Approved Risk Evaluation and Mitigation Strategies (REMS)

Macitentan
Shared System REMS
REMS last update: 04/06/2021

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Opsumit (Macitentan) (Info at Drugs@FDA) NDA 204410 ACTELION 04/06/2021
Macitentan (Info at Drugs@FDA) ANDA 211224 ZYDUS 04/06/2021

What is the purpose of the REMS?

The goal of the Macitentan REMS Program is to mitigate the risk of embryo-fetal toxicity associated with macitentan by:
  1. Ensuring prescribers are educated on the following:
    • the risks of 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 Macitentan REMS Program
    • monitoring patients at baseline and monthly
  3. Ensuring that pharmacies are educated on the following:
    • the risks of 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 macitentan
  5. Ensuring that patients are informed about:
    • the risks of 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 macitentan must:

To become certified to prescribe
Before treatment initiation (first dose)
  • For all females: Assess the patient's reproductive status using the definitions in the Prescriber and Pharmacy Guide. Document and submit the results to the REMS Program using the Patient Enrollment Form. | Prescriber and Pharmacy Guide | | Patient Enrollment Form |
  • For all females: Counsel the patient that the drug is only available through a restricted distribution program.
  • For females of reproductive potential: Assess the patient’s pregnancy status by ordering and reviewing her pregnancy test result.
  • 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 following treatment discontinuation, and emergency contraception using the Guide for Female Patients. | Guide for Female Patients |
  • For pre-pubertal females: Counsel the patient on the risk of embryo-fetal toxicity and to immediately contact her prescriber if she begins to menstruate using the Guide for Female Patients. | Guide for Female Patients |
  • Enroll all female patients by completing and submitting the Patient Enrollment Form and submitting it to the REMS Program. | Patient Enrollment Form |
During treatment; before each prescription
  • For females of reproductive potential: Counsel the patient if she is not complying with required testing, if she is not using appropriate contraception, and to contact her prescriber if she misses a menstrual period or suspects that she is pregnant.
  • For females of reproductive potential: Assess the patient's pregnancy status by ordering and reviewing her pregnancy test result.
During treatment; at least annually
After treatment discontinuation; one month
  • For females of reproductive potential: Assess the patient's pregnancy status by ordering and reviewing her pregnancy test result.
At all times
  • For pre-pubertal females: Assess the patient’s reproductive status.
  • Report pregnancies to the REMS Coordinating Center.
At all times; within 10 business days

Females of reproductive potential who are prescribed macitentan

Before treatment initiation
  • Review the Guide for Female Patients. | Guide for Female Patients |
  • Get a pregnancy 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 embryo-fetal toxicity, the need to use reliable contraception, and emergency contraception using the Guide for Female Patients. | Guide for Female Patients |
  • Adhere to the safe use condition: Communicate with the pharmacy to confirm completion of pregnancy testing.
During treatment; before each dispensing
  • Receive counseling from the pharmacy on the risk of embryo-fetal toxicity, the need for reliable contraception during treatment and for one month after stopping treatment, to get monthly pregnancy tests, and to immediately contact her prescriber if she misses a menstrual period or suspects she is pregnant.
  • Get a pregnancy test.
  • Adhere to the safe use condition: Communicate with the pharmacy to confirm completion of pregnancy 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 Female Patients. | Guide for Female Patients |
  • Agree to be contacted by the REMS Coordinating Center if you become pregnant.
After treatment discontinuation; one month
  • Get a pregnancy test.
At all times
  • Inform the prescriber immediately if you miss a menstrual period or suspect a pregnancy.

Pre-pubertal females who are prescribed macitentan:

Before treatment initiation
  • Review the Guide for Female Patients. | Guide for Female Patients |
  • Enroll in the REMS Program 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 embryo-fetal toxicity and to contact your prescriber if you begin to menstruate using the Guide for Female Patients. | Guide for Female Patients |
At all times
  • If over the age of 8: Be monitored for a change in reproductive status.
  • Inform the prescriber if there is a change in reproductive status.

Post-menopausal females or females with other medical reason for permanent, irreversible infertility who are prescribed macitentan:

Before treatment initiation
  • Review the Guide for Female Patients. | Guide for Female Patients |
  • Enroll in the REMS Program by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program. | Patient Enrollment Form |
At all times
  • Inform the prescriber if there is a change in your reproductive status.

