CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`022410Orig1s000
`
`
`REMS
`
`
`
`
`
`
`

`

`Initial REMS Approval: August 30, 2010
`
`
`
`
`
`
`NDA 22-410
`
`SUBOXONE® (buprenorphine and naloxone) sublingual film CIII
`
`Buprenorphine (opioid partial agonist-antagonist)
`
`Naloxone (opioid antagonist)
`
`Reckitt Benckiser Pharmaceuticals Inc.
`
`
`10710 Midlothian Turnpike, Suite 430
`
`
`Richmond, VA 23235
`
`
`Telephone: 804-379-1090
`
`
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`This REMS does not apply to SUBOXONE film dispensed to patients admitted to an
`
`Opioid Treatment Program under 42 CFR Part 8.
`
`
`I.
`GOAL(S):
`
`The goals of the SUBOXONE film risk evaluation and mitigation strategy are to:
`
`
`
`
`
`
`
`Mitigate the risks of accidental overdose, misuse and abuse
`
`Inform patients of the serious risks associated with SUBOXONE film
`
`REMS ELEMENTS:
`
`
`II.
`
`A. Medication Guide
`A Medication Guide will be dispensed with each SUBOXONE film prescription
`in accordance with 21 CFR 208.24.
`
`
`B.
`
`
`
`
`Elements to Assure Safe Use
`
`
`1. Safe use conditions
`
`
`a. SUBOXONE film will only be dispensed by the prescriber or
`prescribed to patients with documentation of the following safe use
`conditions:
`i. Verification that the patient meets the diagnostic criteria for opioid
`dependence.
`
`1
`
`

`

`Initial REMS Approval: August 30, 2010
`
`
`
`
`
`ii. Risks described in the professional labeling and the Medication
`Guide have been discussed with the patient.
`
` iii. Safe storage of the medication has been explained and reviewed
`with the patient.
`iv. After appropriate induction, the patient is prescribed a limited
`amount of medication at the first visit.
`b. Prescribers will document safe use conditions for each patient by using
`the ‘Appropriate Use Checklist,’ or by using another method (e.g.
`electronic health record) specific to the prescriber’s office practice.
`c. Reckitt Benckiser Pharmaceuticals Inc. will ensure that within 30 days
`
`of FDA approval of the SUBOXONE REMS, a REMS Instruction
`Letter to Prescribers will be mailed to all physicians certified to treat
`opioid dependence under the Drug Addiction Treatment Act of 2000
`(DATA 2000). This letter is designed to convey and reinforce the risks
`of accidental overdose, misuse, and abuse of SUBOXONE, as well as
`the need to appropriately monitor patients and document safe use
`conditions.
`d. Reckitt Benckiser Pharmaceuticals Inc. will, on a monthly basis,
`identify any newly DATA 2000-certified physicians and mail the
`applicable documents to them. The following materials will be
`appended to the Prescriber Instruction Letter: Medication Guide, Full
`
`Prescribing Information, Physician Brochure, and the Appropriate Use
`
`Checklist.
`e. To further reinforce safe use conditions, Reckitt Benckiser
`Pharmaceuticals Inc. will ensure that within 30 days of FDA approval
`of the SUBOXONE REMS, a REMS Introductory Letter for
`Pharmacists will be mailed to all pharmacists on a national mailing list
`from the American Pharmacists Association. The following materials
`will be appended to the Introductory Pharmacist Letter: Medication
`
`Guide, Full Prescribing Information and the Pharmacist Brochure.
`
`
`
`2
`
`

