A REMS is a strategy to manage known or potential serious risks associated with a drug product and is required by the Food and Drug Administration (FDA) to ensure the benefits of a drug outweigh its risks. The Bosentan REMS Program is a single shared REMS program for brand and generic approved bosentan medications for the treatment of pulmonary arterial hypertension (PAH). Due to the risks of hepatotoxicity and embryo-fetal toxicity, bosentan is only available through the Bosentan REMS Program.

Bosentan REMS Program Overview
  • All healthcare providers must certify in the Bosentan REMS Program and comply with the Bosentan REMS Program requirements in order to prescribe a bosentan product
  • All patients must be enrolled in the Bosentan REMS Program. Enrolled patients must comply with the Bosentan REMS Program requirements in order to receive bosentan:
    • Patients must agree to complete liver function tests, and pregnancy tests as appropriate for the patient's reproductive potential classification prior to receiving bosentan
    • All patients must agree to be counseled on the Bosentan REMS Program and the risks of treatment with bosentan
    • All patients must agree to be contacted about completing required monthly testing and counseling
  • For all patients:
    • Prescribers must counsel all patients on the risk of hepatotoxicity associated with bosentan, the signs and symptoms of hepatotoxicity, and program requirements including the need to complete liver function testing and, as appropriate, pregnancy testing by reviewing the Bosentan REMS Program Guide for Patients to each patient
    • Prescribers must complete the Bosentan REMS Program Patient Enrollment Form with every bosentan patient and submit the form to the Bosentan REMS Program prior to initiating treatment
    • Counsel patients who fail to comply with program requirements
    • Prescribers must order and review liver function test results before bosentan treatment initiation
    • Prescribers must order and review monthly liver function test results
    • Prescribers must report all adverse events including those suggestive of hepatotoxicity to the Bosentan REMS Program
  • For all female patients:
    • Prescribers must determine the reproductive potential status of every female before initiating bosentan treatment
    • Prescribers must report a change or misclassification in reproductive potential status by submitting a Bosentan REMS Program Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form to the Bosentan REMS Program within 10 business days of becoming aware of the change
    • Prescribers must report any pregnancy and all available information during treatment with bosentan to the Bosentan REMS Program
  • For females of reproductive potential:
    • Prescribers must counsel patients about the risk of embryo-fetal toxicity and the need to use reliable contraception prior to initiating treatment, during bosentan treatment, and for one month after ending treatment
    • Prescribers must counsel the patient to immediately contact her healthcare provider if she misses a menstrual period or suspects pregnancy
    • Prescribers must order and review pregnancy tests prior to initiation of bosentan treatment, monthly during treatment, and for one month after ending treatment
  • For pre-pubertal female patients:
    • Prescribers must counsel the patient and/or a parent/legal guardian about the risk of embryo-fetal toxicity
    • Prescribers must counsel the patient and/or a parent/legal guardian to immediately contact her healthcare provider if she begins to menstruate
    • Prescribers must evaluate patients age 8 years and older at least annually for any change in reproductive status and submit a Bosentan REMS Program Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form to the Bosentan REMS Program within 10 business days of becoming aware of the change
  • Prescribers may report that the appropriate monthly tests and counseling, comprising liver function tests (for all patients), pregnancy tests for females of reproductive potential, and monthly counseling have been completed by reporting it to the Bosentan REMS Program. This information can be reported by one of the following methods:
    • Submitting a Bosentan REMS Program Testing and Patient Counseling Reporting Form by fax to the Bosentan REMS Program at 1-800-730-8231
    • Completing the Bosentan REMS Program Testing and Patient Counseling Reporting Form online at www.BosentanREMSProgram.com
    • Calling the Bosentan REMS Program at 1-866-359-2612
  • Note: Use of the Bosentan REMS Program Testing and Patient Counseling Reporting Form is voluntary.
  • Prescribers must closely monitor transaminase levels and adjust monitoring and treatment with bosentan if increases are reported
  • Prescribers must discontinue bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity or increases in bilirubin ≥2 x ULN
  • Only inpatient, outpatient and chain pharmacies certified in the Bosentan REMS Program can dispense bosentan


For additional information about the Bosentan REMS Program, please call 1-866-359-2612.