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The goals of the isotretinoin risk evaluation and mitigation strategy are:
To prevent fetal exposure to isotretinoin
To inform prescribers, pharmacists, and patients about isotretinoin’s serious risks and safe use conditions
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.
For patients who can become pregnant: Assess the patient’s
pregnancy status by ordering and confirming an initial negative
pregnancy test result. Document and submit the result to the
REMS Program using the Patient Enrollment Form for Patients
Who Can Get Pregnant.
| Patient Enrollment Form for Patients Who Can Get Pregnant |
Before treatment initiation (first
dose); at least 19 days after the
first pregnancy test and in the first 5 days of the menstrual
period and immediately before
treatment
For patients who can become pregnant who have regular
menstrual cycles: Assess the patient’s pregnancy status by
ordering and confirming a second negative, CLIA-certified pregnancy test result. Document and submit the result to the
REMS Program.
Before treatment initiation (first
dose); at least 19 days after the
first pregnancy test and
immediately before treatment
For patients who can become pregnant who have amenorrhea,
irregular cycles, or use contraceptives that preclude withdrawal
bleeding: Assess the patient’s pregnancy status by ordering and
confirming a second, negative, CLIA-certified pregnancy test
result. Document and submit the result to the REMS Program.
During treatment; before each
prescription
Assess the patient’s current reproductive status.
For patients who cannot become pregnant: Counsel the patient on
the risks of isotretinoin using the Fact Sheet. Document and
submit confirmation of counseling to the REMS.
| Fact Sheet |
For patients who can become pregnant: Counsel the patient on
the risks of isotretinoin and program requirements using the
Guide for Patients Who Can Get Pregnant and Contraception
Counseling Guide. Document and submit confirmation of
counseling to the REMS Program.
| Contraception Counseling Guide |
| Guide for Patients Who Can Get Pregnant |
For patients who can become pregnant: Document and submit the
patient’s contraception to the REMS Program.
During treatment, on the date
of the last dose
For patients who can become pregnant: Assess the patient’s
pregnancy status by ordering and reviewing a CLIA-certified
pregnancy test. Document and submit the results to the REMS
Program.
After treatment discontinuation,
30 days after the date of the
last dose
For patients who can become pregnant: Assess the patient’s
pregnancy status by ordering and reviewing a CLIA-certified
pregnancy test. Document and submit the results to the REMS
Program.
Re-activate in the REMS Program by completing the reactivation.
At all times
Prescribe no more than a 30 days’ supply
Not prescribe refills
Report pregnancies to the REMS Program.
During treatment, within 7 days
before each prescription
For patients who can become pregnant: Assess the patient’s
pregnancy status by ordering and reviewing a CLIA-certified
pregnancy test. Document and submit the results to the REMS
Program.
Re-activate in the REMS Program by completing the reactivation.
Patients who can become pregnant who are prescribed isotretinoin:
Before treatment initiation, for
30 days
Adhere to the safe use condition: use contraception and not get
pregnant as described in the Guide for Patients Who Can Get
Pregnant.
| Guide for Patients Who Can Get Pregnant |
Before treatment initiation
Receive counseling from the prescriber on the risks of isotretinoin
and the REMS program requirements.
Receive counseling from the prescriber or another expert on the
contraception requirements.
Enroll in the REMS Program by completing the Patient Enrollment
Form for Patients Who Can Get Pregnant with the prescriber.
Enrollment information will be provided to the REMS Program.
| Patient Enrollment Form for Patients Who Can Get Pregnant |
Get two pregnancy tests as directed by your prescriber.
During treatment; before each
prescription
Receive counseling on the risks of isotretinoin and the REMS
program requirements.
Get a pregnancy test as directed by your prescriber.
During treatment, within 7 days
of the last pregnancy test
Get your isotretinoin from the pharmacy.
During treatment and after
treatment discontinuation; for
30 days
Adhere to safe use conditions: Use contraception as described in
the Guide for Patients Who Can Get Pregnant; not take
isotretinoin if pregnant, breastfeeding, or not using contraception;
not get pregnant; and not donate blood.
| Guide for Patients Who Can Get Pregnant |
At all times
Inform the prescriber if you become pregnant.
Adhere to safe use conditions: Not share isotretinoin.