`

`Initial REMS Approval: August 30, 2010
`
`
`
`
`
`f. Reckitt Benckiser Pharmaceuticals Inc. will make the letters and all
`materials that are appended to the letters available through its toll-free
`information line, through its field personnel, and on the product
`website.
`
`
` 2. Monitoring
`
`a. Each patient using SUBOXONE film will be subject to the following
`monitoring:
`
`
`i. Return visits are scheduled at intervals commensurate with patient
`stability. Weekly, or more frequent, visits are recommended for
`the first month.
`
`ii. Assessment and reinforcement of patient’s compliance with the
`prescribed medication.
`
`iii. Assessment of appropriateness of dosage prescribed.
`
`iv. Assessment of whether patient is receiving the necessary
`psychosocial support.
`
`v. Assessment of whether patient is making adequate progress
`towards treatment goals.
`b. Prescribers will document that each patient has received the required
`clinical monitoring using the ‘Appropriate Use Checklist,’ or by using
`another method/system (e.g. electronic health record) specific to the
`prescriber’s office practice.
`The following materials are part of the REMS and are appended to the REMS
`document:
`
` SUBOXONE film Medication Guide
`
`
` REMS Instruction Letter to Prescribers
`
`
` REMS Introductory Letter to Pharmacists
`
`
` Appropriate Use Checklist
`
`
` Physician Brochure, “Important Information for Physicians-
`Frequently Asked Questions”
`
`
`
`
`3
`
`

`

`
`
` Initial REMS Approval: August 30, 2010
`
`
`
` Pharmacist Brochure, “Important Information for Pharmacists-
`Frequently Asked Questions”
`
`
`Implementation System
`The Implementation System includes the following:
`
`1. Reckitt Benckiser Pharmaceuticals Inc. will ensure that all DATA 2000-
`certified physicians receive the Instruction Letter with the appended materials.
`
`2. Reckitt Benckiser Pharmaceuticals Inc. will monitor compliance with the
`requirements to document prescribing and dispensing with documentation of
`safe use conditions through surveys of patients and prescribers, evaluations of
`health care utilization databases, and ongoing surveillance (sources including,
`but not limited to, internet, street ethnography, national databases, and surveys
`conducted at substance abuse treatment programs).
`
`3. Reckitt Benckiser Pharmaceuticals Inc. will monitor and evaluate the
`implementation of the elements to assure safe use provided for under Sections
`B1, above, and in the manner described in the REMS supporting document,
`and will take reasonable steps to improve implementation of these elements to
`meet the goals of the REMS.
`
`Timetable for Submission of Assessments
`Reckitt Benckiser Pharmaceuticals Inc. will submit REMS Assessments to FDA
`at 6 months and at 12 months for the first year from the date of approval of the
`REMS, then annually thereafter. To facilitate inclusion of as much information
`as possible, while allowing reasonable time to prepare the submission, the
`reporting interval covered by each assessment will conclude no earlier than 60
`days before the submission date for that assessment. Reckitt Benckiser
`Pharmaceuticals Inc. will submit each assessment so it will be received by the
`FDA on or before the due date.
`
`4
`
`
`C.
`
`
`
`D.
`
`
`
`

`

`
`
`SUBOXONE® (buprenorphine and naloxone) (CIII)
`
`SUBUTEX® (buprenorphine) (CIII)
`
`
`IMPORTANT SAFETY INFORMATION FOR PRESCRIBERS
`
`
`<DATE>
`
`
`Dr. <FIRST NAME> <LAST NAME>
`
`<ADDRESS 1>
`
`<ADDRESS 2>
`
`<CITY>, <STATE> <ZIP>
`
`
`Dear Dr. <LAST NAME>:
`
`
`Since you are a prescriber certified to treat opioid dependence under the Drug Addiction
`
`Treatment Act of 2000 (DATA 2000), Reckitt Benckiser Pharmaceuticals Inc. is
`
`informing you about its new Risk Evaluation and Mitigation Strategy (REMS) for
`
`SUBOXONE and SUBUTEX. Under the Drug Addiction Treatment Act (DATA)
`
`codified at 21 U.S.C. 823(g), prescription use of these products in the treatment of opioid
`
`dependence is limited to physicians who meet certain qualifying requirements, and who
`
`have notified the Secretary of Health and Human Services (HHS) of their intent to
`
`prescribe this product for the treatment of opioid dependence and have been assigned a
`
`unique identification number that must be included on every prescription.
`
`
`The REMS is a requirement from the Food and Drug Administration (FDA) to ensure the
`
`benefits of SUBOXONE and SUBUTEX outweigh the risks of accidental overdose,
`
`
`misuse and abuse. SUBOXONE and SUBUTEX sublingual tablets are indicated for the
`
`treatment of opioid dependence. SUBOXONE sublingual film is indicated for the
`
`maintenance treatment of opioid dependence. These products should be used as part of a
`
`complete treatment plan to include counseling and psychosocial support.
`
`
`
`This REMS does not apply to SUBOXONE or SUBUTEX dispensed to patients admitted
`
`to Opioid Treatment Programs (OTP) under 42 CFR Part 8 because the care of these
`
`patients is subject to specific requirements under those regulations.
`
`
`Certified prescribers, treating patients outside of OTPs, must meet the requirements of
`
`the SUBOXONE and SUBUTEX REMS and ensure safe use conditions. Reckitt
`
`Benckiser Pharmaceuticals asks that you take the following ten actions and document
`
`the completion of these actions:
`
`
`
` Verify patient meets diagnostic criteria for opioid dependence
`
`
` Review Medication Guide with patient
`
`
` Provide induction doses under appropriate supervision
`
`
` Prescribe a limited amount of medication during the initial stages of treatment
`
`
`
`
`1
`
`
`

