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`HIGHLIGHTS OF PRESCRIBING INFORMATION
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`These highlights do not include all the information needed to use
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`SUBOXONE safely and effectively. See full prescribing information for
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`SUBOXONE.
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`SUBOXONE® (buprenorphine and naloxone) sublingual film, for sublingual
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`or buccal use CIII
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`Initial U.S. Approval: 2002
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐RECENT MAJOR CHANGES‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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`Warnings and Precautions, Neonatal Opioid
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`Withdrawal Syndrome (5.5)
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`Warnings and Precautions,
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`Aderenal Insufficiency (5.7)
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`12/2016
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`12/2016
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐INDICATIONS AND USAGE‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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`SUBOXONE (buprenorphine and naloxone) sublingual film is a partial‐opioid
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`agonist indicated for treatment of opioid dependence. Prescription use of
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`this product is limited under the Drug Addiction Treatment Act. (1)
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐DOSAGE AND ADMINISTRATION‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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` For patients dependent on short‐acting opioid products who are in opioid
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`withdrawal; on Day 1, administer up to 8 mg/2 mg SUBOXONE sublingual
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`film (in divided doses). On Day 2, administer up to 16 mg/4 mg of
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`SUBOXONE sublingual film as a single dose. (2.1)
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` For patients dependent on methadone or long‐acting opioid products,
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`induction onto sublingual buprenorphine monotherapy is recommended
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`on Days 1 and 2 of treatment. (2.1)
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` For maintenance treatment, the target dosage of SUBOXONE sublingual
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`film is usually 16 mg/4 mg as a single daily dose. (2.2)
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` Sublingual Administration: Place one film under the tongue, close to the
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`base on the left or right side, and allow to completely dissolve.
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`Buccal Administration: Place one film on the inside of the left or right
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`cheek and allow to completely dissolve.
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` SUBOXONE sublingual film must be administered whole. Do not cut,
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`chew, or swallow SUBOXONE sublingual film (2.3)
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐DOSAGE FORMS AND STRENGTHS‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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`Sublingual film: 2 mg buprenorphine with 0.5 mg naloxone,
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`4 mg buprenorphine with 1 mg naloxone, 8 mg buprenorphine with
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`2 mg naloxone and 12 mg buprenorphine with 3 mg naloxone. (3)
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`Hypersensitivity to buprenorphine or naloxone. (4)
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐WARNINGS AND PRECAUTIONS‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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` Buprenorphine can be abused in a similar manner to other opioids.
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`Clinical monitoring appropriate to the patient’s level of stability is
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`essential. Multiple refills should not be prescribed early in treatment or
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`without appropriate patient follow‐up visits. (5.1)
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` Significant respiratory depression and death have occurred in association
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`with buprenorphine, particularly when taken by the intravenous (IV)
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`route in combination with benzodiazepines or other CNS depressants
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`(including alcohol). (5.2)
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` Consider dose reduction of CNS depressants, SUBOXONE sublingual film,
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`or both in situations of concomitant prescription. (5.3)
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` Store SUBOXONE sublingual film safely out of the sight and reach of
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`children. Buprenorphine can cause severe, possibly fatal, respiratory
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`depression in children. (5.4)
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`Reference ID: 4055394
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` Neonatal opioid withdrawal syndrome (NOWS) is an expected and
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`treatable outcome of prolonged use of opioids during pregnancy (5.5)
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` Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of
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`corticosteroids, and wean patient off of the opioid. (5.6)
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` Chronic administration produces opioid‐type physical dependence.