Patients who cannot become pregnant who are prescribed isotretinoin:
Before treatment initiation
Receive counseling from the prescriber on the risk of isotretinoin
and the program requirements.
Enroll in the REMS Program by completing the Patient Enrollment
Form for Patients Who Cannot Get Pregnant with the prescriber.
Enrollment information will be provided to the REMS Program.
| Patient Enrollment Form for Patients Who Cannot Get Pregnant |
During treatment; before each
prescription
Receive counseling on the risks of isotretinoin and the program
requirements.
During treatment; within 30
days of your last office visit
Get your isotretinoin from the pharmacy.
During treatment and after
treatment discontinuation; for
30 days
Adhere to safe use conditions: Not donate blood.
At all times
Adhere to safe use conditions: Not share isotretinoin.
Pharmacies that dispense isotretinoin 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 Pharmacist Guide.
| Pharmacist Guide |
Have the authorized representative enroll in the REMS Program by
completing the Pharmacy Enrollment Form and submitting it to
the REMS Program.
| Pharmacy Enrollment Form |
Train all relevant staff involved in dispensing using the Pharmacist
Guide.
| Pharmacist Guide |
Establish processes and procedures to document the authorization
number for each prescription.
Establish processes and procedures to not dispense an isotretinoin
prescription after the date provided by the REMS Program, and to
reverse the authorization to dispense the prescription if needed,
and steps to return isotretinoin to inventory.
Before dispensing
Obtain authorization to dispense each prescription by contacting
the REMS Program to verify the prescriber is certified, the patient
is enrolled, the patient counseling is complete, and dispensing is
within the designated timeframe. For patients who can become
pregnant: the patient is not pregnant, the patient’s contraception
is confirmed, and the patient’s monthly comprehension questions
are complete.
Document the authorization number for each prescription through
the processes and procedures established as a requirement of the
REMS Program.
To maintain certification to
dispense, annual
Have the authorized representative re-enroll in the REMS
Program.
At all times
Not dispense more than a 30 days’ supply.
Not dispense refills.
Not dispense after the date provided by the REMS Program,
reverse the authorization to dispense, and return isotretinoin to
inventory through the processes and procedures established as a
requirement of the REMS program.
Return unused product to the manufacturer.
Not distribute, transfer, loan, or sell isotretinoin.
Comply with audits carried out by the Isotretinoin Applicants, or a
third party acting on behalf of the Isotretinoin Applicants to
ensure that all processes and procedures are in place and are
being followed.
Wholesalers-distributors that distribute isotretinoin must:
To be able to distribute
Establish processes and procedures to ensure that the drug is
distributed only to certified pharmacies and authorized
wholesalers with written consent from the isotretinoin
manufacturer.
Train all relevant staff involved in distributing isotretinoin on the
program requirements.
At all times
Distribute only to certified pharmacies and authorized wholesalers
with written consent from the isotretinoin manufacturer.
Notify isotretinoin manufacturers of non-certified pharmacies or
unauthorized wholesalers-distributors that attempt to order
isotretinoin.
Return unused product to the manufacturer.
Maintain records of distribution information.
Comply with audits carried out by the Isotretinoin Applicants, or
third party acting on behalf of the Isotretinoin Applicants 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 Isotretinoin iPLEDGE REMS, see the DailyMed link on the Products tab.
This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.
What updates have been made to the REMS?
Date
Summary of change
10/03/2023
Revised to update mailing address in REMS materials.
03/24/2023
Modified to:
Make changes to the communication materials and dissemination plans to remove information that was initially used to support the October 2021 REMS modification
Make technical updates to the iPLEDGE REMS database system
Add clarifying language to the materials related to abstinence and patient risk categories.
10/06/2022
Modified to:
Make changes to the REMS document to include a requirement for pharmacies and wholesalers to comply with audits. This change is intended to align with the respective enrollment forms.
Make changes to the Non-Compliance Action Policy including updates to add a new noncompliance action for failure to comply with audit requirements for pharmacies and wholesalers.