`

`
` Schedule patient appointments commensurate with patient stability (weekly or more
`frequent visits recommended for the first month)
`
` Consider pill count/dose reconciliation
`
` Assess whether the patient is receiving the counseling/psychosocial support
`considered necessary for treatment
`
` Assess whether the patient is making progress toward treatment goals, including, as
`appropriate, urine toxicology testing
`
` Continually assess appropriateness of maintenance dose
`
` Continually assess benefits of treatment outweigh the risks
`
`An Appropriate Use Checklist is enclosed to assist you in complying with this
`requirement of the REMS. You may use other means (e.g. electronic health record)
`specific to your office practice to document that the above actions have been
`completed for your patient.
`
`In addition, the REMS includes a Medication Guide with important information to be
`reviewed with patients. Six key messages that need to be communicated to patients
`about the risks of accidental overdose, misuse and abuse include:
`
`
`
` Warn patients that it is extremely dangerous to self-administer non-prescribed
`benzodiazepines or other central nervous system (CNS) depressants (including
`alcohol) while taking SUBOXONE or SUBUTEX. Patients prescribed
`benzodiazepines or other CNS depressants should be cautioned to use them only as
`directed by their physician.
`
`
`
` Advise patients that SUBOXONE and SUBUTEX contain an opioid that can be a
`target for people who abuse prescription medications or street drugs. Patients should
`be cautioned to keep their tablets in a safe place, and to protect them from theft.
`
`
`
`
`
`Instruct patients to keep SUBOXONE and SUBUTEX in a secure place, out of the
`sight and reach of children. Accidental or deliberate ingestion by a child may cause
`respiratory depression that can result in death. Patients should be advised that if a
`child is exposed to SUBOXONE or SUBUTEX, medical attention should be sought
`immediately.
`
`
`
` Advise patients never to give SUBOXONE or SUBUTEX to anyone else, even if he
`or she has the same signs and symptoms. It may cause harm or death.
`
`
`
` Advise patients that selling or giving away this medication is against the law.
`
`Additional important safety information can be in found in the enclosed Prescriber
`Brochure and the full Prescribing Information.
`You are also encouraged to report adverse events from prescription drugs to the FDA.
`Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
`
`
`
`2
`
`
`

`

`If you have an adverse event to report or any questions, please call our Medical
`
`Information Unit at 1-877-SUBOXONE (782-6966) or go online to www.suboxone.com.
`
`
`
`Sincerely,
`
`
`
`
`<NAME>
`
`<TITLE>
`
`Reckitt Benckiser Pharmaceuticals Inc
`
`
`Enclosures:
`Appropriate Use Checklist
`Important Information for Physicians Brochure
`Medication Guide
`Full Prescribing Information
`
`Rev. 08/2010
`
`
`
`
`3
`
`

