Frequently Asked Questions (FAQs)
What is a REMS?
A Risk Evaluation and Mitigation Strategy (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 manufacturers of bosentan have worked with the FDA to develop the Bosentan Single Shared System REMS Program to mitigate the risk of hepatotoxicity and embryo-fetal toxicity.
What is the Bosentan REMS Program?
The Bosentan REMS Program is a single shared program for brand and generic bosentan medication 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.
What is the goal of the Bosentan REMS Program?
The goal of the Bosentan REMS Program is to mitigate the risk of hepatotoxicity and embryo-fetal toxicity associated with bosentan by:
  • Ensuring prescribers are educated on the following:
    • the risks of hepatotoxicity and embryo-fetal toxicity
  • Ensuring prescribers are educated on and adhere to the following:
    • counseling patients about these risks and the need for monthly monitoring
    • enrolling patients in the Bosentan REMS Program
    • monitoring patients at baseline and monthly
  • Ensuring that pharmacies are educated on the following:
    • the risks of hepatotoxicity and embryo-fetal toxicity
  • Ensuring that pharmacies are educated on and adhere to the following:
    • confirming that the appropriate patient monitoring and counseling has occurred before dispensing bosentan
  • Ensuring that patients are informed about:
    • the risks of hepatotoxicity and embryo-fetal toxicity
    • appropriate baseline and monthly patient monitoring
    • appropriate contraception
What are the different roles of healthcare staff in the Bosentan REMS Program?
There are three different roles in the Bosentan REMS Program:
  • Prescriber
  • Pharmacy Authorized Representative
  • Pharmacy Staff
The high-level certification requirements for each role are presented in the table below.

Role Description
Prescriber Prescriber Certification Process
  • Review the Prescribing Information for bosentan.
  • Review the Bosentan REMS Program Prescriber Guide.
  • Enroll in the Bosentan REMS Program by completing the Bosentan REMS Prescriber Enrollment Form online here, by submitting via fax to 1-800-730-8231, or mail to the Bosentan REMS Program at P.O. Box 29080, Phoenix, AZ 85038.
Authorized Representative (Outpatient Pharmacy) Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for individual pharmacy locations that dispense bosentan for outpatient use, such as retail, specialty, and mail order, must complete and submit the Bosentan REMS Program Outpatient Pharmacy Enrollment Form online here, by faxing to 1-800-730-8231, or mailing to the Bosentan REMS Program at P.O. Box 29080, Phoenix, AZ 85038.
  • For pharmacies that can process claims electronically, additional steps are needed to connect its pharmacy management system to the Bosentan REMS Program. Contact the Bosentan REMS Program Contact Center at 1-866-359-2612 for additional information.
Authorized Representative (Chain Pharmacy) Chain Pharmacy Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for multiple location retail pharmacies that dispense bosentan for outpatient use and have a pharmacy headquarters that coordinates pharmacy enrollment in the Bosentan REMS Program must complete and submit the Bosentan REMS Program Chain Pharmacy Headquarters Enrollment Form online here, by faxing to the Bosentan REMS Program Contact Center at 1-800-730-8231, or by mailing it to the Bosentan REMS Program at P.O. Box 29080, Phoenix, AZ 85038.
  • Work with an Account Manager from the pharmacy's network provider to complete the certification process. For questions on how to contact an Account Manager, call the Bosentan REMS Program Contact Center at 1-866-359-2612.
Authorized Representative (Inpatient Pharmacy) Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for pharmacy locations that dispense bosentan for inpatient use, such as pharmacies in hospitals, hospices, long-term care facilities, and prisons, must complete and submit the Bosentan REMS Program Inpatient Pharmacy Enrollment Form online here, by faxing to the Bosentan REMS Program Contact Center at 1-800-730-8231, or by mailing to the Bosentan REMS Program at P.O. BOX 29080, Phoenix, AZ 85038.
Pharmacy Staff Pharmacy Staff Enrollment Process
  • Be trained on the Bosentan REMS Program by your pharmacy's Authorized Representative.
  • Enroll as pharmacy staff on the Bosentan REMS Program Website here.
What are the hours of the Bosentan REMS Program Contact Center?
The Bosentan REMS Program Contact Center (1-866-359-2612) hours of operation are Monday through Friday, 8 AM to 8 PM Eastern Time.

