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Approved Risk Evaluation and Mitigation Strategies (REMS)

Transmucosal Immediate-Release Fentanyl (TIRF) Products
Shared System REMS
REMS last update: 12/08/2022

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Actiq (fentanyl citrate) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 020747 CEPHALON 12/28/2011 90b94524-f913-48b3-3771-7b2fcffd888a http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=020747
Fentora (fentanyl citrate) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 021947 CEPHALON 12/28/2011 8f549d95-985b-f783-1ebb-ef57bd2ecb05 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=021947
fentanyl buccal ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 079075 WATSON LABS 01/08/2016 ad7ac196-4c6e-4aab-8742-bdb9f38f4be6 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=079075
fentanyl citrate (Info at Drugs@FDA) ANDA 207338 ACTAVIS LABS FL INC 11/17/2017

What is the purpose of the REMS?

The goals of the TIRF REMS are to:
  1. Mitigate the risk of overdose by:
    1. Requiring documentation of opioid tolerance with every TIRF prescription for outpatient use.
    2. Requiring inpatient pharmacies to develop policies and procedures to verify opioid tolerance in inpatients who require TIRF medicines while hospitalized.
    3. Educating prescribers, pharmacists and patients that the safe use of TIRF medicines requires patients to be opioid-tolerant throughout treatment.
  2. Mitigate the risk of accidental exposure by educating prescribers, pharmacists and patients about proper storage and disposal of TIRF medicines.
  3. Monitor for accidental exposure, misuse, abuse, addiction, and overdose by enrolling all patients who receive a TIRF medicine for outpatient use into a registry and using surveillance systems and other data sources.

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

What assessment is available to the REMS?

Assessment Plan
REMS assessment plan unavailable for posting at this time.

What updates have been made to the REMS?

Date Summary of change
12/08/2022 Modified to change the timetable for submission of assessments in the REMS Document.
11/22/2022 Modified to revise the Actiq and Fentora Medication guides and to include a medication guide URL in order to be able to produce the medication guide electronically.
08/17/2022 Modified to make changes to the Pharmacy Education and Prescriber Education.
03/07/2022 Revised to reflect editorial changes.
12/03/2021 Modified to make changes in order to narrow the number of annual outpatient pharmacy audits required, not to exceed 400 pharmacies. The REMS Document was updated to reflect that TIRF application holders must annually audit all certified outpatient pharmacies, or a maximum of 400, that have received at least one shipment of a TIRF medicine in the past 12 months.
12/23/2020 Modified to reflect the following changes to the REMS Program:
  • Require that prescribers document a patient’s opioid tolerance with each prescription of a TIRF medicine for outpatient use;
  • Require outpatient pharmacies dispensing TIRF medicines to document and verify a patient’s opioid tolerance before dispensing;
  • Require inpatient pharmacies to develop internal policies and procedures to verify opioid tolerance in patients who require TIRF medicines while hospitalized; and
  • Require a new patient registry for use, along with other data sources, to monitor for accidental exposure, misuse, abuse, addiction, and overdose.
09/07/2017 Modified to make changes to the REMS document, and appended materials consistent with the safety label changes approved on December 16, 2016, as well as additional minor modifications.
04/11/2017 Modified to add the authorized generic and a Medication Guide that is identical to that of the branded product, except that only the authorized generic (fentanyl buccal tablets) is listed as the product name.
12/21/2015 Modified to include the new strength of 300mcg per spray in the Medication Guide.
12/24/2014 Modified to:

  1. Remove NDC Numbers from the Independent Outpatient Pharmacy Enrollment Form, Chain Outpatient Pharmacy Enrollment Form, and TIRF REMS Website.
  2. Remove reference to generic equivalents of specific products and replacement with a footnote in the Education Program for Prescribers and Pharmacists and TIRF REMS Website.
  3. Remove “Attachment 1: List of TIRF Medicines Available Only through the TIRF REMS Access Program,” and replacement with a hyperlink to the new TIRF REMS Webpage in the TIRF REMS Document, Overview for Prescribers, Prescriber Enrollment Form, Overview for Patients and Caregivers, Independent Outpatient Pharmacy Overview, Chain Outpatient Pharmacy Overview, Closed System Outpatient Pharmacy Overview, Independent Outpatient Pharmacy Enrollment Form, Chain Outpatient Pharmacy Enrollment Form, Closed System Outpatient Enrollment Form, Inpatient Pharmacy Enrollment Form, Distributor Enrollment Form, and TIRF REMS Website and Website Landing Page.
  4. Revise criteria for inactivation of Patient-Prescriber Agreement Form (PPAF) in the TIRF REMS Document.
  5. Revise to enhance knowledge about conversion of TIRF Medicines in the Education Program for Prescribers and Pharmacists and TIRF REMS Website.
  6. Add information clarifying the process to electronically transmit TIRF REMS Cash Claims in the TIRF REMS Document, TIRF REMS Access Program Frequently Asked Questions (FAQ), Independent Outpatient Pharmacy Overview, Chain Outpatient Pharmacy Overview, Closed System Outpatient Pharmacy Overview.
11/04/2014 Modified to add the Abstral product to the shared system REMS.
11/07/2013 Modified to:

  1. Revise terminology, processes, and definitions for outpatient pharmacies.
  2. Revise attestations for physicians and patients to address concerns regarding patient access.
  3. Revise Program Overview and Frequently Asked Questions to improve clarity and content.
  4. Reflect the completion of the transition phase for the TIRF REMS Access Program in the REMS materials.
06/05/2012 Modified to:

  1. Edit the Patient-Prescriber Agreement Form, add the Closed System Pharmacy Enrollment Form, add the newly approved TIRF product, Subsys (fentanyl sublingual spray), make minor editorial changes.
  2. Update the TIRF REMS Access Program “go-live” placeholder date to the actual "go-live" date of March 12, 2012.
12/28/2011 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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