`

`SUBOXONE® (buprenorphine and naloxone) (CIII)
`
`SUBUTEX® (buprenorphine) (CIII)
`
`
`IMPORTANT SAFETY INFORMATION FOR PHARMACISTS
`
`
`<DATE>
`
`
`<FIRST NAME> <LAST NAME>
`
`<ADDRESS 1>
`
`<ADDRESS 2>
`
`<CITY>, <STATE> <ZIP>
`
`
`Dear <LAST NAME>:
`
`
`Reckitt Benckiser Pharmaceuticals Inc (RBP) is informing you about its new Risk
`
`Evaluation and Mitigation Strategy (REMS) for SUBOXONE and SUBUTEX. Under the
`
`Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of
`
`these products in the treatment of opioid dependence is limited to physicians who meet
`
`certain qualifying requirements, and who have notified the Secretary of Health and
`
`Human Services (HHS) of their intent to prescribe this product for the treatment of opioid
`
`dependence and have been assigned a unique identification number that must be included
`
`on every prescription.
`
`
`The REMS is a requirement from the Food and Drug Administration (FDA) to ensure the
`
`benefits of SUBOXONE and SUBUTEX outweigh the risks of accidental overdose,
`
`misuse and abuse. SUBOXONE and SUBUTEX sublingual tablets are indicated for the
`
`treatment of opioid dependence. SUBOXONE sublingual film is indicated for the
`
`maintenance treatment of opioid dependence. These medications should be used as part
`
`of a complete treatment plan to include counseling and psychosocial support.
`
`
`
`This REMS does not apply to SUBOXONE or SUBUTEX dispensed to patients admitted
`
`to Opioid Treatment Programs (OTP) under 42 CFR Part 8 because the care of these
`
`patients is subject to specific requirements under those regulations.
`
`
`The goals of the SUBOXONE and SUBUTEX REMS are to:
`
`
`• Mitigate the risks of accidental overdose, misuse and abuse
`
`Inform patients of the serious risks associated with SUBOXONE and
`
`•
`
`SUBUTEX.
`
`
`
`To comply with RBP REMS commitments, we ask that you provide a Medication
`Guide to your patients or their caregivers with each dispensing and encourage them to
`read it. The Medication Guide provides important information on the safe and
`effective use of SUBOXONE and SUBUTEX, and the importance of participating in
`psychosocial support. Six key messages that should be communicated are:
`
`
`
`
`1
`
`
`

`

`
`• Warn patients that it is extremely dangerous to self-administer non-prescribed
`benzodiazepines or other central nervous system (CNS) depressants (including
`alcohol) while taking SUBOXONE or SUBUTEX. Patients prescribed
`benzodiazepines or other CNS depressants should be cautioned to use them only as
`directed by their physician
`
`
`
`• Advise patients that SUBOXONE and SUBUTEX contain an opioid that can be a
`target for people who abuse prescription medications or street drugs. Patients should
`be cautioned to keep their tablets in a safe place, and to protect them from theft
`
`
`
`•
`
`Instruct patients to keep SUBOXONE and SUBUTEX in a secure place, out of the
`sight and reach of children. Accidental or deliberate ingestion by a child may cause
`respiratory depression that can result in death. Patients should be advised that if a
`child is exposed to SUBOXONE or SUBUTEX, medical attention should be sought
`immediately
`
`
`
`• Advise patients never to give SUBOXONE or SUBUTEX to anyone else, even if he
`or she has the same signs and symptoms. It may cause harm or death
`
`
`
`• Advise patients that selling or giving away this medication is against the law
`
`Medication Guides will be provided for SUBOXONE film within the primary packaging
`of the drug, only for the film formulation. Tear pads of Medication Guides will be
`provided to pharmacies by RBP for SUBOXONE film and SUBOXONE and SUBUTEX
`tablets. If you require additional Medication Guides you may:
`
`
`• Contact RBP’s Medical Information Unit at 1-877-SUBOXONE (1-877-782­
`6966)
`
`
`• Print copies from the SUBOXONE website (www.suboxone.com)
`
`Additional important safety information can be found in the enclosed Pharmacist
`Brochure and the full Prescribing Information.
`
`You are also encouraged to report adverse events from prescription drugs to the FDA.
`Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
`
`If you have an adverse event to report or any questions, please call our Medical
`Information Unit at 1-877-SUBOXONE (1-877-782-6966) or go online to
`www.suboxone.com.
`
`Sincerely,
`
`
`
`<NAME>
`<TITLE>
`
`
`
`2
`
`
`