Stakeholders can access the Bosentan REMS Program Website at www.BosentanREMSProgram.com 24 hours a day, 7 days a week.
How can a prescriber become certified in the Bosentan REMS Program?
Prescribers can certify in the Bosentan REMS Program by completing the Bosentan REMS Prescriber Enrollment Form online here, by submitting it to the Bosentan REMS Program by fax at 1-800-730-8231 or by mailing it to the Bosentan REMS Program at P.O. Box 29080, Phoenix, AZ 85038.
Who can certify as a prescriber in the Bosentan REMS Program?
Any medical professional prescribing bosentan must become certified in the Bosentan REMS Program prior to prescribing bosentan.
How can a prescriber find pharmacies that are certified in the Bosentan REMS Program?
A prescriber can find certified pharmacies by calling the Bosentan REMS Program Contact Center at 1-866-359-2612 or by utilizing the "Pharmacy Lookup" feature on the Bosentan REMS Program Website here.
What are the different pharmacy certification types in the Bosentan REMS Program?
All inpatient, outpatient, and chain pharmacies must certify in the Bosentan REMS Program to purchase and dispense bosentan.

Pharmacies participating in the Bosentan REMS Program must determine the company's pharmacy type based on the definitions below:

Pharmacy Type Definition
Outpatient Pharmacy For the purposes of this REMS outpatient pharmacies include but are not limited to retail, specialty, mail order, and closed system pharmacies.
Chain Pharmacy For the purposes of this REMS chain pharmacies are retail pharmacies with multiple locations that dispense bosentan for outpatient use and have a pharmacy headquarters that coordinates pharmacy enrollment in the Bosentan REMS Program.
Inpatient Pharmacy For the purposes of this REMS inpatient pharmacies include but are not limited to pharmacies in hospitals, hospices, long-term care facilities, and prisons.
How does a pharmacy certify in the Bosentan REMS Program?
Outpatient Pharmacy Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for individual pharmacy locations that dispense bosentan for outpatient use, such as retail, specialty, and mail order pharmacies, must complete and submit the Bosentan REMS Program Outpatient Pharmacy Enrollment Form online here, by faxing it to the Bosentan REMS Program Contact Center at 1-800-730-8231, or by mailing it to the Bosentan REMS Program at P.O. BOX 29080, Phoenix, AZ 85038.
  • For pharmacies that can process claims electronically, additional steps are needed to connect its pharmacy management system to the Bosentan REMS Program. Contact the Bosentan REMS Program Contact Center at 1-866-359-2612 for additional information.
Chain Pharmacy Chain Pharmacy Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for multiple location retail pharmacies that dispense bosentan for outpatient use and have a pharmacy headquarters that coordinates pharmacy enrollment in the Bosentan REMS Program must complete and submit the Bosentan REMS Program Chain Pharmacy Headquarters Enrollment Form online here, by faxing it to the Bosentan REMS Program Contact Center at 1-866-359-2612, or by mailing it to the Bosentan REMS Program at P.O. BOX 29080, Phoenix, AZ 85038.
  • Chain pharmacies will work with an Account Manager from the pharmacy's network provider to complete the certification process. For questions on how to contact your Account Manager, contact the Bosentan REMS Program Contact Center at 1-866-359-2612.
Inpatient Pharmacy Authorized Representative Certification Process
  • Review the Bosentan REMS Program Pharmacy Guide.
  • Authorized representatives for pharmacy locations that include but are not limited to pharmacies in hospitals, hospices, long-term care facilities, and prisons, must complete and submit the Bosentan REMS Program Inpatient Pharmacy Enrollment Form online here, by faxing it to the Bosentan REMS Program Contact Center at 1-800-730-8231, or by mailing it to the Bosentan REMS Program at P.O. BOX 29080, Phoenix, AZ 85038.
What is an authorized representative?
In general, an authorized representative for a pharmacy:
  • Coordinates the activities required for the pharmacy and/or pharmacy staff in the Bosentan REMS Program