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`Abrupt discontinuation or rapid dose taper may result in opioid
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`withdrawal syndrome. (5.7)
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` Monitor liver function tests prior to initiation and during treatment and
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`evaluate suspected hepatic events. (5.8)
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` Do not administer SUBOXONE sublingual film to patients with known
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`hypersensitivity to buprenorphine or naloxone. (5.9)
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` An opioid withdrawal syndrome is likely to occur with parenteral misuse
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`of SUBOXONE sublingual film by individuals physically dependent on full
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`opioid agonists, or by sublingual or buccal administration before the
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`agonist effects of other opioids have subsided. (5.10)
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` SUBOXONE sublingual film is not appropriate as an analgesic. There have
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`been reported deaths of opioid naïve individuals who received a 2 mg
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`sublingual dose. (5.11)
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` Buprenorphine/naloxone products are not recommended in patients
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`with severe hepatic impairment and may not be appropriate for patients
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`with moderate hepatic impairment (5.12)
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` Caution patients about the risk of driving or operating hazardous
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`machinery. (5.13)
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ADVERSE REACTIONS‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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`Adverse events commonly observed with the sublingual/buccal
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`administration of the SUBOXONE sublingual film were oral hypoesthesia,
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`glossodynia, oral mucosal erythema, headache, nausea, vomiting,
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`hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia,
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`pain, and peripheral edema. (6.1)
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`To report SUSPECTED ADVERSE REACTIONS, contact Indivior Inc. at 1‐877‐
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`782‐6966 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.
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`‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐DRUG INTERACTIONS‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
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` Use caution in prescribing SUBOXONE sublingual film for patients
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`receiving benzodiazepines or other CNS depressants and warn patients
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`against concomitant self‐administration/misuse. (7)
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` Monitor patients starting or ending CYP3A4 inhibitors or inducers for
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`potential over or under dosing. (7)
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` Patients who are on chronic buprenorphine treatment should have their
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`dose monitored if NNRTIs are added to their treatment regimen.
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`Monitor patients taking buprenorphine and atazanavir with and without
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`ritonavir, and dose reduction of buprenorphine may be warranted. (7)
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` Serotonergic Drugs: Concomitant use may result in serotonin syndrome.
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`Discontinue SUBOXONE sublingual film if serotonin syndrome is
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`Nursing mothers: Caution should be exercised when administered to a
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`nursing woman. (8.2)
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`Safety and effectiveness of SUBOXONE sublingual film in patients below
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`the age of 16 has not been established. (8.4)
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`Administer SUBOXONE sublingual film with caution to elderly or
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`debilitated patients. (8.5)
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`Buprenorphine/naloxone products are not recommended in patients
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`with severe hepatic impairment and may not be appropriate for
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`patients with moderate hepatic impairment. (8.6)
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`See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
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`Revised: 02/2017
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` 7
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`8
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`9
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`11
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`12
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`17
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` DRUG INTERACTIONS
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`USE IN SPECIFIC POPULATIONS
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`8.1
`Pregnancy
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`8.2
`Lactation
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`8.3
`Female and Males Reproductive Potential
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`8.4
`Pediatric Use
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`8.5 Geriatric Use
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`8.6 Hepatic Impairment
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`8.7
`Renal Impairment
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`DRUG ABUSE AND DEPENDENCE
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`9.1
`Controlled Substance
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`9.2
`Abuse
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`9.3 Dependence
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`OVERDOSAGE
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`DESCRIPTION
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`CLINICAL PHARMACOLOGY
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`12.1 Mechanism of Action
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`12.2 Pharmacodynamics
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`12.3 Pharmacokinetics
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`NONCLINICAL TOXICOLOGY
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`13.1 Carcinogenesis, Mutagenesis, Impairment of
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`Fertility
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`HOW SUPPLIED / STORAGE AND HANDLING
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`PATIENT COUNSELING INFORMATION
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`Safe Use
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`Disposal of Unused SUBOXONE Sublingual Films
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`Sections and subsections omitted from the full
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`prescribing information are not listed.
