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The goal of the Isotretinoin REMS is to mitigate the risk of embryo-fetal toxicity.
Patients’ reproductive status is assessed to determine who can get pregnant.
Patients who can get pregnant agree to use contraception or abstinence.
Before treatment initiation, patients who can get pregnant have a negative confirmatory pregnancy test.
During treatment, patients who can get pregnant have a pregnancy test prior to each dispense.
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.
Healthcare providers who prescribe isotretinoin must:
To become certified to
prescribe
Review the drug’s Prescribing Information.
Review the Prescriber Guide.
Enroll in the REMS by completing and submitting the Prescriber
Enrollment Form to the REMS.
For healthcare providers who allow patients to complete pregnancy
tests outside of a medical setting: Establish processes and
procedures to obtain pregnancy test results from the patient and to
minimize misinterpretation and falsification.
Before treatment initiation
(first dose)
Assess the patient’s reproductive status using the Prescriber Guide.
Document using the Patient Enrollment Form for Patients Who Can
Get Pregnant or Patient Enrollment Form for Patients Who Cannot
Get Pregnant.
For patients who cannot get pregnant: Counsel the patient on the
risks of isotretinoin, not to share isotretinoin, not to donate blood
while on treatment and for 30 days after stopping treatment, and
the REMS requirements using the Guide for Patients Who Cannot Get
Pregnant. Document using the Patient Enrollment Form for Patients
Who Cannot Get Pregnant.
For patients who can get pregnant: Counsel the patient on the risks
of isotretinoin and REMS requirements using the Guide for Patients
Who Can Get Pregnant. Document using the Patient Enrollment Form
for Patients Who Can Get Pregnant.
For patients who can get pregnant: Counsel the patient on the
pregnancy prevention requirements using the Guide for Patients Who Can Get Pregnant or provide the Contraception Counseling Guide
and refer the patient for expert counseling. Document using the
Patient Enrollment Form for Patients Who Can Get Pregnant.
For patients who can get pregnant: Assess the patient’s pregnancy
status by reviewing a screening pregnancy test completed in a
medical setting (e.g., prescriber’s office, clinic, laboratory) and
confirming a negative result. Document and submit the result to the
REMS using the Patient Enrollment Form for Patients Who Can Get
Pregnant.
Enroll the patient by completing and submitting the Patient
Enrollment Form for Patients Who Can Get Pregnant or Patient
Enrollment Form for Patients Who Cannot Get Pregnant to the REMS.
Provide a copy of the material to the patient.
Before treatment initiation
(first dose); at least 30 days
after the screening
pregnancy test and in the
first 5 days of the menstrual
period and immediately
before treatment
For patients who can get pregnant who have regular menstrual
cycles: Assess the patient’s pregnancy status by reviewing a
confirmatory pregnancy test completed in a medical setting (e.g.,
prescriber’s office, clinic, laboratory) and confirming a second
negative result. Document and submit the result to the REMS.
Before treatment initiation
(first dose); at least 30 days
after the screening
pregnancy test and
immediately before
treatment
For patients who can get pregnant who have amenorrhea, irregular
cycles, or use contraceptives that preclude withdrawal bleeding:
Assess the patient’s pregnancy status by reviewing a confirmatory
pregnancy test completed in a medical setting (e.g., prescriber’s
office, clinic, laboratory) and confirming a second negative result.
Document and submit the result to the REMS.
Before treatment initiation
(first dose)
For patients who can get pregnant who miss the 7-day prescription
window and have not started isotretinoin: Assess the patient’s
pregnancy status by repeating a confirmatory pregnancy test
completed in a medical setting (e.g., prescriber’s office, clinic,
laboratory) and confirming a negative result. Document and submit
the result to the REMS.
During treatment; before
each prescription
Assess the patient’s current reproductive status.
For patients who can get pregnant: Counsel the patient on the risks
of isotretinoin and REMS requirements using the Guide for Patients
Who Can Get Pregnant. Document and submit confirmation of
counseling to the REMS.
