Q.01

What does the bosentan REMS program require?

The Bosentan REMS is a single shared-system REMS whose goal is to reduce the risk of hepatotoxicity (liver injury). It does this through elements to assure safe use (ETASU) and an implementation system: prescribers and pharmacies must be certified, patients must be enrolled, liver function must be tested monthly, and every dispense needs authorization. It has no Medication Guide or communication plan element [1].

Approach: I used the FDA's approved REMS listing for the Bosentan Shared System REMS, last updated 03/03/2026. The FDA says this page is a general summary and does not replace the approved REMS Document.

Scope and history

  • The stated objective is that "Prescribers monitor patient's liver enzymes monthly during treatment as described in the Prescribing Information."
  • The REMS covers Tracleer (NDA 021290 and NDA 209279, Actelion) and generic bosentan under ANDAs from Zydus, Natco, Sun, Amneal, PH Health and Watson. The newest addition is Zydus ANDA 213981, on 02/17/2026.
  • On 04/26/2019 the program became a single shared system for Tracleer and its ANDAs. That change also removed the Medication Guide as a REMS element.
  • On 11/05/2025 the REMS goal and materials were revised to remove references to embryo-fetal toxicity, so hepatotoxicity is now the only risk the REMS addresses [1].

Prescribers must:

  • To get certified: review the Prescribing Information and the Prescriber Guide, then enroll using the Prescriber Enrollment Form.
  • Before the first dose:
    • counsel the patient on hepatotoxicity, its signs and symptoms, when to contact the prescriber, and the REMS liver-testing requirement;
    • give the patient the Patient Guide;
    • assess liver function and document it on the Patient Enrollment Form;
    • enroll the patient and give the patient a completed copy of the form.
  • Every month during treatment: assess liver function and counsel the patient on hepatotoxicity.
  • At all times: report adverse events suggestive of hepatotoxicity to the REMS [1].

Patients:

  • Before treatment: review the Patient Guide, receive counseling, get a liver test and enroll with the prescriber.
  • Before each prescription: receive counseling from the prescriber or pharmacy, get a liver test, and confirm completion of the test with the REMS or the pharmacy.
  • At all times: tell the prescriber about any signs or symptoms of liver problems [1].

Outpatient pharmacies must:

  • To get certified: designate an authorized representative, who reviews the Pharmacy Guide and enrolls using the Outpatient Pharmacy or Chain Pharmacy Headquarters Enrollment Form; train the relevant staff.
  • Before each dispense:
    • get authorization from the REMS confirming the patient is enrolled, the prescriber and pharmacy are certified, counseling is complete, and liver testing is complete or the prescriber authorizes the refill;
    • where testing or counseling is not documented, confirm the testing or do the counseling, and submit it through the REMS Website or Contact Center.
  • Dispense no more than a 30 days' supply.
  • At all times:
    • report hepatotoxicity adverse events;
    • not distribute, transfer, loan or sell bosentan except to certified dispensers;
    • keep dispensing, training and process records;
    • comply with audits by the Applicants or a third party acting for them [1].

Inpatient pharmacies must:

  • Get certified the same way, using the Inpatient Pharmacy Enrollment Form, which since 03/03/2026 requires at least one pharmacy identifier.
  • Before dispensing: verify the patient is enrolled (or will be before discharge) and under a certified prescriber, and that counseling and liver testing are complete.
  • At discharge: dispense no more than a 15 days' supply.
  • Meet the same reporting, distribution-restriction, recordkeeping and audit obligations as outpatient pharmacies, except that the summary lists no dispensing-record requirement for them [1].

Wholesalers-distributors must:

  • Distribute only to certified pharmacies, with procedures in place to ensure that, and train the relevant staff.
  • Keep distribution and process records.
  • Submit distribution and shipment data to the REMS. Since 09/17/2024 this data must be "complete, unblended, and unblocked."
  • Comply with audits [1].

REMS materials (03/03/2026 versions): the REMS Document, enrollment forms for prescribers, patients, outpatient, inpatient and chain pharmacy headquarters, the Prescriber, Patient and Pharmacy Guides, a Fact Sheet, the Testing and Patient Counseling Reporting Form, and the REMS Website. The full approved text is in the REMS Document [1].

Q.02