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` FULL PRESCRIBING INFORMATION: CONTENTS*
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` 1
` INDICATIONS AND USAGE
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` 2
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` DOSAGE AND ADMINISTRATION
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` Induction
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` 2.1
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` 2.2 Maintenance
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` 2.3 Method of Administration
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` 2.4
` Clinical Supervision
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` 2.5
` Patients With Hepatic Impairment
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` 2.6 Unstable Patients
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` 2.7
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` Stopping Treatment
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` 2.8
` Switching Between Buprenorphine and
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` Sublingual Film
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` Switching Between SUBOXONE Sublingual Film
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` Strengths
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` 2.10 Switching Between Sublingual and Buccal Sites
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` of Administration
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` DOSAGE FORMS AND STRENGTHS
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` CONTRAINDICATIONS
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` WARNINGS AND PRECAUTIONS
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` Abuse Potential
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` 5.1
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` 5.2
` Respiratory Depression
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` 5.3
` CNS Depression
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` 5.4 Unintentional Pediatric Exposure
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` 5.5 Neonatal Opioid Withdrawal Syndrome
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` 5.6
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` Adrenal Insufficiency
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` 5.7 Dependence
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` 5.8 Hepatitis, Hepatic Events
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` 5.9
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` Allergic Reactions
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` 5.10 Precipitation of Opioid Withdrawal Signs and
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` 5.11 Use in Opioid Naïve Patients
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` 5.12 Use in Patients With Impaired Hepatic Function
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` 5.13
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` Impairment of Ability to Drive or Operate
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` Machinery
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` 5.14 Orthostatic Hypotension
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` 5.15 Elevation of Cerebrospinal Fluid Pressure
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` 5.16 Elevation of Intracholedochal Pressure
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` 5.17 Effects in Acute Abdominal Conditions
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` 5.18 General Precautions
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` ADVERSE REACTIONS
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` 6.1
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` Clinical Trials Experience
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` 6.2
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` Postmarketing Experience
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` 2.9
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` 3
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` 4
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` 5
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` 6
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`Reference ID: 4055394
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`DOSAGE AND ADMINISTRATION
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` FULL PRESCRIBING INFORMATION
`
` INDICATIONS AND USAGE
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` 1
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` SUBOXONE (buprenorphine and naloxone) sublingual film is indicated for treatment of opioid dependence and
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` should be used as part of a complete treatment plan to include counseling and psychosocial support.
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` Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in
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`the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying
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`requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to
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`prescribe this product for the treatment of opioid dependence and have been assigned a unique identification
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`number that must be included on every prescription.
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`2
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`Induction
`2.1
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`Prior to induction, consideration should be given to the type of opioid dependence (i.e., long‐ or short‐acting
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`opioid products), the time since last opioid use, and the degree or level of opioid dependence. To avoid
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`precipitating an opioid withdrawal syndrome, the first dose of buprenorphine/naloxone should be started only
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`when objective signs of moderate withdrawal appear.
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`On Day 1, an induction dosage of up to 8 mg/2 mg SUBOXONE sublingual film is recommended. Clinicians
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`should start with an initial dose of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone and may titrate
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`upwards in 2 or 4 mg increments of buprenorphine, at approximately 2‐hour intervals, under supervision, to 8
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`mg/2 mg buprenorphine/naloxone based on the control of acute withdrawal symptoms.
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`On Day 2, a single daily dose of up to 16 mg/4 mg SUBOXONE sublingual film is recommended.
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`Because the exposure to naloxone is somewhat higher after buccal than after sublingual administration, it is
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`recommended that the sublingual site of administration be used during induction to minimize exposure to
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`naloxone, to reduce the risk of precipitated withdrawal.
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`Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not
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`advised early in treatment or without appropriate patient follow‐up visits.
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`Patients dependent on methadone or long‐acting opioid products
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`Patients dependent upon methadone or long‐acting opioid products may be more susceptible to precipitated
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`and prolonged withdrawal during induction than those on short‐acting opioid products.