For patients who can get pregnant: Document and submit the
patient’s chosen pregnancy prevention methods (i.e., contraception
or abstinence) to the REMS.
During treatment, within 7
days before each prescription
For patients who can get pregnant: Assess the patient’s pregnancy
status by reviewing a pregnancy test and confirming a negative
result. Document and submit the result to the REMS.
During treatment
For patients who can get pregnant who miss the 7-day prescription
window: Assess the patient’s pregnancy status by repeating a
pregnancy test and confirming a negative result. Document and
submit the result to the REMS.
During treatment, on the
date of the last dose
For patients who can get pregnant: Assess the patient’s pregnancy
status by reviewing a pregnancy test and confirming a negative
result. Document and submit the result to the REMS.
After treatment
discontinuation, 30 days after
the date of the last dose
For patients who can get pregnant: Assess the patient’s pregnancy
status by reviewing a pregnancy test and confirming a negative
result. Document and submit the result to the REMS.
To maintain certification to
prescribe, annually
Review the Prescriber Guide.
Re-activate in the REMS.
At all times
Prescribe no more than a 30-day supply
Not prescribe refills
For healthcare providers who allow patients to complete pregnancy
tests outside of a medical setting: obtain pregnancy test results from
the patient and minimize misinterpretation and falsification of
pregnancy tests through the processes and procedures established
as a requirement of the REMS.
Report pregnancies to the REMS.
Patients who can get pregnant who are prescribed isotretinoin:
Before treatment initiation,
for 30 days
Adhere to the safe use condition: use your chosen pregnancy
prevention methods and not get pregnant as described in the Guide
for Patients Who Can Get Pregnant.
Before treatment initiation
Receive counseling from the prescriber on the risks of isotretinoin
and the REMS requirements.
Receive counseling from the prescriber or another expert on the
pregnancy prevention requirements.
Review the Guide for Patients Who Can Get Pregnant.
Enroll in the REMS by completing the Patient Enrollment Form for
Patients Who Can Get Pregnant with the prescriber. Enrollment
information will be provided to the REMS.
Get 2 pregnancy tests in a medical setting as directed by your
prescriber.
Complete the Comprehension Questions.
Report your chosen pregnancy prevention methods to the REMS.
For patients who miss the 7-day prescription window and have not
started isotretinoin: Get a repeat pregnancy test in a medical setting
as directed by your prescriber.
During treatment; before
each prescription
Receive counseling on the risks of isotretinoin and the REMS
requirements.
Get a pregnancy test as directed by your prescriber.
Complete the Comprehension Questions.
Report your chosen pregnancy prevention methods to the REMS.
During treatment, within 7
days of the last pregnancy
test
Get your isotretinoin from the pharmacy.
During treatment
For patients who miss the 7-day prescription window: Get a repeat
pregnancy test as directed by your prescriber.
During treatment, on the
date of the last dose
Get a pregnancy test as directed by your prescriber.
After treatment
discontinuation, 30 days after
the date of the last dose
Get a pregnancy test as directed by your prescriber.
During treatment and after
treatment discontinuation;
for 30 days
Adhere to safe use conditions: Use your chosen pregnancy
prevention methods as described in the Guide for Patients Who Can
Get Pregnant; not take isotretinoin if pregnant, breastfeeding, or not
using your chosen pregnancy prevention methods; not get pregnant;
and not donate blood.
At all times
Inform the prescriber if you get pregnant.
Adhere to safe use conditions: Not share isotretinoin.
Report the results of all pregnancy tests to your prescriber as
directed.
Patients who cannot get pregnant who are prescribed isotretinoin:
Before treatment initiation
Receive counseling from the prescriber on the risks of isotretinoin
and the REMS requirements.
Review the Guide for Patients Who Cannot Get Pregnant.
Enroll in the REMS by completing the Patient Enrollment Form for
Patients Who Cannot Get Pregnant with the prescriber. Enrollment
information will be provided to the REMS.
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
on behalf of the pharmacy.
