfunction or injury or increases in bilirubin ≥2×ULN (2.4, 5.1).
Based on animal data, bosentan may cause fetal harm if used during pregnancy (4.1, 5.3, 8.1).
- Females of reproductive potential: Exclude pregnancy before initiating treatment. Use effective contraception prior to initiation of treatment, during treatment and for one month after stopping bosentan (2.1, 4.1, 5.3, 8.1, 8.3).
- When pregnancy is detected, discontinue bosentan as soon as possible (5.3).
Monitoring data
- Avoid use in patients with elevated aminotransferases (> 3 x ULN) at baseline because monitoring liver injury may be more difficult.
Dosage Adjusment and Monitoring in Patients Developing Aminotransferase Abnormalities:
ALT/AST Levels Treatment and Monitoring Recommendations - > 3 and equal to or less than 5 x ULN: Confirm by another aminotransferase test; if confirmed, reduce the daily dose or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If the aminotransferase levels return to pre-treatment values, continue or re-introduce the treatment as appropriate (see below).
- > 5 and equal to or less than 8 x ULN: Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks. Once the aminotransferase levels return to pre-treatment values, consider re-introduction of the treatment (see below).
- > 8 x ULN: Treatment should be stopped and re-introduction of TRACLEER@ should not be considered. There is no experience with re-introduction ofTRACLEER@ in these circumstances.
Pregnancy
- Exclude pregnancy prior to initiation of therapy. Negative urine/serum pregnancy test performed during first 5 days of normal menstrual period and > 11 days after the last unprotected act of sexual intercourse. Follow-up serum pregnancy tests should be obtained monthly in women of child bearing potential.
- Hormonal contraception may not be reliable due to a drug interaction and should not be used as sole contraceptive
Patient counseling
REMS
Medical guidelines
Package inserts
Additional information
Keywords: Tracleer
Updated: November 2025