`

`Reckitt Benckiser Pharmaceuticals Inc
`
` Medication Guide
`Important Information for Pharmacists Brochure
`Full Prescribing Information
`
`Enclosures:
`
`
`
`
`Rev. 08/2010
`
`
`
`
`
`3
`
`
`

`

`
`
`
`
`
`
`SUBOXONE® and SUBUTEX® APPROPRIATE USE CHECKLIST
`
`
`
`Patient Name: __________________________________________________________________________________
`
`
`As a healthcare provider who prescribes SUBOXONE® (buprenorphine and naloxone) sublingual film CIII, SUBOXONE®
`
`(buprenorphine and naloxone) sublingual tablets CIII, or SUBUTEX® (buprenorphine) sublingual tablets CIII, you may find
`this checklist a useful reminder of the safe use conditions and monitoring requirements to be addressed during each
`
`patient’s appointment. These include: 1) understanding and reinforcement of safe use conditions, 2) the importance of
`
`psychosocial counseling, and 3) screening and monitoring patients to determine progress towards treatment goals.
`
`If a patient continues to abuse various drugs or is unresponsive to treatment, including psychosocial intervention, it is
`
`important that you assess the need to refer the patient to a specialist and/or more intensive behavioral treatment
`
`environment.
`
`
`
`Additional resource: Physician Clinical Support System: http://www.pcssbuprenorphine.org/
`
`
` Measurement to Ensure
`
` Appropriate Use
`
`Visit 4
`
`Visit 5
`
`Visit 6
`
`Visit 7
`
`Intake/
`Induction
`
`Visit 1
`
`Visit 2
`
`Visit 3
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Date:
`Induction
`
`Verified patient meets
`diagnostic criteria for
`opioid dependence
`
`Discussed risks described
`in professional labeling
`and Medication Guide with
`patient
`
`
`Explained or reviewed
`conditions of safe storage
`of medication
`
`Provided induction doses
`under appropriate
`
`supervision
`
`Prescribed limited amount
`of medication at first visit
`Scheduled next visit at
`interval commensurate
`with patient stability
`
`
` weekly, or more
`frequent visits
`recommended for the
`first month
`Maintenance
`
`Assessed and encouraged
`patient to take medication
`as prescribed
`
` Consider pill
`count/dose
`
`reconciliation
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`SUBOXONE® and SUBUTEX® APPROPRIATE USE CHECKLIST
`
`Intake/
`Induction
`
`Visit 1
`
`Visit 2
`
`Visit 3
`
`Visit 4
`
`Visit 5
`
`Visit 6
`
`Visit 7
`
`
`
`
` Measurement to Ensure
`
` Appropriate Use
`
`
`
`
`
`
`
`
`
`
`
`
`
`Date:
`Maintenance (continued)
`
`Assessed appropriateness of
`dosage
`
` Suboxone 12 mg –16 mg
`is recommended for
`maintenance
`
` Doses higher than this
`should be an exception
`
` The need for higher dose
`
`should be carefully
`
`evaluated
`
`Assessed whether patient is
`receiving the psychosocial
`support considered
`necessary
`
`
`Assessed whether benefits
`of treatment with Suboxone
`outweigh risks associated
`with Suboxone
`
`Assessed whether patient is
`making adequate progress
`toward treatment goals
` Conduct urine drug
`screens as appropriate to
`assess use of illicit
`substances
` Consider referral to more
`
`intensive forms of
`treatment for patients not
`making progress
`
`Scheduled next visit at
`
`interval commensurate with
`
`patient stability
`
` weekly, or more frequent
`visits are recommended
`for the first month
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
`
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`
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`
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`
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`
`
`SUBOXONE (buprenorphine and naloxone) sublingual tablets and sublingual film CIII
`
`SUBUTEX (buprenorphine) sublingual tablets CIII
`SUBOXONE® and SUBUTEX® are registered trademarks of Reckitt Benckiser Healthcare (UK) Ltd.
`
`
`
`2
`
`

