Approved Risk Evaluation and Mitigation Strategies (REMS)

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Tracleer (bosentan)
NDA #209279 NDA #021290
REMS last update: 09/05/2017



What is the purpose of the REMS?

The goals of the Tracleer REMS are:

  1. To inform prescribers, patients, and pharmacists about the risks of Tracleer
  2. To minimize the risk of hepatotoxicity in patients who are exposed to Tracleer
  3. To minimize the risk of fetal exposures in female patients who are exposed to Tracleer
  4. To educate prescribers, patients, and pharmacies on the safe-use conditions for Tracleer

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 Tracleer must

To become certified to prescribe
  • Be able to determine whether a female is of reproductive potential as defined in the Prescriber and Pharmacy Guide for the Tracleer REMS program.
    | Prescriber and Pharmacy Guide |
  • Review the drug’s prescribing information.
  • Review the following educational materials: Prescriber and Pharmacy Guide for the Tracleer REMS program and Medication Guide.
    | Prescriber and Pharmacy Guide |
  • Enroll in the REMS by completing the Prescriber Enrollment and Agreement Form and submitting it to the REMS program.
    | Prescriber Enrollment and Agreement Form |
Before the first prescription
  • Counsel the patient that drug is only available through a restricted distribution program.
  • Provide the patient the Guide for Patients and Medication Guide.
    | Guide for Patients |
  • Assess the patient’s pretreatment liver function by ordering and reviewing a liver function test.
  • For a Female of Reproductive Potential (FRP): counsel the patient on the risk of teratogenicity, the need to use reliable contraception during treatment and for one month following treatment discontinuation, and her medical options in the event of unprotected sexual intercourse or known or suspected contraception failure.
  • For a FRP: counsel the patient to immediately contact her prescriber if the patient misses her period or suspects a pregnancy.
  • For a FRP: assess the patient’s pregnancy status by ordering and reviewing a pregnancy test.
  • For a Pre-Pubertal Female of Non-Reproductive Potential (FNRP): counsel the patient and/or patient guardian on the risk of teratogenicity.
  • For a FNRP: counsel the patient and/or patient guardian to immediately contact their prescriber if the patient begins to menstruate.
  • Enroll the patient by completing and submitting the appropriate Patient Enrollment and Consent Form to the REMS program.
    | Patient Enrollment and Consent Form | | Patient Enrollment and Consent Form (VA USE ONLY) |
Before each prescription after the first prescription
  • For a patient not complying with required testing: counsel the patient on program requirements.
Monthly during treatment
  • Assess the patient’s liver function by ordering and reviewing a liver function test.
  • For a FRP: assess the patient’s pregnancy status by ordering and reviewing a pregnancy test.
At least annually during treatment
One month after treatment discontinuation
  • For a FRP: assess the patient’s pregnancy status by ordering and reviewing a pregnancy test.
At all times

Females of Reproductive Potential (FRP) Patients who are prescribed Tracleer

Before the first prescription
During treatment
  • For females who can get pregnant: Use contraception as described in the Guide for Patients.
Monthly during treatment
  • Get a pregnancy test.
  • Receive counseling from the pharmacy on the need to use reliable contraception during treatment and for one month after stopping treatment.
One month after discontinuing
  • Get a pregnancy test and liver function test.
At all times
  • Immediately, inform the prescriber if the patient misses her period or suspects a pregnancy.

Pre-pubertal Females of Non-Reproductive Potential (FRNP) Patients and/or Patient Guardian who are prescribed Tracleer

Before the first prescription
Monthly during treatment
  • Get a liver function test.
At least annually during treatment
  • If 8 years or older, get evaluated for a change in reproductive status.
At all times
  • Inform the prescriber if the patient begins to menstruate.

Post-Menopausal Pre-pubertal Females of Non-Reproductive Potential (FNRP) Patients and Female Patients with other medical reason for permanent, irreversible infertility who are prescribed Tracleer

Before the first prescription
Monthly
  • Get a liver function test.

Male Patients who are prescriber Tracleer

Before the first prescription
Monthly
  • Get a liver function test.

Outpatient pharmacies that dispense Tracleer must

To become certified to dispense
  • Designate an authorized representative to carry out the certification process on behalf of the outpatient pharmacy.
  • Train all relevant staff involved in dispensing on the REMS program procedures and REMS materials.
  • Establish processes and procedures to verify that patient and prescriber enrollment forms are only received from the REMS program, prescriber is enrolled, and patient is enrolled.
Before dispensing
  • Counsel the patient on the risk of hepatoxicity and the need for monthly liver testing.
  • Provide the patient with a Medication Guide.
  • Verify that the liver function testing was completed by asking the patient or their prescriber.
  • For a female of reproductive potential (FRP): counsel the patient on the risk of serious birth defects and the need to use reliable contraception during treatment and for one month after stopping treatment.
  • For a FRP: counsel the patient on the need to complete a monthly pregnancy test and to inform her prescriber immediately if she suspects a pregnancy.
  • For a FRP: verify that the pregnancy test was completed by asking the patient. If the patient is unable to confirm, then ask the prescriber. If both the patient and prescriber are unable to confirm, then ask the prescriber to authorize a refill and remind the prescriber of obligation to order and review a monthly pregnancy test.
  • Obtain authorization to dispense by contacting the REMS coordinating center.
  • Dispense no more than a thirty days’ supply.
At all times
  • Report any adverse events, including hepatotoxicity, and any reports of pregnancy to the Manufacturer.
  • 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 Tracleer must