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`Buprenorphine/naloxone combination products have not been evaluated in adequate and well‐controlled
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`studies for induction in patients on long‐acting opioid products, and contain naloxone, which is absorbed in
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`small amounts by the sublingual route and could cause worse precipitated and prolonged withdrawal. For this
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`reason, buprenorphine monotherapy is recommended in patients taking long‐acting opioids when used
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`according to approved administration instructions. Following induction, the patient may then be transitioned
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`to once‐daily SUBOXONE sublingual film.
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`Patients dependent on heroin or other short‐acting opioid products
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`Patients dependent on heroin or short‐acting opioid products may be inducted with either SUBOXONE sublingual
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`film or with sublingual buprenorphine monotherapy. The first dose of SUBOXONE sublingual film or
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`buprenorphine should be administered when objective signs of moderate opioid withdrawal appear, and not less
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`than 6 hours after the patient last used an opioid.
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`It is recommended that an adequate maintenance dose, titrated to clinical effectiveness, be achieved as rapidly
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`as possible. In some studies, a too‐gradual induction over several days led to a high rate of drop‐out of
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`buprenorphine patients during the induction period.
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`Reference ID: 4055394
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` Maintenance
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` 2.2
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` For maintenance, SUBOXONE sublingual film may be administered buccally or sublingually. The dosage of
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` SUBOXONE sublingual film from Day 3 onwards should be progressively adjusted in increments/decrements of 2
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` mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses
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` opioid withdrawal signs and symptoms.
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` After treatment induction and stabilization, the maintenance dose of SUBOXONE sublingual film is generally in
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` the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day depending on
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` the individual patient and clinical response. The recommended target dosage of SUBOXONE sublingual film
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` during maintenance is 16 mg/4 mg buprenorphine/naloxone/day as a single daily dose. Dosages higher than 24
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` mg/6 mg daily have not been demonstrated to provide a clinical advantage.
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` When determining the prescription quantity for unsupervised administration, consider the patient’s level of
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` stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies
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` of take‐home medication.
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`2.3 Method of Administration
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`SUBOXONE sublingual film must be administered whole. Do not cut, chew, or swallow SUBOXONE sublingual
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`film.
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`Sublingual Administration
`Place one film under the tongue, close to the base on the left or right side. If an additional film is necessary to
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`achieve the prescribed dose, place an additional film sublingually on the opposite side from the first film. Place
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`the film in a manner to minimize overlapping as much as possible. The film must be kept under the tongue until
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`the film is completely dissolved. If a third film is necessary to achieve the prescribed dose, place it under the
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`tongue on either side after the first 2 films have dissolved.
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`Buccal Administration
`Place one film on the inside of the right or left cheek. If an additional film is necessary to achieve the prescribed
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`dose, place an additional film on the inside of the opposite cheek. The film must be kept on the inside of the
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`cheek until the film is completely dissolved. If a third film is necessary to achieve the prescribed dose, place it on
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`the inside of the right or left cheek after the first two films have dissolved.
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`SUBOXONE sublingual film should NOT be moved after placement. Proper administration technique should be
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`demonstrated to the patient.
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`Clinical Supervision
`2.4
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`Treatment should be initiated with supervised administration, progressing to unsupervised administration as
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`the patient’s clinical stability permits. SUBOXONE sublingual film is subject to diversion and abuse. When
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`determining the prescription quantity for unsupervised administration, consider the patient’s level of stability,
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`the security of his or her home situation, and other factors likely to affect the ability to manage supplies of
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`take‐home medication.
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`Ideally patients should be seen at reasonable intervals (e.g., at least weekly during the first month of
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`treatment) based upon the individual circumstances of the patient. Medication should be prescribed in
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`consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without
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`appropriate patient follow‐up visits. Periodic assessment is necessary to determine compliance with the dosing
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`regimen, effectiveness of the treatment plan, and overall patient progress.