`

`Initiating Office-Based Opioid Therapy
`
`
`
`
`Important
`
`Information
`
`for Physicians
`
`
`Frequently Asked Questions
`
`
`
`
`
`
`
`SUBOXONE®
`
`
`(buprenorphine and naloxone) sublingual film CIII
`
`
`
`
`1
`
`
`

`

`Introduction
`I.
`The purpose of this brochure is to provide information about the Risk Evaluation and
`Mitigation Strategy (REMS) to prescribers of SUBOXONE® (buprenorphine and
`naloxone) sublingual film CIII who are certified to treat opioid dependence under the
`Drug Addiction Treatment Act of 2000 (DATA 2000; See Appendix A)
`
`This brochure summarizes important safety issues and messages needed to counsel
`patients about safe use of SUBOXONE.
`
`This REMS does not apply to SUBOXONE film dispensed to patients admitted to Opioid
`Treatment Programs under 42 CFR Part 8 because the care of these patients is subject to
`specific requirements under those regulations.
`
`What is SUBOXONE?
`SUBOXONE sublingual film is indicated for the maintenance treatment of opioid
`dependence and should be used as part of a complete treatment plan to include counseling
`and psychosocial support.
`
`SUBOXONE contains the active ingredient buprenorphine HCl. The sublingual film
`
`formulation is administered sublingually as a single daily dose. SUBOXONE is intended
`to be part of a treatment plan that includes counseling and/or behavioral therapy.
`
`SUBOXONE includes a second active ingredient, naloxone HCl, at a ratio of 4:1
`buprenorphine/naloxone (ratio of free bases). Naloxone is included in the SUBOXONE
`formulation, and is intended to deter individuals from abusing it by the intravenous route.
`
`How is SUBOXONE sublingual film different from the tablet formulation?
`The primary difference is the delivery mechanism of the sublingual formulation.
`SUBOXONE sublingual film contains buprenorphine and naloxone, similar to the tablet
`formulation. The dosage strengths for SUBOXONE are the same as the tablet
`formulation: 2/0.5 mg and 8/2 mg.
`II. REMS – Risk Evaluation and Mitigation Strategy
`What is a Risk Evaluation and Mitigation Strategy (REMS)?
`A REMS is a strategy to manage a known or potential risk associated with a drug. A
`REMS can include, among other strategies, a Medication Guide, a communication plan,
`and elements to assure safe use.
`
`Is there a REMS for SUBOXONE?
`Yes, a REMS has been implemented as part of the FDA requirements to ensure that the
`benefits of treatment with SUBOXONE outweigh the potential risks, particularly risks of
`accidental overdose, misuse, and abuse.
`
`What are the goals of the SUBOXONE REMS?
`
`
`
`2
`
`
`