Outpatient Pharmacies that dispense macitentan 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 Prescribing Information and the Prescriber and Pharmacy Guide. | Prescriber and Pharmacy Guide |
  • Have the authorized representative enroll in the REMS Program by completing the Outpatient Pharmacy Enrollment Form and submitting it to the REMS Program. | Outpatient Pharmacy Enrollment Form |
  • Train all relevant staff involved in dispensing on the Macitentan REMS requirements, procedures, and REMS materials.
Before dispensing
  • Obtain authorization to dispense each prescription by contacting the REMS Program to verify female patients are enrolled, the reproductive status has not changed, the prescriber is certified, and pregnancy test is completed for females of reproductive potential or the prescriber authorizes the refill.
  • 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, to get monthly pregnancy tests, and to inform the prescriber immediately if she misses a menstrual period or suspects she is pregnant.
  • For females of reproductive potential: Dispense no more than a 30-days' supply.
To maintain certification to dispense
  • Have a new authorized representative enroll in the REMS Program by completing the Outpatient Pharmacy Enrollment Form if the authorized representative changes. | Outpatient Pharmacy Enrollment Form |
At all times
  • Report pregnancies to the REMS Coordinating Center.
  • Not distribute, transfer, loan, or sell macitentan, except to certified dispensers.
  • For all females: Maintain and submit records of daily product dispensing data.
  • Maintain records that all processes and procedures are in place and are being followed.
  • 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.

Inpatient Pharmacies that dispense macitentan 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 pharmacy.
  • Have the authorized representative review the Prescribing Information and the Prescriber and Pharmacy Guide. | Prescriber and Pharmacy Guide |
  • Have the authorized representative enroll in the REMS Program by completing the Inpatient Pharmacy Enrollment Form and submitting it to the REMS Program. | Inpatient Pharmacy Enrollment Form |
  • Train all relevant staff involved in dispensing macitentan on the REMS Program requirements, procedures, and REMS materials.
  • Establish processes and procedures to verify the female patient is enrolled in the REMS program or will be enrolled prior to discharge, her reproductive status, and the female patient is under the supervision and care of a certified prescriber.
  • For females of reproductive potential: establish processes and procedures to verify pregnancy testing is complete, and that the patient is counseled on the risk of embryo-fetal toxicity, the need to use reliable contraception, to get monthly pregnancy tests, and to inform the prescriber of a pregnancy immediately.
Before dispensing
  • Verify the female patient is under the supervision and care of a certified prescriber, and that she is enrolled or will be enrolled in the REMS Program prior to discharge through the processes and procedures established as a requirement of the REMS Program.
  • For females of reproductive potential: Verify the pregnancy testing is complete, and that the patient is counseled on the risk of embryo-fetal toxicity, the need to use reliable contraception, to get monthly pregnancy tests, and to inform the prescriber of a pregnancy immediately through the processes and procedures established as a requirement of the REMS Program.
To maintain certification to dispense
  • Have a new authorized representative enroll in the REMS Program by completing the Inpatient Pharmacy Enrollment Form if the authorized representative changes. | Inpatient Pharmacy Enrollment Form |
At discharge
  • Dispense no more than a 15-days' supply.
At all times
  • Report pregnancies to the REMS Coordinating Center.
  • Not distribute, transfer, loan, or sell macitentan, except to certified dispensers.
  • Maintain records that all processes and procedures are in place and are being followed.
  • Comply with audits carried out by the manufacturer or a third party acting on behalf of the manufacturer to ensure that all processes and procedures are in place and are being followed.

Wholesalers-distributors that distribute macitentan 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 distribution on the Macitentan REMS requirement.
At all times
  • Distribute only to certified pharmacies.
  • Maintain and submit records of monthly drug distribution for all macitentan shipments.
  • 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 Macitentan REMS, see the DailyMed link on the Products tab.

Material Name Material Name Link
Change in Reproductive Status and Pre-pubertal Annual Verification Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Change_in_Reproductive_Status_and_Pre-pubertal_Annual_Verification_Form.pdf
Guide for Female Patients (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Guide_for_Female_Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Inpatient_Pharmacy_Enrollment_Form.pdf
Outpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Outpatient_Pharmacy_Enrollment_Form.pdf
Patient Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Patient_Enrollment_Form.pdf
Patient Enrollment Form for VA use only (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Patient_Enrollment_Form_for_VA_use_only.pdf
Prescriber and Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Prescriber_and_Pharmacy_Guide.pdf
Prescriber Enrollment and Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_Prescriber_Enrollment_and_Agreement_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_REMS_Full.pdf
REMS Program Website (www.MacitentanREMSProgram.com) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Macitentan_2021_04_06_REMS_Program_website_(www.MacitentanREMSProgram.com).pdf

What updates have been made to the REMS?

Date Summary of change
04/06/2021 Approval of the Shared System 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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