To become certified to dispense
  • Designate an authorized representative to carry out the certification process on behalf of the inpatient pharmacy.
  • Train all relevant staff involved in dispensing on REMS program requirements and REMS materials.
  • 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.
  • Have the authorized representative enroll in the REMS by completing the Inpatient Pharmacy Enrollment Form.
    | Inpatient Pharmacy Enrollment Form |
Before dispensing
  • Obtain authorization to dispense by contacting the REMS Program Coordinating Center.
Upon discharge
  • Dispense no more than a fifteen days’ supply.
At all times
  • Report any adverse events, including hepatotoxicity, and any reports of pregnancy to the Manufacturer.
  • 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.

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 Tracleer REMS, see the DailyMed link(s).
Material Name Material Name Link
Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Change_in_Reproductive_Potential_Status_and_Pre_Pubertal_Annual_Verification_Form.pdf
Guide for Patients (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Guide_for_Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Inpatient_Pharmacy_Enrollment_Form.pdf
Patient Enrollment and Consent Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Patient_Enrollment_and_Consent_Form.pdf
Patient Enrollment and Consent Form (VA USE ONLY) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Patient_Enrollment_and_Consent_Form_VA_USE_ONLY.pdf
Prescriber and Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Prescriber_and_Pharmacy_Guide.pdf
Prescriber Enrollment and Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Prescriber_Enrollment_and_Agreement_Form.pdf
REMS document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_REMS_Document.pdf
REMS full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_Full.pdf
REMS Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tracleer_2017-09-05_REMS_Website_Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
09/05/2017 Modified to change the Tracleer REMS Document to add an additional NDA number and remove the reference to the Dear Healthcare Provider Letter, as well as changes to the REMS website and materials that update the indication to include pediatric patients.
12/16/2016 Modified to:

  1. Add a new form for Veterans Affairs use, Tracleer Patient Enrollment and Consent Form – for VA Use
  2. Update the patient consent language and remove non- REMS information in the Patient Enrollment and Consent Form.
  3. Update these enrollment forms in the Dear Healthcare Provider Letter, Prescriber and Pharmacy Guide REMS Document, and on the REMS website.
12/04/2015 Modified to:

  1. Change the REMS program name to “the Tracleer REMS Program” from “Tracleer Access Program”.
  2. Replace the "Tracleer Renewal Form" with the "Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form".
  3. Replace the Hospital Certification with Inpatient Pharmacy Certification and add the Inpatient Pharmacy Enrollment Form.
  4. Change the roles and responsibilities of the inpatient and outpatient pharmacy authorized representatives.
  5. Remove the monthly wallet reminder card.
  6. Remove form FRM-549-COP-US that was required for patients to receive Tracleer when traveling outside of the United States.
  7. Add a new female of non-reproductive potential subcategory (“Other medical reasons for permanent, irreversible infertility”) to all relevant sections of the REMS document and related forms
07/01/2013 Modified to:

  1. Replace “systemic-to-pulmonary” with “heart disease with left-to-right” in the Prescribers Essentials Guide, Dear Prescriber Letter, Prescriber Retraining Letter, and Dear Hospital Letter.
  2. Move the statement, "Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary edema occur, consider the diagnosis of associated PVOD and consider discontinuing Tracleer (5.5)", from the 5th position to the 3rd position to match the order of the Warnings and Precautions in the Prescribers Essentials Guide.
  3. Make updates to the REMS Website.
10/02/2012 Modified to:

  1. Add requirements for use of Tracleer in an inpatient setting, including prescriber certification, hospital certification, and a description of how inpatient settings will obtain the drug.
  2. Differentiate between inpatient and outpatient dispensing processes.
  3. Communicate the availability of a hospital blister in the REMS New Dear Healthcare Provider letters for prescribers and hospitals, within 60 days of approval of the modified REMS.
  4. Change the implementation system to include certified hospitals and plans to monitor compliance with the Tracleer REMS requirements.
  5. add an initial enrollment form and an annual re-enrollment form change various appended REMS materials including the patient enrollment form
  6. make clarifications to the revised processess in the various appended REMS materials including: the patient enrollment form, to consist of an initial enrollment form and an annual re-enrollment form; the Prescriber Essentials guide; Patient Essentials guide; monthly reminder for patients; new hospital use communication material; and Tracleer REMS website landing page.
02/19/2010 Modified to modify the timetable for submission of assessments.
08/07/2009 Approval 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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