10/08/2021
Modified to:
Remove the Medication Guide as an element of the Risk Evaluation and Mitigation Strategy (REMS)
Make changes to the REMS document and appended materials to align with labeling changes related to gender neutral patient risk categories
Make changes to the REMS appended materials to reduce redundancy and streamline the content
Make changes to the pharmacy operations to verify safe use conditions for the REMS risk management authorization
Add an optional quick reference (QR) code for use by patients enrolled in the REMS
Convert the REMS Document to the new, standardized formatModified to:
Make changes to the REMS document to include a requirement for pharmacies and wholesalers to comply with audits. This change is intended to align with the respective enrollment forms.
Make changes to the Non-Compliance Action Policy including updates to add a new noncompliance action for failure to comply with audit requirements for pharmacies and wholesalers.
12/09/2020
Modified to remove specific product information tables of currently approved isotretinoin
products from the REMS@FDA Website Screenshots
01/24/2020
Modified to make changes to the Medication Guide, an element of the
iPLEDGE REMS. This modification does not provide for any changes to the REMS document, appended
materials, or REMS supporting document.
04/23/2018
Modified to add a new sponsor, remove a product name (which is no
longer available), update a name change for a sponsor, bold text to highlight “The Do Not
Dispense After Date”, replacing radio buttons and a table with drop down menus and editorial
changes for consistency by aligning the list of birth control methods options with the listing on
the approved Birth Control Information Sheet.
06/17/2017
Modified to provide for implementation of a REMS Pharmacy Network and use of an electronic verification system for iPLEDGE Program certified pharmacies to request and receive a Risk Management Authorization (RMA) directly through the prescription claim adjudication process workflow at the point of dispensing an isotretinoin prescription. It also provides for the changes made to the REMS educational materials to streamline and improve clarity.
07/08/2016
Modified to
make minor typographical and formatting changes.
add the iPLEDGE Terms of Use text, which includes the Privacy Statement;
add the following statement in the Interactive Voice Recognition System (IVRS) public prompts for all stakeholders: “I understand and will comply with the iPLEDGE Terms of Use and Non-Compliance Action Policy. The iPLEDGE Terms of Use and the Non-Compliance Action Policy are available at www.ipledgeprogram.com”;
add a button to the www.ipledgeprogram.com website home page, “For Office Staff Designees”;
add “Find a Patient” functionality for pharmacies. This link will be accessible via the pharmacy menu, post-login; and
change the Date of Personal Significance (DOPS) Entry to prepopulate the DOPS field with forward slashes “/” and prompt users with MM/DD/YYYY.
02/04/2016
Modified to
add a Notice to Deter Patient Misclassification on select Prescriber and Designee screens to increase awareness and compliance with the appropriate classification of female patients of reproductive potential on the iPLEDGE Website
remove the Sponsor addresses from the Pregnancy Registry Protocol title page in the Appended Materials.
09/03/2015
Modified to
change the Request for Exemption for Patients with Serious Medical Reasons form as follows:
use of the Tanner Staging to classify Female Patients of Non-Childbearing Potential (FNCBP)
add an attestation requiring prescribers to evaluate patient reproductive status while receiving isotretinoin, and notify the iPLEDGE program within 10 business days of any change in the patient’s reproductive status
revise the Female Patients of Childbearing Potential (FCBP) exemption category to reflect that use of the Request for Exemption for Patients with Serious Medical Reasons is only for the first month of isotretinoin therapy
add an attestation to the monthly comprehension testing exemption category to reflect that patients are still required to successfully complete monthly pregnancy testing
standardize the terminology for female patients of childbearing potential in the REMS document, and appended REMS materials to “Females of Reproductive Potential (FRP)” and “Females of Non-Reproductive Potential (FNRP),” where applicable.
04/12/2012
Modified to
remove “Accutane” and “Roche” from the iPLEDGE materials
relocate the Non-Compliance Action Policy from the REMS document into the REMS supporting documents
relocate the following iPLEDGE website screen shots from the REMS document into the REMS supporting documents:
iPLEDGE website Prescriber web pages
iPLEDGE website Pharmacy web pages
iPLEDGEprogram.com home page
relocate the “What’s New” document from the REMS document to the REMS supporting document
remove references to specific brand names, and respective sponsor names, for
isotretinoin from the REMS educational materials
revise the “Effective Date” on the REMS educational materials to reflect the approved REMS modification approval date
make editorial changes to the Medication Guide
10/22/2010
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.
