Approved Risk Evaluation and Mitigation Strategies (REMS)

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Ambrisentan Shared System
Shared System REMS
REMS last update: 03/28/2019

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Letairis (ambrisentan) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 022081 GILEAD 05/29/2009 725d4e73-6c83-477a-adc6-0ae4a133a844 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=022081
ambrisentan (Info at Drugs@FDA) ANDA 210784 SUN PHARM 03/28/2019
ambrisentan (Info at Drugs@FDA) ANDA 208252 WATSON LABS INC 03/28/2019
ambrisentan (Info at Drugs@FDA) ANDA 208441 MYLAN 03/28/2019
ambrisentan (Info at Drugs@FDA) ANDA 209509 PAR PHARM INC 04/10/2019
ambrisentan (Info at Drugs@FDA) ANDA 208354 SIGMAPHARM LABS LLC 04/10/2019

What is the purpose of the REMS?

The goal of the Ambrisentan REMS Program is to mitigate the risk of embryo-fetal toxicity associated with ambrisentan 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 Ambrisentan 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 ambrisentan
  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 ambrisentan 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) 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: Counsel the patient on the risk of embryo-fetal toxicity, the need to use highly reliable contraception during treatment and for one month following treatment discontinuation, and emergency contraception 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 using the Guide for Female Patients.
  • Enroll all female patients by completing 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 the required testing or if she is not using appropriate contraception.
  • 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 or older: Document reproductive status and submit to the REMS Program using Change in Reproductive Potential Status and Pre-Pubertal Annual Verification Form.
After treatment discontinuation; for 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 Program.
At all times, within 10 business days
  • Report a change or misclassification in reproductive status to the REMSProgram using the Change in Reproductive Potential Status and Pre-Pubertal Annual Verification Form.

Females of reproductive potential who are prescribed ambrisentan:

Before treatment initiation
  • Review the Guide for Female Patients.
  • Get a pregnancy test.
  • 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 the need to use highly reliable contraception during treatment and for one month following treatment discontinuation, and emergency contraception using the Guide for Female Patients.
During treatment;before dispensing
  • Receive counseling from the pharmacy or healthcare provider who dispenses ambrisentan on the risk of embryo-fetal toxicity, the need to use highly reliable contraception during treatment and for one month following treatment discontinuation, emergency contraception, 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 highly reliable contraception as described in the Guide for Female Patients.
After treatment discontinuation; one month
  • Get a pregnancy test.

Pre-pubertal females who are prescribed ambrisentan:

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 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 a change in your reproductive status

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

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 and healthcare providers that dispense ambrisentan must:

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the Ambrisentan REMS on behalf of the pharmacy.
  • Have the authorized representative review the Prescriber and Pharmacy Guide.
  • Have the authorized representative enroll in the Ambrisentan REMS by completing the Outpatient Pharmacy Enrollment Formand submitting it to the Ambrisentan REMS.
  • Train all relevant staff involved in dispensing ambrisentan on the Ambrisentan REMS requirements using the Prescriber and Pharmacy Guide.
  • Ensure the pharmacy is able to support electronic data exchanges and communications with the Ambrisentan REMS.
  • Establish processes and procedures to verify the patient’s prescriber is enrolled for all patients and if the patient is female, verify the patient is enrolled and the reproductive status of the patient has not changed.
  • For females of reproductive potential: Establish processes and procedures to verify that pregnancy testing is completed or the prescriber authorizes the refill.
Before dispensing
  • For females of reproductive potential: Counsel the patient on the risk of embryo-fetal toxicity, the need to use highly reliable contraception and emergency contraception, to get monthly pregnancy tests, and inform the prescriber of a pregnancy immediately.
  • Verify with the Ambrisentan REMS that the patient’s prescriber is enrolled for all patients and if the patient is female, verify the patient is enrolled and the reproductive status has not changed.
  • For females of reproductive potential: Verify that the pregnancy testing is complete or the prescriber authorizes the refill
  • For females of reproductive potential, dispense no more than a 30 days’ supply.
At all times
  • Report adverse events and reports of pregnancies to the Ambrisentan REMS.
  • Report a change or misclassification in reproductive status to the Ambrisentan REMS.
  • Do not distribute, transfer, loan, or sell ambrisentan, except to certified dispensers.
  • Maintain and submit records of daily product dispensing data for female patients to the Ambrisentan REMS.
  • 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 ambrisentan must:

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the Ambrisentan REMS on behalf of the pharmacy
  • Have the authorized representative review the Prescriber and Pharmacy Guide.
  • Have the authorized representative enroll in the Ambrisentan REMS by completing Inpatient Pharmacy Enrollment Formand submitting it to the Ambrisentan REMS.
  • Train all relevant staff involved in dispensing ambrisentan on the Ambrisentan REMS requirements using the Prescriber and Pharmacy Guide.
  • Establish processes and procedures to verify the female patient is enrolled or will be enrolled in the REMS Program prior to discharge, her reproductive status, and the female patient is under the supervision and care of a certified prescriber. Enrolled.
  • 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 with the Ambrisentan REMS that the patient’s prescriber is enrolled for all patients and if the patient is female verify the patient is enrolled.
  • For females of reproductive potential: Verify that the patient has been counseled on the risk of embryo-fetal toxicity and pregnancy testing is complete.
At discharge
  • Dispense no more than a 15 days’ supply.
At all times
  • Report any adverse events and reports of pregnancies to the Ambrisentan REMS.
  • Report a change or misclassification in reproductive status to the Ambrisentan REMS.
  • Do not distribute, transfer, loan, or sell ambrisentan, except to certified dispensers.
  • 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.