  • Establishes and implements processes and procedures to ensure compliance with the safe-use conditions of the Bosentan REMS Program
  • Maintains documentation that all processes and procedures are in place and are being followed for the Bosentan REMS Program and provide upon request to the Bosentan Sponsors or a third party acting on behalf of the Bosentan Sponsors
  • Complies with audits by the Bosentan Sponsors or a third party acting on behalf of the Bosentan Sponsors to ensure that all processes and procedures are in place and are being followed for the Bosentan REMS Program
How do closed healthcare system pharmacies, such as the VA, certify in the Bosentan REMS Program?
Closed healthcare system pharmacies certify in the Bosentan REMS Program, and ensure all safe use conditions are met prior to dispensing bosentan to a patient, by using the same process as outpatient pharmacies that do NOT support electronic communication verification.
What is a pre-dispense authorization (PDA)?
A PDA is verification sent to outpatient and chain pharmacies by the Bosentan REMS Program, authorizing the pharmacy to dispense bosentan to an eligible patient. The following safe-use conditions are verified prior to every bosentan dispense:
  • Prescriber is certified in the Bosentan REMS Program
  • Patient is enrolled in the Bosentan REMS Program (for inpatient pharmacies, patient enrollment by his/her prescriber must occur prior to discharge)
  • Current completed liver function testing for the patient is confirmed
  • If the patient is a female of reproductive potential, a current completed pregnancy test for the patient is confirmed
  • Current hepatotoxicity counseling for all patients, and counseling for embryo-fetal toxicity and the need to use reliable contraception for females of reproductive potential is confirmed
    • If counseling is not confirmed in the Bosentan REMS Program, a PDA will be issued if all other safe-use conditions are met. The pharmacy must call the Bosentan REMS Program Contact Center to receive guidelines for counseling the patient before bosentan is dispensed. The Contact Center will provide counseling guidelines to the pharmacy. The pharmacy is required to counsel the patient according to the guidelines from the Contact Center
      • The Contact Center agents will be available during normal business hours. The Contact Center agent will provide the counseling guidelines and document the counseling
      • An interactive voice response system will be available 24/7. The system will provide the counseling guidelines and document the counseling
How do I obtain a pre-dispense authorization (PDA)?
Pharmacies can obtain a PDA by one of the following methods:
  • Enable its pharmacy management system to support electronic telecommunication verification with the Bosentan REMS Program
  • Access the Bosentan REMS Program Website here
  • Call the Bosentan REMS Program Contact Center at 1-866-359-2612
To verify the safe use conditions in the Bosentan REMS Program, the certified outpatient and chain pharmacy must submit the following information:
  • Patient First Name
  • Patient Last Name
  • Patient Date of Birth
  • Patient Zip Code
  • Prescriber Identifier (e.g. DEA or NPI)
  • Date of Fill
  • Days' Supply
  • Quantity
  • Product / NDC
Once a PDA is obtained, the outpatient and chain pharmacy can dispense bosentan to the patient.
Is an inpatient pharmacy required to obtain a pre-dispense authorization (PDA)?
No, inpatient pharmacies are not required to obtain a PDA, but must:

Dispense bosentan to patients only after calling the Bosentan REMS Contact Center at 1-866-359-2612, accessing the Bosentan REMS Program Website* here or accessing the patient's medical records to:

  • Verify that the patient is under the supervision and care of a prescriber who is certified

  • Verify that the patient is enrolled or will be enrolled prior to discharge

*Authorized Representatives and enrolled pharmacy staff in an inpatient pharmacy can check inpatient REMS requirements from their dashboard on the Bosentan REMS Program Website. To check inpatient REMS requirements, the user enters the following data:

  • Patient data: First Name, Last Name, Date of Birth, Zip Code (Required)
  • Prescription data: Date of Fill, Manufacturer, NDC number, Days Supply, Quantity (Optional)
  • Prescriber identifier: DEA or NPI (at least one identifier is required)
What activity may an outpatient or chain pharmacy perform if a pre-dispense authorization (PDA) is not issued?
If a PDA is not issued because one or more of the safe-use conditions have not been met prior to dispensing bosentan, outpatient and chain pharmacies may perform the corresponding activity to address the reason that a PDA was not issued:
  • Certify the pharmacy in the Bosentan REMS Program
  • Contact the prescriber or the Bosentan REMS Program to notify that the prescriber certification is required in the Bosentan REMS Program before bosentan can be dispensed
  • Contact the prescriber or the Bosentan REMS Program to notify the prescriber that the patient must be enrolled in the Bosentan REMS Program before bosentan can be dispensed
  • Contact the Bosentan REMS Program to notify the patient or the patient's prescriber that appropriate lab tests are required in the Bosentan REMS Program before bosentan can be dispensed
What happens when a patient tries to fill a prescription at a pharmacy that is not certified?
If a pharmacy is not certified in the Bosentan REMS Program, a patient will be unable to obtain bosentan at that pharmacy location, even if the patient meets other program element requirements as defined by the Bosentan REMS Program. Pharmacies must become certified in the Bosentan REMS Program in order to dispense bosentan to patients.
Will pharmacies that are not certified be able to order bosentan?
No, if a pharmacy is not certified in the Bosentan REMS Program, the pharmacy will not be approved to receive bosentan.
How will my wholesaler/distributor know whether the pharmacy is certified in the Bosentan REMS Program, so I can order bosentan?
Wholesaler/distributors must verify the pharmacy is certified in the Bosentan REMS Program prior to distributing bosentan to a pharmacy. Wholesaler/distributors may access the database of certified pharmacies provided by the Bosentan REMS Program, utilize the "Pharmacy Look Up" on the Bosentan REMS Program Website or contact the Bosentan REMS Program for confirmation of pharmacy certification.
What if the authorized representative leaves the pharmacy?
If the authorized representative leaves the pharmacy, a new authorized representative must notify the Bosentan REMS Program of the change in the authorized representative by certifying in the Bosentan REMS Program.
Who is considered pharmacy staff?
Any pharmacist or pharmacy employee in a certified pharmacy may assume the role of pharmacy staff to conduct basic program functions through the Bosentan REMS Program Website.
What activities may a pharmacy staff member perform?
  • Pharmacy staff in outpatient pharmacies that do NOT support electronic communication verification with the Bosentan REMS Program system will be able to request a PDA
  • Pharmacy staff in inpatient pharmacies will be able to verify prescriber certification and patient enrollment
What is a refill dispense exception?
The Bosentan REMS Program provides prescribers to apply clinical judgment and authorize continued dispensing of bosentan to enrolled patients when a patient's testing could not be confirmed in a given month and for extended travel outside of the United States. In order for a pharmacy to dispense to a patient, the prescriber must authorize a refill dispense exception.
A refill dispense exception allows a prescriber to authorize a patient to receive up to a 30-day supply of bosentan without confirmed pregnancy and/or liver function testing. The refill dispense exception also allows the prescriber to authorize up to a 90-day supply of bosentan for extended travel outside of the United States of more than 30 days.
In order for a patient to be eligible to receive a refill dispense exception due to testing not being confirmed in a given month:
  • The patient must be enrolled in the Bosentan REMS Program
  • The patient must have confirmed testing on file for the previous month
  • The prescriber must attest that the benefits of receiving bosentan outweigh the risks of hepatotoxicity and embryo-fetal toxicity associated with bosentan
In order for a patient to be eligible to receive a refill dispense exception for extended travel outside of the United States:
  • The patient must be enrolled in the Bosentan REMS Program
  • The patient must have confirmed testing on file for the previous month
  • The patient must be traveling outside of the United States for more than 30 days
  • The prescriber must attest that the benefits of receiving bosentan outweigh the risks of hepatotoxicity and embryo-fetal toxicity associated with bosentan
  • The prescriber must attest to continue to counsel the patient about the risk of embryo-fetal toxicity and 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 monthly while traveling outside of the United States
    • Test confirmation is not required to be provided to the Bosentan REMS Program while the patient is traveling outside of the United States
How does a prescriber authorize a refill dispense exception?
Only certified prescribers can authorize a refill dispense exception by:
  • Calling the Bosentan REMS Program Contact Center at 1-866-359-2612
  • Documenting the refill dispense exception authorization through the Bosentan REMS Program Website
Do patients need to be enrolled in the Bosentan REMS Program in order to receive bosentan?
Yes, any patient prescribed bosentan must be enrolled in the Bosentan REMS Program by the patient's prescriber. Patients in an inpatient setting must be enrolled prior to discharge.
How are patients enrolled in the Bosentan REMS Program?
Patients can be enrolled by prescribers online here, by faxing the Bosentan REMS Program Patient Enrollment Form to the Bosentan REMS Program Contact Center at 1-800-730-8231, or by mailing it to the Bosentan REMS Program at P.O. BOX 29080, Phoenix, AZ 85038. Patients or their legal guardian must also sign the Bosentan REMS Program Patient Enrollment Form online or on a hard copy of the form to complete the patient enrollment process.
How is Reproductive Potential Status defined for female patients?
Females of Reproductive Potential
  • Females of reproductive potential include girls who have entered puberty and all females who have a uterus and have not passed through menopause
  • For the purposes of this REMS, puberty includes girls who are at least Tanner Stage 3 and have not yet had a menses (premenarchal)