`

`The goals of the REMS for SUBOXONE are to:
`
`
`1. Mitigate the risks of accidental overdose, misuse, and abuse
`
`2. Inform physicians, pharmacists and patients of the serious risks associated with the
`use of SUBOXONE
`
`What is my role with regard to the REMS for SUBOXONE?
`To meet the requirements of the REMS and to ensure the benefits of prescribing
`SUBOXONE to a patient outweigh the risks of accidental overdose, misuse and abuse,
`physicians should take the following measures and document actions taken with each
`
`patient to ensure safe use conditions.
`
`• Verify patient meets diagnostic criteria for opioid dependence
`
`• Discuss the risks associated with SUBOXONE, including those described in the
`Medication Guide
`
`• Provide induction doses under appropriate supervision
`
`• Prescribe a limited amount of medication during the initial stages of treatment
`
`• Explain how to safely store the medication
`
`• Schedule patient appointments commensurate with patient stability (weekly or
`more frequent visits recommended for the first month)
`
`• Consider pill count/dose reconciliation
`
`• Assess whether patient is receiving counseling/psychosocial support considered
`necessary for treatment
`
`• Assess whether patient is making progress toward treatment goals (including, as
`appropriate, urine toxicology testing)
`
`• Continually assess appropriateness of maintenance dose
`
`• Continually assess whether or not benefits of treatment outweigh the risks.
`
`
`As part of the REMS, physicians prescribing SUBOXONE for opioid dependence will be
`provided with an ‘Appropriate Use Checklist’ to document safe use conditions and
`clinical monitoring of each patient. This can be retained in the records of each patient.
`
`
`
`This REMS does not apply to SUBOXONE film dispensed to patients admitted to Opioid
`Treatment Programs under 42 CFR Part 8 because the care of these patients is subject to
`specific requirements under those regulations.
` III. Highlighted Important Safety Information for
`SUBOXONE
`This section of the brochure highlights important safety information to consider when
`prescribing SUBOXONE. Refer to the prescribing information (PI) for detailed
`
` safety-related information for SUBOXONE.
`
`Abuse Potential for SUBOXONE
`
`Is SUBOXONE abusable?
`
`
`
`3
`
`
`

`

`Buprenorphine like morphine and other opioids, has the potential for being abused and is
`subject to criminal diversion. This should be considered when prescribing or dispensing
`buprenorphine in situations when the clinician is concerned about an increased risk of
`misuse, abuse, or diversion. Healthcare professionals should contact their state
`professional licensing board or state controlled substances authority for information on
`how to prevent and detect abuse, misuse, or diversion of this product.
`
`Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids
`should be provided with, or referred to, more intensive and structured treatment.
`
`Abuse of buprenorphine poses a risk of overdose and death. This risk is increased with
`
`the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines.
`
`The physician may be able to more easily detect misuse or diversion by maintaining
`records of medication prescribed including date, dose, quantity, frequency of refills, and
`renewal request of medication prescribed.
`
`Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of
`therapy, and proper handling and storage of the medication are appropriate measures that
`help to limit abuse of opioid drugs.
`
`Because it contains naloxone, SUBOXONE is highly likely to produce marked and
`intense withdrawal signs and symptoms if misused parenterally by individuals dependent
`on full opioid agonists such as heroin, morphine, or methadone. SUBUTEX does not
`contain a naloxone component. Therefore, to discourage misuse or abuse, it is highly
`recommended that SUBOXONE is prescribed whenever feasible.
`
`Clinicians should also be aware that some opioid-dependent persons, particularly those
`with a low level of full mu-opioid physical dependence or those whose opioid physical
`dependence is predominantly to buprenorphine, abuse buprenorphine/naloxone
`combinations by the intravenous or intranasal route.
`
`Because of the partial agonist properties of buprenorphine, SUBOXONE may precipitate
`opioid withdrawal signs and symptoms in such persons if administered sublingually
`before the agonist effects of the opioid have subsided.
`
`Can SUBOXONE cause dependence?
`Buprenorphine, the active ingredient in SUBOXONE is a partial agonist at the mu-opioid
`receptor. Chronic administration produces dependence of the opioid type, characterized
`by withdrawal upon abrupt discontinuation or rapid taper. The withdrawal syndrome is
`milder than seen with full agonists, and may be delayed in onset. Buprenorphine can be
`abused in a manner similar to other opioids, legal or illicit. This should be considered
`when prescribing or dispensing buprenorphine in situations where there is concern about
`
`an increased of misuse, diversion, or abuse.
`
`What precautions should I take in my practice to prevent diversion and abuse?
`You should consider the following suggestions:
`
`
`
`4
`
`
`