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`Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate
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`illicit drug use, less frequent follow‐up visits may be appropriate. A once‐monthly visit schedule may be
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`reasonable for patients on a stable dosage of medication who are making progress toward their treatment
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`objectives. Continuation or modification of pharmacotherapy should be based on the healthcare provider’s
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`evaluation of treatment outcomes and objectives such as:
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`Reference ID: 4055394
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`1. Absence of medication toxicity.
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`2. Absence of medical or behavioral adverse effects.
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`3. Responsible handling of medications by the patient.
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`4. Patient’s compliance with all elements of the treatment plan (including recovery‐oriented activities,
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`psychotherapy, and/or other psychosocial modalities).
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`5. Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use).
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`If treatment goals are not being achieved, the healthcare provider should re‐evaluate the appropriateness of
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`continuing the current treatment.
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`Patients With Hepatic Impairment
`2.5
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`Severe hepatic impairment results in a reduced clearance of naloxone to a much greater extent than
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`buprenorphine, and moderate hepatic impairment also results in a reduced clearance of naloxone to a greater
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`extent than buprenorphine. Because the doses of this fixed combination product cannot be individually
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`titrated, the combination product should generally be avoided in patients with severe hepatic impairment and
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`may not be appropriate for patients with moderate hepatic impairment [see Warnings and Precautions (5.12)].
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`Unstable Patients
`2.6
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`Healthcare providers will need to decide when they cannot appropriately provide further management for
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`particular patients. For example, some patients may be abusing or dependent on various drugs, or
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`unresponsive to psychosocial intervention such that the healthcare provider does not feel that he/she has the
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`expertise to manage the patient. In such cases, the healthcare provider may want to assess whether to refer
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`the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on
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`a treatment plan established and agreed upon with the patient at the beginning of treatment.
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`Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided
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`with, or referred to, more intensive and structured treatment.
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` 2.7
` Stopping Treatment
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` The decision to discontinue therapy with SUBOXONE sublingual film after a period of maintenance should be
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` made as part of a comprehensive treatment plan. Taper patients to avoid opioid withdrawal signs and
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` symptoms.
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`Switching Between Buprenorphine or Buprenorphine and Naloxone Sublingual Tablets and
`2.8
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`SUBOXONE Sublingual Film
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`Patients being switched between buprenorphine and naloxone or buprenorphine only sublingual tablets and
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`SUBOXONE sublingual film should be started on the corresponding dosage of the previously administered
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`product. However, dosage adjustments may be necessary when switching between buprenorphine products.
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`Not all strengths and combinations of the SUBOXONE sublingual films are bioequivalent to the SUBOXONE
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`(buprenorphine and naloxone) sublingual tablets as observed in pharmacokinetic studies [see Clinical
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`Pharmacology (12.3)]. Therefore, systemic exposures of buprenorphine and naloxone may be different when
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`patients are switched from tablets to film or vice‐versa. Patients should be monitored for symptoms related to
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`over‐dosing or under‐dosing.
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`Switching Between SUBOXONE Sublingual Film Strengths
`2.9
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`As indicated in Table 1, the sizes and the compositions of the four units of SUBOXONE sublingual films, i.e.,
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`Reference ID: 4055394
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` 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg and the 12 mg/3 mg units, are different from one another. If patients
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` switch between various combinations of lower and higher strength units of SUBOXONE sublingual films to
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` obtain the same total dose, (e.g., from three 4 mg/1 mg units to a single 12 mg/3 mg unit, or vice‐versa),
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` systemic exposures of buprenorphine and naloxone may be different and patients should be monitored for
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` over‐dosing or under‐dosing. For this reason, pharmacist should not substitute one or more film strengths for
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` another without approval of the prescriber.
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`Table 1. Comparison of Available SUBOXONE Sublingual Film Strengths by Dimensions and Drug
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`Concentrations.