Wholesalers that distribute ambrisentan 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 Ambrisentan REMS requirements.
At all times
  • Distribute only to certified pharmacies.
  • Maintain and submit records of drug distribution to the Ambrisentan REMS.
  • 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 Ambrisentan Shared System 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/Ambrisentan Shared System 2019 03 28 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/Ambrisentan Shared System 2019 03 28 Guide for Female Patients.pdf
Inpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 Inpatient Pharmacy Enrollment Form.pdf
Outpatient Pharmacy Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 Outpatient Pharmacy Enrollment Form.pdf
Patient Enrollment and Consent Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 Patient Enrollment and Consent Form.pdf
Prescriber and Pharmacy Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 Prescriber and Pharmacy Guide.pdf
Prescriber Enrollment and Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 Prescriber Enrollment and Agreement Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 REMS Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 REMS Full.pdf
Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Ambrisentan Shared System 2019 03 28 Website Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
03/28/2019 Modified to establish a Single Shared System (SSS) REMS for the elements to assure safe use and the implementation system required for the reference listed drug (RLD) Letairis and ANDAs referencing Letairis, called the Ambrisentan REMS Program.
11/30/2018 Modified to update the Prescriber Guide to conform with the PLLR conversion and retitle Guide for Females Who Can Get Pregnant to Guide for Female Patients. The Medication Guide is no longer necessary as an element of the approved REMS but will continue to be part of the approved labeling.
09/27/2017 Modified to add an online enrollment option for patient and prescriber enrollment.
07/21/2017 Modified to update the Letairis REMS Patient Enrollment and Consent Form.
12/15/2016 Modified to update the following REMS document and materials including the Letairis REMS; Supporting Document, Prescriber Enrollment and Agreement Form, Prescriber Guide to the Letairis REMS Program, Program Guide for Females Who Can Get Pregnant, Patient Enrollment and Consent Form, Website.
10/02/2015 Modified to incorporate the revised indication into the REMS appended material, Prescriber Guide for the Letairis REMS Program.
10/29/2014 Modified to:

  1. Clarify the change in classification categories by changing the name of the Reproductive Potential Status Form to the Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form.
  2. Change the definition of females of non-reproductive potential (FNRP) in the REMS Document, the Reproductive Potential Status and Pre-pubertal Annual Verification Form, Prescriber Guide for the Letairis REMS Program, and the Letairis REMS Program Guide for Females Who Can Get Pregnant and REMS website.
  3. Communicate that Gilead is paying pharmacies for health information in order to conduct the REMS program in the Patient Enrollment and Consent Form.
01/31/2014 Modified to align the contraceptive information in these appended REMS materials with the acceptable contraceptive options that are listed in the package insert made revisions to the Prescriber Guide for the Letairis REMS Program and the Letairis REMS Program Guide for Females Who Can Get Pregnant.
08/17/2013 Modified to:

  1. Conform to the content of the labeling changes made revisions to the Medication Guide and revisions to relevant sections of the appended REMS materials.
  2. Eliminate enrollment of males in the REMS program.
  3. Revise the requirements applicable to females (females of reproductive potential and females of non-reproductive potential).
10/19/2012 Modified to align the content with the above referenced labeling changes made revisions to the Medication Guide and revisions to relevant sections of the appended REMS materials, specifically, the REMS website
02/15/2012 Modified to align the content with the above referenced labeling changes made revisions to the Medication Guide and revisions to the relevant sections of the REMS document and appended REMS materials, specifically, the Prescriber Guide: Letairis and LEAP Program, and Patient Enrollment Guide.
03/03/2011 Modified to align the content with the above referenced labeling changes made revisions to the Medication Guide and revisions to the relevant sections of the REMS document and appended REMS materials, specifically, the Prescriber Guide: Letairis and LEAP Program, and Patient Enrollment Guide.
10/13/2010 Modified to align with labeling changes made revisions to the Medication Guide and revisions to relevant section of the REMS materials, specifically, the Prescriber Educational Brochure, Patient Enrollment Guide, and Patient Educational Brochure.
08/24/2010 Modified to revise the timetable for submission of assessments.
08/05/2009 Modified to align with labeling changes made revisions to the REMS Prescriber Enrollment Guide, Patient Enrollment Guide (For starting therapy with Letairis) and Patient Education Brochure (Letairis therapy: What you need to know).
07/01/2009 Modified to align with labeling changes made revisions to the REMS Prescriber Education Brochure and the REMS Patient Education Brochure (Letairis Therapy: What You Need to Know).
05/29/2009 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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