Approved Risk Evaluation and Mitigation Strategies (REMS)

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Bosentan
Shared System REMS
REMS last update: 05/20/2019

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Tracleer (bosentan) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 021290 ACTELION PHARMS LTD 04/26/2019 749e42fb-2fe0-45dd-9268-b43bb3f4081c
Tracleer (bosentan) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 209279 ACTELION PHARMS 04/26/2019 749e42fb-2fe0-45dd-9268-b43bb3f4081c
bosentan (Info at Drugs@FDA) ANDA 207760 ZYDUS PHARMS 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 206987 NATCO PHARMA LTD 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 209324 SUN PHARM 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 209742 AMNEAL PHARMS CO 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 205699 PAR PHARM INC 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 207110 WATSON LABS INC 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 208695 WEST-WARD PHARMS INT 04/26/2019
bosentan (Info at Drugs@FDA) ANDA 206002 ALVOGEN PINE BROOK 04/26/2019

What is the purpose of the REMS?

The goal of the Bosentan REMS Program is to mitigate the risk of hepatotoxicity and embryofetal toxicity associated with bosentan by:
  1. Ensuring prescribers are educated on the following:
    • the risks of hepatotoxicity and embryo-fetal toxicity
  2. 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
  3. Ensuring that pharmacies are educated on the following:
    • the risks of hepatotoxicity and embryo-fetal toxicity
  4. Ensuring that pharmacies are educated on and adhere to the following:
    • confirming that the appropriate patient monitoring and counseling has occurred before dispensing bosentan
  5. Ensuring that patients are informed about:
    • the risks of hepatotoxicity and embryo-fetal toxicity
    • appropriate baseline and monthly patient monitoring
    • appropriate contraception

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.

View application holder(s) REMS Website See Disclaimer page regarding links to external sites

Healthcare Providers who prescribe bosentan must:

To become certified to prescribe
  • Review the drug's prescribing information.
  • Review the Prescriber Guide.
  • Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
Before treatment initiation (first dose)
  • Provide the patient the Guide for Patients. | Guide for Pateints |
  • Counsel the patient on the risk of hepatotoxicity, the signs and symptoms of hepatotoxicity, and the need to complete liver function testing using the Guide for Patients.
  • Assess the patient's pretreatment liver function by ordering and reviewing a liver function test.
During treatment; before each prescription
  • Counsel the patient on program requirements if they are not complying with required testing.
  • Assess the patient's liver function by ordering and reviewing a liver function test.
  • For females of reproductive potential: assess the patient's pregnancy status by ordering and reviewing a pregnancy test.
During treatment; at least annually
  • For pre-pubertal females at least age 8 or older: Document reproductive status and submit the results using the Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form.
After treatment discontinuation; one month
  • For females of reproductive potential: assess the patient's pregnancy status by ordering and reviewing a pregnancy test.
At all times
  • For pre-pubertal females: Assess the patient’s reproductiv status.
  • Report all adverse events, including hepatoxicity, or any pregnancy to the REMS Program.
At all times; within 10 business days
  • Report a change or misclassification in reproductive status to the REMS Program using the Change in Reproductive Potential Status and Pre-pubertal Annual Verificatio Form.

Females of Reproductive Potential who are prescribed bosentan:

Before treatment initiation
  • Review the Guide for Patients. | Guide for Pateints |
  • Get a pregnancy test and liver function test.
  • Enroll in the REMS by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program. | Patient Enrollment Form |
  • Receive counseling from the prescriber on the risk of hepatoxicity, the signs and symptoms of hepatoxicity, and the risk of embryo-fetal toxicity and the need to use reliable birth control; the need to complete liver function and pregnancy testing; and that the REMS program will contact the patient to confirm of liver function an pregnancy tests.
During treatment; before each dispensing
  • Receive counseling on the risk of hepatoxicity and embryo-fetal toxicity and the need for reliable contraception during treatment and for one month after stopping treatment, to get monthly pregnancy tests, and to report a pregnancy immediately.
  • Get a pregnancy test and liver function test.
  • Adhere to the safe use condition: communicate with the REMS program to confirm completion of pregnancy testing and liver function testing.
During treatment and after treatment discontinuation for one month
  • Adhere to the safe use condition: use reliable contraception as described in the Guide for Patients. | Guide for Pateints |
  • Agree to be contacted by the REMS program if you become pregnant.
After treatment discontinuation; one month
  • Get a pregnancy test.
At all times
  • Immediately inform the prescriber if you miss a menstrual period or suspect pregnancy.

Pre-pubertal Females who are prescribed bosentan:

Before treatment initiation
  • Review the Guide for Patients. | Guide for Pateints |
  • Get a liver function test.
  • Enroll in the REMS by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS program. | Patient Enrollment Form |
  • Receive counseling from the prescriber on the risk of hepatoxicity and embryo-fetal toxicity, the signs and symptoms of hepatoxicity; the need to complete liver function testing; and that the REMS program will contact the patient to confirm of liver function tests.
During treatment; before each dispensing
  • Receive counseling on the risk of hepatotoxicity and embryo-fetal toxicity.
  • Get a liver function test.
  • Adhere to the safe use condition: communicate with the REMS Program to confirm completion of liver function testing.
At all times
  • If over the age of 8: Be monitored for a change in reproductive status.
  • Inform the prescriber if the patient begins to menstruate.

Post-Menopausal Females or Female Patients with other medical reason for permanent, irreversible infertility who are prescribed bosentan:

Before treatment initiation
  • Review the Guide for Patients. | Guide for Pateints |
  • Get a liver function test.
  • Enroll in the REMS by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS program. | Pateint Enrollment Form |
  • Receive counseling from the prescriber on the risk of hepatoxicity, the signs and symptoms of hepatoxicity; the need to complete liver function testing; and that the REMS program will contact the patient to confirm of liver funcon tests.
During treatment; before each dispensing
  • Get a liver function test.
  • Adhere to the safe use condition: communicate with the REMS Program to confirm completion of liver function testing.

