Approved Risk Evaluation and Mitigation Strategies (REMS)

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Adempas (riociguat)
NDA #204819
REMS last update: 12/06/2018



What is the purpose of the REMS?

The goal of the Adempas REMS Program is to mitigate the risk of embryo-fetal toxicity associated with Adempas by:

  1. Ensuring prescribers are educated on the following:
    • the risk of embryo-fetal toxicity
  2. Ensuring prescribers are educated on and adhere to the following:
    • counseling patients about the risk and the need for monthly monitoring
    • enrolling patients in the Adempas REMS Program
    • monitoring patients at baseline and monthly
  3. Ensuring that pharmacies are educated on the following:
    • the risk 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 Adempas
  5. Ensuring that patients are informed about:
    • the risk 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 Adempas 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 and Agreement 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 and Consent Form.
  • For all females: Counsel the patient that the drug is only available through a restricted distribution program.
  • For females of reproductive potential: Counsel the patient on the risk of embryo-fetal toxicity, the need to use effective contraception during treatment and for one month following treatment discontinuation, emergency contraception, and to immediately contact her prescriber if she misses a menstrual period or suspects that she is pregnant using the Guide for Female Patients.
  • For females of reproductive potential: Assess the patient's pregnancy status by ordering and reviewing her pregnancy test result.
  • 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 and Consent 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 the required testing or if she is not using effective contraception, and to immediately 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 Bayer HealthCare Pharmaceuticals, Inc.
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 Verification Form.

Females of reproductive potential who are prescribed Adempas:

Before treatment initiation
  • Review the Guide for Female Patients.
  • Get a pregnancy test.
  • Enroll in the REMS Program by completing the Patient Enrollment and Consent 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 effective contraception during treatment and for one month following treatment discontinuation, emergency contraception, and to immediately contact her prescriber if she misses a menstrual period or suspects that she is pregnant using the Guide for Female Patients.
  • Adhere to the safe use condition: Communicate with the pharmacy to confirm completion of pregnancy testing.
Before dispensing
  • Receive counseling from the pharmacy or the prescriber who dispenses Adempas on the risk of embryo-fetal toxicity, the need for effective 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 effective 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 Adempas:

Before treatment initiation
  • Review the Guide for Female Patients.
  • Enroll in the REMS Program by completing the Patient Enrollment and Consent 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 immediately 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 Adempas:

Before treatment initiation
  • Review the Guide for Female Patients.
  • Enroll in the REMS Program by completing the Patient Enrollment and Consent 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 and prescribers that dispense Adempas must:

To become certified to dispense
  • For outpatient pharmacies: 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.
  • For prescribers who dispense: Complete the certified dispenser section of the Prescriber Enrollment and Agreement Form.
  • Review the Prescriber and Pharmacy Guide.
  • Train all relevant staff involved in dispensing on the Adempas REMS Program requirements, procedures, and REMS materials using the Prescriber and Pharmacy Guide.
  • Establish processes and procedures to verify the female patient is enrolled, the reproductive status of the patient has not changed, the prescriber is certified, and if the prescriber dispensed a 30 days' supply of Adempas.
  • For females of reproductive potential: Establish processes and procedures to verify that pregnancy testing is complete or the prescriber authorized the refill through the processes and procedures established as a requirement of the REMS Program.
Before dispensing
  • For females of reproductive potential: Counsel the patient on the risk of embryo-fetal toxicity, the need to use effective contraception during treatment and for one month after stopping treatment, to get monthly pregnancy tests, and inform her prescriber immediately if she misses a menstrual period or suspects she may be pregnant.
  • Verify the female patient is enrolled, the reproductive status has not changed, the prescriber is certified, and if the prescriber dispensed a 30 days' supply of Adempas 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.
  • For prescribers who dispense: Report dispensing Adempas to the REMS Program using the Patient Enrollment and Consent Form.
At all times
  • Report pregnancies to Bayer HealthCare Pharmaceuticals, Inc.
  • Not distribute, transfer, loan, or sell Adempas.
  • For outpatient pharmacies: Maintain and submit records of daily product dispensing data for females of reproductive potential.
  • Maintain records of all processes and procedures including compliance with those processes and procedures.
  • 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 Adempas 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 Prescriber and Pharmacy Guide.
  • Train all relevant staff involved in dispensing Adempas on the REMS Program Requirements, procedures and REMS materials using the Prescriber and Pharmacy Guide.
  • 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 effective 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, her reproductive status, 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 pregnancy testing is complete, and that the patient is counseled on the risk of embryo-fetal toxicity, the need to use effective 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.
At discharge
  • Verify female patient is enrolled in the REMS Program through the processes and procedures established as a requirement of the REMS.
  • Dispense no more than a 15-day's supply.
At all times
  • Report pregnancies to Bayer HealthCare Pharmaceuticals, Inc.
  • Not distribute, transfer, loan, or sell Adampas.
  • Maintain records of all processes and procedures including compliance with those processes and procedures.
  • 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 Adempas must:

To be able to distribute
  • Establish processes and procedures to ensure that the drug is distributed only to certified pharmacies and certified prescribers who can dispense Adempas.
  • Train all relevant staff involved in distribution on the Adempas REMS Program Requirement.
At all times
  • Distribute only to certified pharmacies and certified prescribers who can dispense Adempas.
  • 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 Adempas 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/Adempas_2018_12_06_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/Adempas_2018_12_06_Guide_for_Female_Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_Inpatient_Pharmacy_Enrollment_Form.pdf
Patient Enrollment and Consent Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_Patient_Enrollment_and_Consent_Form.pdf
Prescriber and Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_Prescriber_and_Pharmacy_Guide.pdf
Prescriber Enrollment and Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_Prescriber_Enrollment_and_Agreement_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_REMS_Full.pdf
REMS Program Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Adempas_2018_12_06_REMS_Program_Website_Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
12/06/2018 Modified to:

  1. Accommodate for certified prescribers’ dispensing of Adempas to new patients. This modification results in changes to the following:
    • REMS document
    • Prescriber Enrollment Form
    • Patient Enrollment Form
    • Prescriber and Pharmacy Guide
  2. Reflect an update to the REMS document to correspond to the current format
  3. Update 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
  4. Reflect editorial changes throughout to replace "teratogenicity" with "embryo-fetal toxicity" and replace "reliable" with "effective"
  5. Update the presentation of the REMS goals to better articulate how the REMS is structured to mitigate the risk
  6. Remove the Medication Guide as an element of the approved REMS (The Medication Guide will still be maintained as part of the approved labeling)
01/17/2017 Modified to include information regarding idiopathic hypertension and switching from a PDE5 inhibitor to Adempas and vice versa in the Medication Guide.
10/04/2016 Modified to:

  1. Remove non-REMS related information from the Adempas REMS Patient Enrollment and Consent Form eliminate the VA REMS Patient Enrollment and Consent Form
  2. Add the word “REMS” to the title of the following forms: Adempas REMS Patient Enrollment and Consent Form and Adempas REMS Patient Enrollment and Consent Form
12/04/2015 Modified to:

  1. Modify a statement to ensure all certified outpatient pharmacies are audited within 180 days after they are certified in the Adempas 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 in 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 to reflect this change.
06/11/2014 Modified to:

  1. Update the REMS website to include links to Spanish versions of the Medication Guide and the REMS Guide for Females Who Can Get Pregnant.
  2. Make a logo change to add tablet dose availability just below the words “Adempas” and “riociguat tablets”.
  3. Update the REMS website so that when one clicks on the Patient Information Tab, the important safety information (ISI) for the patient appears.
  4. Make administrative changes to the Veteran’s Administration (VA) Adempas Patient Enrollment and Consent Form.
10/08/2013 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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