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The goal of the Bosentan REMS is to mitigate the risk of hepatotoxicity
Objective: Prescribers monitor patient's liver enzymes monthly during treatment as described in the Prescribing Information
What do participants need to know?
Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.
Enroll by completing and submitting the Prescriber Enrollment Form to the
REMS.
Before treatment initiation (first dose)
Counsel the patient on the risk of hepatotoxicity associated with bosentan,
the signs and symptoms of hepatotoxicity, to contact the prescriber if the
patient has any signs or symptoms of liver problems, and REMS
requirements including the need to complete liver testing using the Patient
Guide. Provide the patient with a copy of the Patient Guide.
Assess the patient’s liver function. Document and submit to the REMS using
the Patient Enrollment Form.
Enroll the patient by completing and submitting the Patient Enrollment Form to
the REMS. Provide a completed copy of the form to the patient.
During treatment; monthly
Assess the patient’s liver function and counsel the patient on the risk of
hepatotoxicity.
At all times
Report adverse events suggestive of hepatotoxicity to the REMS.
Patients who are prescribed bosentan:
Before treatment
Review the Patient Guide.
Receive counseling from the prescriber on the risk of liver problems, the signs
and symptoms of liver problems, the need to contact the prescriber if you have
any signs or symptoms of liver problems, and the need to complete liver
testing using the Patient Guide.
Get a liver test.
Enroll in the REMS by completing the Patient Enrollment Form with the
prescriber. Enrollment information will be provided to the REMS.
During treatment; before each prescription
Receive counseling from the prescriber or pharmacy on the risk of liver
problems associated with bosentan treatment.
Get a liver test.
Adhere to the safe use condition: Communicate with the REMS or pharmacy to
confirm completion of liver testing.
At all times
Inform the prescriber if you have any signs or symptoms of liver problems as
described in the Patient Guide.
Outpatient pharmacies that dispense bosentan must:
To become certified to dispense
Designate an authorized representative to carry out the certification process
and oversee implementation and compliance with the REMS on behalf of the
pharmacy.
Have the authorized representative review the Pharmacy Guide.
Have the authorized representative enroll by completing and submitting the
Outpatient Pharmacy Enrollment Form or Chain Pharmacy Headquarters
Enrollment Form to the REMS.
Train all relevant staff involved in dispensing bosentan on the REMS
requirements using the Pharmacy Guide.
Before dispensing
Obtain authorization to dispense each prescription by contacting the REMS to
verify the patient is enrolled, the prescriber is certified, the pharmacy is
certified, if counseling is complete, and liver testing is complete or the
prescriber authorizes the refill.
For patients without documented testing: Communicate with the patient or
prescriber to confirm testing. Document and submit the confirmation of
testing using the REMS Website or Contact Center.
For patients without documented counseling: Counsel the patient on the risk
of hepatotoxicity. Document and submit the confirmation of counseling using
the REMS Website or Contact Center.
Dispense no more than a 30 days’ supply.
To maintain certification to dispense
Have a new authorized representative enroll by completing and submitting the
Outpatient Pharmacy Enrollment Form or Chain Pharmacy Headquarters
Enrollment Form, if the authorized representative changes to the REMS.
At all times
Report adverse events suggestive of hepatotoxicity to the REMS.
Not distribute, transfer, loan, or sell bosentan, except to certified dispensers.
Maintain records of dispensing.
Maintain records of training.
Maintain records that all processes and procedures are in place and are being
followed.
Comply with audits carried out by the Applicants or a third party acting on
behalf of the Applicants to ensure that all processes and procedures are in
place and are being followed.
Inpatient pharmacies that dispense bosentan must:
To become certified to dispense
Designate an authorized representative to carry out the certification process
and oversee implementation and compliance with the REMS on behalf of the
pharmacy.
Have the authorized representative review the Pharmacy Guide.
Have the authorized representative enroll by completing and submitting the
Inpatient Pharmacy Enrollment Form to the REMS.
Train all relevant staff involved in dispensing bosentan on the REMS
requirements using the Pharmacy Guide.
Establish processes and procedures to verify the patient is enrolled or will be
enrolled prior to discharge, the patient is under the care of a certified
prescriber, counseling is complete, and liver testing is complete.