Have the authorized representative review the Pharmacist Guide.
Have the authorized representative enroll by completing and
submitting the Pharmacy Enrollment Form to the REMS.
Train all relevant staff involved in dispensing using the Pharmacist
Guide.
Establish processes and procedures to document the authorization
number for each prescription.
For patients who can get pregnant: Establish processes and
procedures to not dispense an isotretinoin prescription after the date
provided by the REMS, reverse the authorization to dispense the
prescription, and return isotretinoin to inventory.
For patients who cannot get pregnant: Establish processes and
procedures to reverse the authorization to dispense the prescription
when isotretinoin is returned to inventory.
Before dispensing
For patients who can get pregnant: Obtain authorization to dispense
each prescription by contacting the REMS to verify the prescriber is
certified, the patient is enrolled, the patient counseling is complete,
the patient is not pregnant, the patient’s chosen pregnancy
prevention methods are confirmed, the patient’s monthly
comprehension questions are complete, and dispensing is within the
designated timeframe.
For patients who cannot get pregnant: Obtain authorization to
dispense each prescription by contacting the REMS to verify the
prescriber is certified and the patient is enrolled.
Document the authorization number for each prescription through
the processes and procedures established as a requirement of the
REMS.
To maintain certification to
dispense, annually
Have the authorized representative re-activate in the REMS.
Train all relevant staff involved in dispensing using the Pharmacist
Guide.
To maintain certification to
dispense
If the authorized representative changes, have a new authorized
representative enroll by completing and submitting the Pharmacy
Enrollment Form to the REMS.
At all times
Not dispense more than a 30-day supply.
Not dispense refills.
For patients who can get pregnant: Not dispense after the date
provided by the REMS, reverse the authorization to dispense the
prescription, and return isotretinoin to inventory through the
processes and procedures established as a requirement of the REMS.
For patients who cannot get pregnant: Reverse the authorization to
dispense the prescription when isotretinoin is returned to inventory
through the processes and procedures established as a requirement
of the REMS.
Return unused product to the manufacturer.
Not distribute, transfer, loan, or sell isotretinoin.
Maintain records of staff’s completion of training.
Maintain records that all processes and procedures are in place and
are being followed.
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 wholesalersdistributors
with written consent from the isotretinoin manufacturer.
Train all relevant staff involved in distributing isotretinoin on the
REMS requirements.
At all times
Distribute only to certified pharmacies and authorized wholesalersdistributors
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
02/09/2026
Modified to:
Remove the requirement that pregnancy tests must be performed in a CLIA certified laboratory; however, all pregnancy testing before isotretinoin treatment
initiation must be completed in a medical setting (e.g., prescriber’s office, clinic,
laboratory).
Allow prescribers the option of using home pregnancy testing for their patients
during and after isotretinoin treatment in conjunction with measures to minimize
falsification of pregnancy tests.
Remove the waiting period requirement (also referred to as the “19-day lockout”) for patients if they do not obtain isotretinoin within the first 7-day prescription
window. Before isotretinoin treatment initiation, a repeat confirmatory test must
be completed in a medical setting (as described above) without any required
waiting period.
Revise the registry requirement to remove the objective to document the
outcome (and associated data collection) for each pregnancy.
Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Before
dispensing each prescription, the authorization to dispense must verify patient
enrollment and prescriber certification.
Make changes to the REMS goals.
Make changes to the REMS educational materials to improve risk messaging, including removal of the Fact Sheet and the Office Staff Designees Activation Form, and the addition of new patient material, the Guide for Patients Who Cannot Get Pregnant.
Add the following to the list of REMS materials: The Pregnancy
Registry Healthcare Provider Guide and the Pregnancy Registry Patient Guide.
Update to the contraception counseling information, including additional
information on emergency contraception, in the REMS educational materials.
Clarify the required frequency for pharmacy staff training in the
REMS Document and Pharmacist Guide.
Make changes to the information required for the prescription authorization process and removal of the prescription window for patients who cannot get pregnant.
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 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.
