Approved Risk Evaluation and Mitigation Strategies (REMS)

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Opsumit (macitentan)
NDA #204410
REMS last update: 02/01/2019



What is the purpose of the REMS?

The goal of the Opsumit REMS Program is to mitigate the risk of embryo-fetal toxicity associated with Opsumit 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 Opsumit 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 Opsumit
  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 Opsumit must

To become certified to prescribe
  • Review the drug's Prescribing Information.
  • Review the following: Prescriber and Pharmacy Guide.
  • Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
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.
  • 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, and emergency contraception using the 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.
  • Enroll all female patients by completing and submitting the Patient Enrollment Form and submitting it to the REMS Program.
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
  • For pre-pubertal females at least age 8 years or older: Document reproductive status and submit to the REMS Program 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 her pregnancy test result.
At all times
  • For pre-pubertal females: Assess the patient's reproductive status.
  • Report pregnancies to Actelion Pharmaceuticals Ltd.
At all times; within 10 business days
  • Report a change or misclarification in reproductive status to the REMS Program using the Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form.

Females of reproductive potential who are prescribed Opsumit

Before treatment initiation
  • Review the 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.
  • 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.
  • 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 or healthcare provider who dispenses Opsumit 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 report a pregnancy immediately.
  • 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.
  • Agree to be contacted by the manufacturer 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 Opsumit

Before treatment initiation
  • Review the 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.
  • 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.
At all times
  • If over the age of 8: Be monitored for a change in reproductive status.
  • Inform the prescriber if there is change in reproductive status.

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

Before treatment initiation
  • Review the 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.
At all times
  • Inform the prescriber if there is a change in your reproductive status.

Outpatient Pharmacies that dispense Opsumit 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.
  • Train all relevant staff involved in dispensing on the Opsumit REMS Program requirements, procedures and REMS materials.
  • Establish processes and procedures to verify the female patient is enrolled, the reproductive status of the patient has not changed, and the prescriber is certified.
  • For females of reproductive potential: Establish processes and procedures to verify that pregnancy testing is complete or the prescriber authorized the refill.
Before dispensing
  • 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 inform the prescriber of a pregnancy immediately.
  • Verify the female patient is enrolled, the reproductive status has not changed, and the prescriber is certified through the processes and procedures established as a requirement of the REMS Program.
  • For females of reproductive potential: Verify that pregnancy testing is complete or the prescriber authorizes the refill through the processes and procedures established as a requirement of the REMS Program.
  • For females of reproductive potential: Dispense no more than a 30-days' supply.
At all times
  • Report pregnancies to Actelion Pharmaceuticals Ltd.
  • Not distribute, transfer, loan, or sell Opsumit, except to certified dispensers or prescribers.
  • For females of reproductive potential: Maintain and submit records of daily product dispensing data.
  • 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.

Inpatient Pharmacies that dispense Opsumit 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 enroll in the REMS Program by completing the Inpatient Pharmacy Enrollment Form and submitting it to the REMS Program.
  • Have the authorized representative review the Prescribing Information and the Prescriber and Pharmacy Guide.
  • Train all relevant staff involved in dispensing Opsumit 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 prengancy tests, and to inform the prescriber of a pregnancy immediately through the processes and procedures established as a requirement of the REMS Program.
At discharge
  • Dispense no more than a 15-day's supply.
At all times
  • Report pregnancies to Actelion Pharmaceuticals Ltd.
  • Not distribute, transfer, loan, or sell Opsumit, 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 Opsumit 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 Opsumit REMS Program requirement.
At all times
  • Distribute only to certified pharmacies.
  • Maintain records of drug distribution.
  • 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.

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 Opsumit 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/Opsumit_2019_02_01_Change_in_Reproductive_Potential_Status_and_Pre_Pubertal_Annual_Verification_Form.pdf
Guide for Female Patients (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Guide_for_Female_Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Inpatient_Pharmacy_Enrollment_Form.pdf
Patient Enrollment and Consent Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Patient_Enrollment_and_Consent_Form.pdf
Patient Enrollment and Consent Form for VA Use Only (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Patient_Enrollment_and_Consent_Form_for_VA_use_only.pdf
Prescriber and Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Prescriber_and_Pharmacy_Guide.pdf
Prescriber Enrollment and Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_Prescriber_Enrollment_and_Agreement_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_REMS_Full.pdf
REMS Program Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opsumit_2019_02_01_REMS_Program_Website_Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
02/01/2019 Modified to:
  1. Add provisions for prescribers to enroll patients in the Opsumit REMS online and by phone
  2. Add descriptions of the new patient enrollment processes in the REMS materials
  3. Add a description for the process of how prescribers and pharmacies enroll by phone in the REMS materials
  4. Add an option for prescribers to report a change in the patient's reproductive status by phone in the Opsumit REMS
10/16/2018

Modified:

  1. to reflect the revised Indication Statement
  2. the Guide for Females Who Can Get Pregnant to incorporate information on females who cannot get pregnant and retitle it as Guide for Female Patients
  3. the Prescriber and Pharmacy Guide and website to include the updated indication and updated language in the "Risk of teratogenicity" section to align with the updated labeling and incorporate content for females who cannot get pregnant from the Guide for Female Patients.
08/25/2017

Modified to:

  1. Clarify the reproductive status of females who had tubal sterilization as Female of Reproductive Potential (FRP).
  2. Remove non-REMS information and consent language from the patient enrollment forms.
  3. Clarifiy that re-enrollment of patients is not required by certified prescribers within the same practice.
  4. Make editorial changes and revisions throughout the Opsumit REMS to improve implementation of the REMS.
  5. Make editorial changes to the REMS website consistent with the redlined comments from the Agency's 8/1/17 comments.
03/21/2017 Modified to conform with revisions to the approved labeling for Opsumit (macitentan) in the Medication Guide.
02/22/2016 Modified to add a new Opsumit Patient Enrollment and Consent Form for VA Use Only.
11/17/2015 Modified to:

  1. Modify a statement to ensure that all certified outpatient pharmacies will be audited within 180 days after they are certified in the Opsumit REMS program in the REMS document.
  2. Make changes to clarify the roles and responsibilities of the inpatient and outpatient pharmacy authorized representatives in the REMS document.
  3. Change the title to “Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form” from the Reproductive Potential Status Form.
  4. Add a field (Reason for change in classification) to capture reasons for previous misclassification of reproductive status to the Reproductive Potential Status Form.
  5. Add a new female of non-reproductive potential subcategory (“Other medical reasons for permanent, irreversible infertility”) and update all relevant sections of the REMS document and related forms and Medication Guide to reflect this change.
10/18/2013 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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