Approved Risk Evaluation and Mitigation Strategies (REMS)

Buprenorphine Transmucosal Products for Opioid Dependence (BTOD)
Shared System REMS
REMS last update: 10/31/2018

What medicines are included in the REMS?

Product Name Application Number Application Holder Added to REMS DailyMed Link FDA Link
Bunavail (buprenorphine and naloxone) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 205637 BDSI 06/06/2014 12b963dd-f189-11e3-ac10-0800200c9a66 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=205637
Zubsolv (buprenorphine and naloxone) ( PI and MG at DailyMed , Info at Drugs@FDA ) NDA 204242 OREXO US INC 09/04/2013 5f5cfcfe-d52b-49e6-8fe4-550477332dd2 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=204242
buprenorphine ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 207276 RHODES PHARMS 03/27/2017 da90618a-5621-4b15-bc48-9dcc631418de http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=207276
buprenorphine ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 201760 SUN PHARM 01/29/2016 9fd1f18f-0b0f-4059-b603-19ecbf0ed63a http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=201760
buprenorphine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 201633 SUN PHARM 08/05/2016 91b68606-05de-4586-ae31-07e8cc9160cf http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=201633
buprenorphine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 207000 SPECGX LLC 12/13/2017 62abde41-46cb-4e90-a798-23d6531bf9aa
buprenorphine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 205806 DR REDDYS LABS SA 06/14/2018 72dc1ec0-7c59-a587-4ffd-c40ef79e6fb2
buprenorphine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 207607 MYLAN TECHNOLOGIES 06/14/2018 d1ecf0e8-7816-490e-b3c0-e929cb5f76de
buprenorphine and naloxone (Info at Drugs@FDA) NDA 208042 TEVA PHARMS USA 09/07/2018
buprenorphine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 205022 LANNETT CO INC 09/19/2016 14eaa94a-cc8a-4e1e-8cfb-5c976c96c606 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=205022
buprenorphine hydrochloride ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 090622 ETHYPHARM 02/22/2013 a891f3ff-5cad-4e92-b4c4-d5108c8df550 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=090622
buprenorphine hydrochloride ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 090819 ACTAVIS ELIZABETH 02/19/2015 03819118-86f6-4329-adaf-4599e7b71f46 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=090819
buprenorphine hydrochloride ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 201066 MYLAN 03/06/2015 7a85f424-9d83-49d9-8a17-478abce6fddd http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=201066
buprenorphine hydrochloride ( Info at Drugs@FDA ) ANDA 090279 CASI PHARMS INC 06/10/2015 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=090279
buprenorphine hydrochloride ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 078633 HIKMA 02/22/2013 1bf8b35a-b769-465c-a2f8-099868dfcd2f http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=078633
buprenorphine hydrochloride ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 090360 BARR 02/22/2013 593aa0cf-bbcd-14b5-e053-2a91aa0a13e5 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=090360
buprenorphine hydrochloride and naloxone hydrochloride ( PI at DailyMed , Info at Drugs@FDA , Info at Drugs@FDA ) ANDA 205954 ALVOGEN PINE BROOK 4210afeb-474c-d842-d68e-af7e0021851a
buprenorphine hydrochloride and naloxone hydrochloride dihydrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 203136 AMNEAL PHARMS 02/22/2013 17b63f10-c9df-44be-80fa-6f1c305583b8 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203136
buprenorphine hydrochloride and naloxone hydrochloride dihydrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 204431 ETHYPHARM USA CORP 10/16/2015 47236a95-ba0b-4f6a-b406-858cabc726df http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=204431
buprenorphine hydrochloride and naloxone hydrochloride dihydrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 091149 TEVA PHARMS USA 09/09/2014 b39c724f-7dc1-4213-8671-83c34a82268a http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=091149
buprenorphine hydrochloride and naloxone hydrochloride dihydrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 203326 HIKMA 06/27/2014 713db2c6-0544-4633-b874-cfbeaf93db89 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203326
buprenorphine hydrochloride and naloxone hydrochloride dihydrate ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 091422 ACTAVIS ELIZABETH 02/22/2013 6cccf229-9611-4b6f-8f1b-acc8ff1ed3f8 http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=091422
buprenorpine and naloxone ( PI and MG at DailyMed , Info at Drugs@FDA ) ANDA 205299 DR REDDYS LABS SA 06/14/2018 718756d7-0131-b173-6c45-5ee039b311b0

What is the purpose of the REMS?

The goals of the Buprenorphine-containing Transmucosal products for Opioid Dependence (BTOD) REMS are to:

  1. Mitigate the risks of accidental overdose, misuse, and abuse.
  2. Inform prescribers, pharmacists, and patients of the serious risks associated with buprenorphine-containing products.