Before dispensing
Verify the patient is enrolled or will be prior to discharge, the patient is under
the care of a certified prescriber, the pharmacy is certified, counseling on the
risk of hepatotoxicity is complete, and that liver testing is complete.
At discharge
Dispense no more than a 15 days’ supply.
To maintain certification to dispense
Have a new authorized representative enroll by completing and submitting the
Inpatient Pharmacy Enrollment Form, if the authorized representative changes
to the REMS.
At all times
Report adverse events suggestive of hepatotoxicity to the REMS.
Not distribute, transfer, loan, or sell bosentan, except to certified dispensers.
Maintain records of training.
Maintain records that all processes and procedures are in place and are being
followed.
Comply with audits carried out by the Applicants or a third party acting on
behalf of the Applicants to ensure that all processes and procedures are in
place and are being followed.
Wholesalers-distributors that distribute bosentan must:
To be able to distribute
Establish processes and procedures to ensure that bosentan is distributed only
to certified pharmacies.
Train all relevant staff involved in distribution on the REMS requirements.
At all times
Distribute only to certified pharmacies.
Maintain records of drug distribution.
Maintain records that all processes and procedures are in place and are being
followed.
Maintain and submit distribution and shipment data to the REMS.
Comply with audits carried out by the Applicants or a third party acting on
behalf of the Applicants to ensure that all processes and procedures are in
place and are being followed.
What materials are included in the REMS?
The REMS includes a REMS Document.
In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Bosentan REMS, see the DailyMed link on the Products tab.
This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters,
and posted here as they become available.
What updates have been made to the REMS?
Date
Summary of change
03/03/2026
Modified to consist of:
Removal of the required pharmacy identifiers from the Chain Pharmacy Headquarters Enrollment Form
Modifying the Inpatient Pharmacy Enrollment Form to require at least one pharmacy identifier
Editorial and formatting updates to the REMS Document, Pharmacy Enrollment Forms, and REMS Website
11/05/2025
Modified to revise the REMS goal and REMS materials to remove references to the risk of embryo-fetal toxicity
02/21/2025
Modified to include:
Changes to the Bosentan Applicants’ requirements, including shortening the time
period for notifying newly certified prescribers and pharmacies and maintaining
records of Bosentan Wholesaler-Distributor distribution and Pre-Dispense
Authorization.
Changes to the REMS audit requirements for certified pharmacies.
09/17/2024
Modified to:
Remove the mail modality for receiving stakeholder communication
Update wholesaler-distributor requirements to provide complete, unblended,
and unblocked distribution data, including information on shipments to
pharmacies, to the Bosentan REMS administrator in order to verify compliance
with the Bosentan REMS
Remove the “Important REMS Update” banner from the REMS Website
Update the REMS Document formatting to include the risk of embryofetal
toxicity and hepatotoxicity in the Administrative Information section and adding
section VI for Statutory Elements
04/29/2022
Modified to:
Changes to the outpatient pharmacy operations to verify safe use conditions for the
REMS Pre-Dispense Authorization (PDA).
Addition of the Prescriber Designee role on the REMS website to allow prescribers
to delegate certain administrative activities.
Changes to the REMS website to allow certified pharmacies to enter testing and
counseling information through the REMS website and allow pharmacists requesting a PDA to confirm counsling information.
Changes to the pre-recorded messages in the Interactive Voice Response (IVR)
system to align with the proposed modifications and new workflow.
Conversion of the REMS Document to the new, standardized format.
05/20/2019
Revised to make an editorial change.
04/26/2019
Modified to establish a Single Shared System REMS for the elements to assure safe use and the implementation system required for the reference listed drug (RLD) Tracleer and ANDAs referencing Tracleer, called the Bosentan REMS Program. This modification also removes the Medication Guide as an element of the REMS.
Disclaimer: This webpage provides general information about REMS programs
to various REMS participants (e.g., patients, pharmacies, and healthcare providers).
The summary information provided herein is not comprehensive and may not include
all of the information relevant to REMS participants. This webpage does not
constitute a replacement, modification, or revision of the approved REMS document,
including any appended REMS materials. Refer to the approved REMS document
for complete information on the REMS requirements for each approved application.