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`SUBOXONE sublingual film unit strength
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`(buprenorphine/naloxone)
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`SUBOXONE sublingual
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`film unit dimensions
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`2 mg/0.5 mg
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`22.0 mm x 12.8 mm
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`Buprenorphine
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`Concentration
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`% (w/w)
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`5.4
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`Naloxone
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`Concentration
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`% (w/w)
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`1.53
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`4 mg/1 mg
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`(2 times the length of the 2 mg/0.5 mg unit)
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`22.0 mm x 25.6 mm
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`5.4
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`8 mg/2 mg
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`22.0 mm x 12.8 mm
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`17.2
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`12 mg/3 mg
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`(1.5 times the length of the 8 mg/2 mg unit)
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`22.0 mm X 19.2 mm
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`17.2
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`1.53
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`4.88
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`4.88
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`2.10 Switching Between Sublingual and Buccal Sites of Administration
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`The systemic exposure of buprenorphine between buccal and sublingual administration of SUBOXONE
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`sublingual film is similar. Therefore, once induction is complete, patients can switch between buccal and
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`sublingual administration without significant risk of under or overdosing.
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`DOSAGE FORMS AND STRENGTHS
`3
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`SUBOXONE sublingual film is supplied as an orange rectangular film with a white printed logo in four dosage
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`strengths:
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` buprenorphine/naloxone 2 mg/0.5 mg,
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` buprenorphine/naloxone 4 mg/1 mg,
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` buprenorphine/naloxone 8 mg/2 mg and
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` buprenorphine/naloxone 12 mg/3 mg
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`CONTRAINDICATIONS
`4
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`SUBOXONE sublingual film should not be administered to patients who have been shown to be hypersensitive
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`to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported
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`[see Warnings and Precautions (5.9)].
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`Reference ID: 4055394
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`WARNINGS AND PRECAUTIONS
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`5
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`Abuse Potential
`5.1
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`Buprenorphine can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense
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`buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure
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`appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient’s level
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`of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate
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`patient follow‐up visits [see Drug Abuse and Dependence (9.2)].
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`Respiratory Depression
`5.2
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`Buprenorphine, particularly when taken by the IV route, in combination with benzodiazepines or other CNS
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`depressants (including alcohol), has been associated with significant respiratory depression and death. Many,
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`but not all, post‐marketing reports regarding coma and death associated with the concomitant use of
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`buprenorphine and benzodiazepines involved misuse by self‐injection. Deaths have also been reported in
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`association with concomitant administration of buprenorphine with other depressants such as alcohol or other
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`CNS depressant drugs. Patients should be warned of the potential danger of self‐administration of
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`benzodiazepines or other depressants while under treatment with SUBOXONE sublingual film [see Drug
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`Interactions (7)].
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`In the case of overdose, the primary management should be the re‐establishment of adequate ventilation with
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`mechanical assistance of respiration, if required. Naloxone may be of value for the management of
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`buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.
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`SUBOXONE sublingual film should be used with caution in patients with compromised respiratory function
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`(e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia,
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`hypercapnia, or pre‐existing respiratory depression).
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`CNS Depression
`5.3
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`Patients receiving buprenorphine in the presence of opioid analgesics, general anesthetics, benzodiazepines,
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`phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) may
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`exhibit increased CNS depression. Consider dose reduction of CNS depressants, SUBOXONE sublingual film, or
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`both in situations of concomitant prescription [see Drug Interactions (7)].
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`Unintentional Pediatric Exposure
`5.4
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`Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally
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`exposed to it. Store buprenorphine‐containing medications safely out of the sight and reach of children.
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`Neonatal Opioid Withdrawal Syndrome
`5.5
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`Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of
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`opioids during pregnancy, whether that use is medically‐authorized or illicit. Unlike opioid withdrawal
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`syndrome in adults, NOWS may be life‐threatening if not recognized and treated in the neonate. Healthcare
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`professionals should observe newborns for signs of NOWS and manage accordingly [see Use in Specific
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`Populations (8.1)].
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