`

`
`•
`
`Initiate treatment with supervised administration, progressing to unsupervised
`administration as your patient’s clinical stability permits
`
`• Limit the use of buprenorphine-only products, such as buprenorphine sublingual
`
` tablets to supervised use, wherever possible. Point out to the patient that
`SUBOXONE products contain naloxone. The naloxone in SUBOXONE is likely to
`precipitate withdrawal signs and symptoms when injected by individuals dependent
`on heroin, morphine, or other full opiate agonists. It is strongly recommended that
`SUBOXONE be used whenever unsupervised administration is planned
`
`• As your patients progress beyond induction to a stabilized dose, consider a longer-
`term prescription of SUBOXONE to be taken at home. When determining the
`quantity of SUBOXONE to be prescribed, you should consider your patient’s level of
`stability, the security of his or her home situation, and other factors likely to affect the
`ability to manage supplies of medication in an unsupervised environment
`
`• Have plans in place to deal with patient requests for replacement of prescriptions or
`
`supplies of medication that are described as lost or stolen
`
`• Keep tight control of your prescription pads. Never leave them in the examination
`room, even inside a desk drawer. Never sign an incomplete prescription blank
`
`• Write all numbers (quantity and strength) in both numbers and letters - like you
`would write a personal check
`
`• Establish a relationship with the pharmacies you expect to be filling your
`prescriptions. Discuss potential diversion problems and controls with them
`
`• Maintain copies of photo (or other) I.D. and Social Security numbers in patients’
`records
`If you suspect an attempt to divert prescription medications, unsupervised
`administration privileges should be reevaluated. Carefully consider options such as
`random drug testing or a callback to verify adherence to program rules. In a callback,
`the patient receives an unannounced phone call and must show up at the physician’s
`office within a reasonable period (e.g., 24 to 36 hours) with all prescribed
`medications. In this case, the number of pouches remaining must correspond to the
`number expected based on prescribed dosing. If this program is implemented,
`physicians should clearly state their policy to patients in advance
`
`
`•
`
`Buprenorphine, like morphine and other opioids, has the potential for being abused and
`
`is subject to criminal diversion. Patients who continue to misuse, abuse, or divert
`buprenorphine products or other opioids should be provided or referred for more
`intensive and structured treatment.
`
`What is an appropriate medical response to overdose on SUBOXONE?
`In the case of overdose, the primary management should be the re-establishment of
`
`adequate ventilation with mechanical assistance of respiration, if required.
`
`Naloxone hydrochloride may be of value for the management of buprenorphine overdose.
`
`Higher than normal doses and repeated administration may be necessary.
`
`
`
`5
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`

`

`Contraindications
`
`Hypersensitivity to buprenorphine or naloxone
`
`Warnings and Precautions
`
`
`• Buprenorphine can be abused in a similar manner to other opioids. Clinical
`monitoring appropriate to the patient’s level of stability is essential. Multiple refills
`should not be prescribed early in treatment or without appropriate patient follow-up
`visits
`
`• Significant respiratory depression and death have occurred in association with
`buprenorphine, particularly when taken by the intravenous (IV) route in combination
`with benzodiazepines or other CNS depressants (including alcohol)
`
`• Consider dose reduction of CNS depressants, SUBOXONE sublingual film, or both
`in situations of concomitant prescription
`
`• Store SUBOXONE sublingual film safely out of the sight and reach of children.
`Buprenorphine can cause severe, possibly fatal, respiratory depression in children
`
`• Chronic administration produces opioid-type physical dependence. Abrupt
`discontinuation or rapid dose taper may result in opioid withdrawal syndrome
`
`• Monitor liver function tests prior to initiation and during treatment and evaluate
`suspected hepatic events
`
`• Do not administer SUBOXONE sublingual film to patients with known
`hypersensitivity to buprenorphine or naloxone
`
`• A marked and intense opioid withdrawal syndrome is highly likely to occur with
`parenteral misuse of SUBOXONE sublingual film by individuals physically
`dependent on full opioid agonists or by sublingual administration before the agonist
`effects of other opioids have subsided
`
`• Neonatal withdrawal has been reported following use of buprenorphine by the mother
`during pregnancy
`
`• SUBOXONE sublingual film is not appropriate as an analgesic. There have been
`reported deaths of opioid naïve individuals who received a 2 mg sublingual dose
`
`•