Approved Risk Evaluation and Mitigation Strategies (REMS)

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Transmucosal Immediate-Release Fentanyl (TIRF) Products
Shared System REMS
REMS last update: 09/07/2017

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Abstral (fentanyl citrate) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 022510 SENTYNL THERAPS INC 12/28/2011 setid=f969e2bc-6297-4e29-89d3-a3685a2c7c6b http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=022510
Actiq (fentanyl citrate) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 020747 CEPHALON 12/28/2011 setid=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 setid=8f549d95-985b-f783-1ebb-ef57bd2ecb05 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=021947
Lazanda (fentanyl citrate) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 022569 DEPOMED INC 12/28/2011 setid=39531d0c-db12-4627-81c9-6563076b637b http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=022569
Onsolis (fentanyl citrate) ( Info at Drugs@FDA ) NDA 022266 BDSI 12/28/2011 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=022266
Subsys (fentanyl) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 202788 INSYS DEV CO INC 01/04/2012 setid=18a413e9-11e0-4a8f-86c0-d33b37b7b771 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=202788
fentanyl buccal ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 079075 WATSON LABS 01/08/2016 setid=ad7ac196-4c6e-4aab-8742-bdb9f38f4be6 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=079075
fentanyl citrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 078907 MALLINCKRODT 01/04/2012 setid=552ba162-76ed-4bc9-8c2c-fac7a1804da0 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=078907
fentanyl citrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 077312 PAR PHARM 12/28/2011 setid=7b16f79f-33dd-4375-9f5f-b931aecf7ab8 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=077312

What is the purpose of the REMS?

The goals of the TIRF REMS Access program are to mitigate the risk of misuse, abuse, addiction, overdose and serious complications due to medication errors by:

  1. Prescribing and dispensing TIRF medicines only to appropriate patients, which includes use only in opioid-tolerant patients.
  2. Preventing inappropriate conversion between TIRF medicines.
  3. Preventing accidental exposure to children and others for whom it was not prescribed.
  4. Educating prescribers, pharmacists, and patients on the potential for misuse, abuse, addiction, and overdose of TIRF medicines.

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 Transmucosal Immediate Release Fentanyl (TIRF) medicines for outpatient use must

To become certified to prescribe
  • Review the drug’s Prescribing Information for the TIRF product.
  • Successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program, and submit to the REMS program. | Knowledge Assessment |
  • Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS program. | Prescriber Enrollment Form |
Before treatment initiation
  • Counsel the patient or their caregiver about the risks, benefits, and appropriate use of TIRF medicines using the Medication Guide.
  • Provide the patient or their caregiver with a Medication Guide for the TIRF medicine to be prescribed.
  • If converting the patient to a different TIRF medicine: counsel the patient or their caregiver about the risks, benefits, and appropriate use of TIRF medicines using the Medication Guide.
  • If converting the patient to a different TIRF medicine: provide the patient or their caregiver with a Medication Guide for the new TIRF medicine.
  • Enroll the patient by completing and submitting the TIRF REMS Access Patient-Prescriber Agreement Form to the REMS Program within ten (10) working days. Provide a completed copy of the form to the patient and retain a completed copy in the patient’s records. | Patient-Prescriber Agreement Form |
During treatment; before each prescription
  • Provide the patient or their caregiver with a Medication Guide for the TIRF medicine to be prescribed.
  • If converting the patient to a different TIRF medicine: provide the patient or their caregiver with a Medication Guide for the new TIRF medicine.
  • Assess the patient for appropriateness of the dose of the TIRF medicine, and for signs of misuse and abuse.
During treatment; every two years
  • Re-enroll the patient by completing and submitting the TIRF REMS Access Patient-Prescriber Agreement Form to the REMS Program within ten (10) working days. Provide a completed copy of the form to the patient and retain a completed copy in the patient’s records. | Patient-Prescriber Agreement Form |
To maintain certification to prescribe, every 2 years
  • Review the drug’s Prescribing Information for the TIRF product.
  • Successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program, and submit to the REMS program. | Knowledge Assessment |
  • Re-enroll in REMS by completing the Prescriber Enrollment Form and submitting it to the REMS program. | Prescriber Enrollment Form |