Females of Non-Reproductive Potential
  • Pre-pubertal Females: Females who are at Tanner Stages 1 and 2 are not considered to be of reproductive potential
  • Post-menopausal Females: Females who have passed through menopause. Menopause is defined as 12 months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy) or post-surgical form bilateral oophorectomy
  • Females with other medical reasons for permanent, irreversible infertility
How are patient monthly tests and counseling reported to the Bosentan REMS Program?
Prescribers may report that the appropriate monthly tests, including liver function tests for all patients, pregnancy test for females of reproductive potential, and appropriate counseling for all patients, 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 here
  • Calling the Bosentan REMS Program Contact Center at 1-866-359-2612
Note: Use of the Bosentan REMS Program Testing and Patient Counseling Reporting Form is voluntary.
What are the testing requirements for patients?
Liver function test for every patient and pregnancy status for females of reproductive potential:
  • Order and review liver function tests for all patients:
    • Prior to initiating treatment
    • Monthly during treatment
  • Order and review pregnancy tests for females of reproductive potential:
    • Prior to initiating treatment
    • Monthly during treatment
    • One month after ending bosentan treatment
What action does a prescriber need to take if previously certified in the Tracleer REMS Program?
Prescribers that were certified in the Tracleer REMS Program will be automatically certified in the Bosentan REMS Program.

Beginning June 3, 2019 bosentan is only available through the Bosentan REMS Program, and includes all brand and generic bosentan products. As of June 3, 2019 you can verify whether your patient's pharmacy is authorized to dispense bosentan by visiting the Bosentan REMS Program Website here. Until June 2, 2019 patients will continue to have access to Tracleer through the Tracleer REMS Program and certified specialty pharmacies.
If my patient was enrolled in the Tracleer REMS Program, do I need to re-enroll him/her in the Bosentan REMS Program?
No, patients that were enrolled in the Tracleer REMS Program are automatically enrolled in the Bosentan REMS Program. No further action is required for patients that were enrolled in the Tracleer REMS Program.
What action does a pharmacy need to take if previously certified in the Tracleer REMS Program?
Specialty pharmacies that were certified in the Tracleer REMS Program must complete certification in the Bosentan REMS Program.

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