Male Patients who are prescribed bosentan:

Before treatment initiation
  • Review the Guide for Patients. | Guide for Pateints |
  • Get a liver function test.
  • Enroll in the REMS by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program. | Patient Enrollment Form |
  • Receive counseling from the prescriber on the risk of hepatoxicity, the signs and symptoms of hepatoxicity; the need to complete liver function testing; and that the REMS program will contact the patient to confirm of liver function tests.
During treatment; before each dispensing
  • Get a liver function test.
  • Adhere to the safe use condition: communicate with the REMS Program to confirm completion of liver function testing.

Chain and/or 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 Program on behalf of the outpatient pharmacy.
  • Have the authorized representative review the Pharmacy Guide. | Pharmacy Guide |
  • Have the authorized representative enroll in the Bosentan REMS by completing the Outpatient Pharmacy Enrollment Form or Chain Pharmacy Headquarters Enrollment Form and submitting it to the Bosentan REMS.
  • Train all relevant staff involved in dispensing bosentan on the Bosentan REMS requirements using the Pharmac Guide.
  • Establish processes and procedures to obtain pre-dispense authorization from the Bosentan REMS Program, verify the prescriber is certified and the patient is enrolled, the patient has completed the liver function tests and each female of reproductive potential has competed the pregnancy test or the prescriber has authorized a refill, and verify if the patient has been counseled on the risk of hepatoxicity and each female of reproductive potential has been counseled on the risk of embryo-fetal toxicity and the need to use reliable contraception.
Before dispensing
  • Counsel the patient on the risk of hepatotoxicity and the need for monthly liver testing or verify that counseling was completed.
  • Verify that liver function testing was completed.
  • For females of reproductive potential: counsel the patient on the risk of embryo-fetal toxicity, the need to use reliable contraception during treatment and for one month after stopping treatment, the need to complete a monthly pregnancy test, and to inform her prescriber immediately if she suspects a pregnancy, or verify counseling as completed.
  • For Females of reproductive potential: verify that the pregnancy test was complete or the prescriber authorizes the refill.
  • Obtain authorization to dispense by contacting the REMS coordinating center.
  • Dispense no more than a 30 days' supply.
At all times
  • Report any adverse events, including hepatotoxicity, and any reports of pregnancy to the REMS Program.
  • Do not distribute, transfer, loan, or sell product, except to certified dispensers.
  • Maintain records of dispensing data for all enrolled patients.
  • Cooperate with audits carried out by the REMS program 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 Bosentan REMS on behalf of the inpatient pharmacy.
  • Have the authorized representative review the Pharmacy Guide. | Pharmacy Guide |
  • Have the authorized representative enroll in the REMS by completing the Inpatient Pharmacy Enrollment Form and submitting it to the Bosentan REMS Program
  • Train all relevant staff involved in dispensing bosentan on the Bosentan REMS requirements using the Pharmacy Guide.
  • Establish processes and procedures to verify the patient is under the supervision and care of a healthcare provider who is enrolled and a patient is enrolled or will be enrolled prior to discharge.
  • For Females of Reproductive Potential: establish processes and procedures to verify that the patient has been counseled on the risk of embryo-fetal toxicity, the need to use highly reliable contraception and emergency contraception, to get monthly pregnancy tests, and to inform the prescriber of a pregnancy immediately.
Before dispensing
  • Verify the patient is under the supervision and care of a certified prescriber.
  • Verify the patient is enrolled or will be enrolled prior to discharge.
  • Verify the patient has been counseled on the risk of hepatotoxicity and liver function testing is complete
  • For Females of Reproductive Potential: verify that the patient has been counseled on the risk of embryo-fetal toxicity and the need to use reliable contraception and pregnancy testing is complete.
At discharge
  • Dispense no more than a 15 days' supply.
At all times
  • Report any adverse events, including hepatotoxicity and any reports of pregnancy to the REMS Program.
  • Report a change or misclassification in reproductive status to the Bosentan REMS.
  • Do not distribute, transfer, loan, or sell product, except to certified dispensers.
  • Maintain records of compliance with REMS requirements.
  • Cooperate with audits carried out by the REMS program 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 the drug is distributed only to certified pharmacies.
  • Train all relevant staff involved in the distribution on the Bosentan REMS requirements.
At all times
  • Distribute only to certified pharmacies.
  • Maintain and submit records of drug distribution to the Bosentan Sponsors
  • Comply with audits carried out by the manufacturers, or a third party acting on behalf of the manufacturers 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.

Material Name Material Name Link
Outpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Outpatient Pharmacy Enrollment Form.pdf
Chain Pharmacy Headquarters Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Chain Pharmacy Headquarters Enrollment Form.pdf
Change in Reproductive Status and Pre-pubertal Annual Verification Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Change in Reproductive Status and Pre-pubertal Annual Verification Form.pdf
Fact Sheet (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Fact Sheet.pdf
Guide for Pateints (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Guide for Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Inpatient Pharmacy Enrollment Form.pdf
Pateint Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Patient Enrollment Form.pdf
Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Pharmacy Guide.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Prescriber Enrollment Form.pdf
Prescriber Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Prescriber Guide.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 REMS Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 REMS Full.pdf
REMS Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 REMS Website Screenshots.pdf
Testing and Patient Counseling Reporting Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Bosentan 2019 05 20 Testing and Patient Counseling Reporting Form.pdf

What updates have been made to the REMS?

Date Summary of change
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.

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