Patients who receive Transmucosal Immediate Release Fentanyl (TIRF) medicines

Before the first prescription
  • Enroll in the REMS Program by completing the Patient-Prescriber Agreement Form with the prescriber. Enrollment form will be provided to the REMS program. | Patient-Prescriber Agreement Form |
  • Receive counseling from the prescriber using the Medication Guide and the TIRF REMS Access Program – An Overview for Patients and Caregivers. | Patient and Caregiver Overview |
  • Receive counseling from the pharmacist on appropriate use, storage and disposal.
During treatment
  • Adhere to safe use conditions, including, following appropriate use/dosing instructions, contacting the prescriber if TIRF medicine does not relieve pain, and do not change dose and or take more often than directed.
  • Adhere to safe use conditions, including remaining opioid tolerant by continuing around-the clock opioid pain medicine for constant pain. If around-the-clock therapy has stopped, the TIRF medication must be stopped.
  • Adhere to safe use conditions, including not giving the TIRF medicine to anyone else, even if they have the same symptoms, since it may harm them or even cause death.
During treatment; every two years
  • Re-enroll in the REMS Program by completing the Patient-Prescriber Agreement Form with the prescriber. Enrollment form will be provided to the REMS program. | Patient-Prescriber Agreement Form |
At all times
  • Store the TIRF medicine in a safe place away from children and teenagers.
  • Properly dispose partially used or unneeded TIRF medicine as soon as it’s no longer needed.

Chain and independent outpatient pharmacies that dispense Transmucosal Immediate Release Fentanyl (TIRF) medicines must

To become certified to dispense
  • Be able to enable the pharmacy management system to support communication with the TIRF REMS Access program system, using established telecommunication standards and run the standardized validation test transaction to validate system enhancements.
  • Train relevant staff involved in dispensing of TIRF medicines on the risks associated with TIRF medicines and the requirements of the REMS Program using the TIRF REMS Access Education Program. | Education Program |
  • Designate an authorized representative to carry out the certification process on behalf of the pharmacy.
  • Have the authorized representative successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program and submit to the REMS Program. | Knowledge Assessment |
  • Have the authorized representative enroll in the REMS by completing the applicable enrollment forms(s): Independent Outpatient Pharmacy Enrollment Form or the Chain Outpatient Pharmacy Enrollment Form. | Pharmacy Enrollment Form (Independent Outpatient) | | Pharmacy Enrollment Form (Chain Outpatient) |
Before dispensing
  • Provide the patient or their caregiver the Medication Guide.
  • Obtain authorization to dispense each prescription by processing the prescription through the pharmacy management system.
To maintain certification to dispense; every two years
At all times
  • Maintain records of training.
  • Do not distribute, transfer, loan, or sell product.

Closed system outpatient pharmacies that dispense Transmucosal Immediate Release Fentanyl (TIRF) products must

To become certified to dispense
  • Train all relevant staff involved in dispensing TIRF medicines on the risks associated with TIRF medicines and the requirements of the REMS Program using the TIRF REMS Access Education Program.
  • Designate an authorized representative to carry out the certification process on behalf the pharmacy.
  • Have the authorized representative successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program , and submit it to the REMS Program. | Knowledge Assessment |
  • Have the authorized representative enroll in the REMS program by completing the Closed System Outpatient Pharmacy Enrollment Form. | Pharmacy Enrollment (Closed System Outpatient) |
Before dispensing
  • Counsel the patient and provide the patient with a copy of the Medication Guide.
  • Provide the patient with the Medication Guide.
  • Obtain authorization to dispense by contacting the TIRF REMS Access program for a prescription authorization number.
To maintain certification to dispense; every two years
  • Have the authorized representative successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program , and submit it to the REMS Program. | Knowledge Assessment |
  • Have the authorized representative enroll in the REMS program by completing the Closed System Outpatient Pharmacy Enrollment Form. | Pharmacy Enrollment (Closed System Outpatient) |
Ongoing
  • Maintain records of training.
  • Do not distribute, transfer, loan, or sell product.