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

Health Care Providers who prescribe or dispense buprenorphine transmucosal products for opioid dependence (BTOD) must

Before treatment initiation (first dose)
  • Assess the patient’s condition to verify the patient meets the diagnostic criteria for opioid dependence.
  • Counsel the patient on the risks described in the professional information and Medication Guide and safe storage of the medication.
  • Complete the Appropriate Use Checklist. Retain a completed copy in the patient’s record or by using another method (e.g. electronic health record) specific to the prescriber’s office practice.
During treatment; at the first visit following induction
  • Prescribe a limited amount of medication.
During treatment; at a return visit scheduled at intervals commensurate with patient stability
  • Assess the patient’s compliance with the prescribed medication, appropriateness of the dosage prescribed, whether patient is receiving the necessary psychosocial support, and whether patient is making adequate progress towards treatment goals
  • Complete the Appropriate Use Checklist. Retain a completed copy in the patient’s record or by using another method (e.g. electronic health record) specific to the prescriber’s office practice.

Patients who are prescribed buprenorphine transmucosal for opioid dependence (BTOD) products

Before the first prescription
  • Receive counseling from the prescriber on the risks and safe storage of the medication.
During treatment; at a time interval determined by your prescriber
  • Be monitored for compliance with the prescribed medication, appropriateness of the dosage prescribed, assessment of whether receiving the necessary psychosocial support, and whether making adequate progress towards treatment goals

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 Buprenorphine Transmucosal Products for Opioid Dependence (BTOD) REMS, see the DailyMed link on the Products tab.

Material Name Material Name Link
Appropriate Use Checklist (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_Appropriate_Use_Checklist.pdf
Dear Pharmacist Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_Dear_Pharmacist_Letter.pdf
Dear Prescriber Letter (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_Dear_Prescriber_Letter.pdf
Pharmacist Brochure (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_Pharmacist_Brochure.pdf
Prescriber Brochure (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_Prescriber_Brochure.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_REMS_Full.pdf
REMS Website Screenshots (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2018_10_31_REMS_Website_Screenshots.pdf

What updates have been made to the REMS?

Date Summary of change
10/31/2018 Modified to align the REMS document and materials with the approved labeling. Those labeling changes pertained to the risks of life-threatening respiratory depression and death with concomitant use of buprenorphine with benzodiazepines or other CNS depressants, and additional revisions to the Package Insert.
09/07/2018 Modified to add Cassipa (buprenorphine and naloxone) product information.
05/23/2017 Modified to align the REMS document and materials to the labeling approved on December 16, 2016, as well as additional minor modifications.
01/23/2017 Revised to correct a typographical error(s).
10/04/2016 Modified to include the proposed new strength into the Dose Comparison Chart included in both the Prescriber Brochure, "Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Prescribers" and the Pharmacist Brochure, "Office Based Buprenorphine Therapy for Opioid Dependence: Important Information for Pharmacists."
07/27/2016 Revised to correct a typographical error(s).
07/07/2016 Modified to provide more succinct and clearer risk information for prescribers and pharmacists in the Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Pharmacists Brochure, Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Prescribers Brochure the Appropriate Use Checklist, Dear Prescriber Letter, and Dear Pharmacist Letter.
08/10/2015 Modified to update language to permit the use of Zubsolv for the initial (“induction”) treatment of opioid dependence in the Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Pharmacists brochure and the Office-Based Buprenorphine Therapy for Opioid Dependence: Important Information for Prescribers brochure.
06/04/2015 Modified to add a new strength of Zubsolv: 2.9 mg buprenorphine/ 0.71 mg naloxone to the REMS appended materials.
02/12/2015 Modified to:

  1. Add two new strengths of Zubsolv: 8.6 mg buprenorphine/ 2.1 mg naloxone and 11.4 mg buprenorphine/ 2.9 mg naloxone.
  2. Add Bunavail (buprenorphine/naloxone) buccal film product information.
  3. Change the indication for Suboxone (buprenorphine and naloxone) sublingual film to include the use of Suboxone (buprenorphine and naloxone) sublingual film in all phases of treatment for opioid dependence.
    1. Limitations of use in initial treatment to patients physically dependent on heroin or other short-acting opioids.
  4. Add a new warning regarding use in patients with hepatic impairment.
  5. Update language on use in pregnancy, nursing mothers, and patients with hepatic impairment.
06/06/2014 Modified to add Bunavail (buprenorphine and naloxone) product information to the shared system REMS.
09/04/2013 Modified to:

  1. Revise one of the goals to include informing prescribers and pharmacists of the serious risks associated with buprenorphine-containing products.
  2. Add a timetable for submission of assessments for the NDA holder(s) of the BTOD REMS.
  3. Update REMS materials to reflect the addition of a new product to the BTOD REMS including information on how the new product differs from the currently available products, how to switch between products, and recommended dosing.
02/22/2013 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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