Inpatient pharmacies that dispense Transmucosal Immediate Release Fentanyl (TIRF) products must

To become certified to dispense
  • Train all relevant staff involved in the dispensing of TIRF products on the risks of TIRF and the requirements of the REMS program using the TIRF REMS Access Education Program.
  • Establish processes and procedures to verify the appropriate patient selection and compliance with the requirements of the TIRF REMS Access program.
  • Designate an authorized representative to complete the certification process on behalf of the pharmacy(s).
  • Have the authorized representative successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program, and submit it to the REMS program. | Knowledge Assessment |
  • Have the authorized representative enroll in the REMS program by completing the Inpatient Pharmacy Enrollment Form. | Pharmacy Enrollment Form (Inpatient) |
To maintain certification to dispense; every two years
  • Have the authorized representative successfully complete the Knowledge Assessment that is included in the TIRF REMS Access Education Program, and submit it to the REMS program. | Knowledge Assessment |
  • Have the authorized representative enroll in the REMS program by completing the Inpatient Pharmacy Enrollment Form. | Pharmacy Enrollment Form (Inpatient) |
At all times
  • Do not distribute, transfer, loan, or sell TIRF medicines.
  • Do not dispense for outpatient use.

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 Transmucosal Immediate-Release Fentanyl (TIRF) Products REMS, see the DailyMed link on the Products tab.

Material Name Material Name Link
Dear Distributor Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Dear_Distributor_Letter.pdf
Dear Healthcare Provider Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Dear_Healthcare_Provider_Letter.pdf
Dear Pharmacy Letter (Inpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Dear_Inpatient_Pharmacy_Letter.pdf
Dear Pharmacy Letter (Outpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Dear_Outpatient_Pharmacy_Letter.pdf
Distributor Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Wholesaler_Distributor_Enrollment_Form.pdf
Education Program (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Education_Program_for_Prescribers_and_Pharmacists.pdf
Frequently Asked Questions (FAQs) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Frequently_Asked_Questions_FAQs.pdf
Knowledge Assessment (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Knowledge_Assessment.pdf
Patient and Caregiver Overview (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Patient_and_Caregiver_Overview.pdf
Patient-Prescriber Agreement Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Patient_Prescriber_Agreement_Form.pdf
Pharmacy Enrollment (Closed System Outpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Closed_System_Outpatient_Pharmacy_Enrollment_Form.pdf
Pharmacy Enrollment Form (Chain Outpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Chain_Outpatient_Pharmacy_Enrollment_Form.pdf
Pharmacy Enrollment Form (Independent Outpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Independent_Outpatient_Pharmacy_Enrollment_Form.pdf
Pharmacy Enrollment Form (Inpatient) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Inpatient_Pharmacy_Enrollment_Form.pdf
Prescriber Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Prescriber_Enrollment_Form.pdf
Prescriber Program Overview (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017_09-07_Prescriber_Program_Overview.pdf
Program Overview (Chain Outpatient Pharmacy) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Program_Overview_for_Chain_Outpatient_Pharmacies.pdf
Program Overview (Closed System Outpatient Pharmacy) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Program_Overview_for_Closed_System_Outpatient_Pharmacies.pdf
Program Overview (Independent Outpatient Pharmacy) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Program_Overview_for_Independent_Outpatient_Pharmacies.pdf
Program Overview (Inpatient Pharmacy) (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Program_Overview_for_Inpatient_Pharmacies.pdf
REMS document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_REMS_Document.pdf
REMS full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_Full.pdf
REMS Website Screenshot (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/TIRF_2017-09-07_REMS_Website_Screenshot.pdf

What updates have been made to the REMS?

Date Summary of change
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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