Dosage and Administration, Induction (2.1)
               04/2014

Dosage and Administration, Patients With
       Hepatic Impairment (2.5)
               04/2014

Warnings and Precautions, Use in Patients

       With Impaired Hepatic Function (5.11)
               04/2014

SUBOXONE sublingual film is a partial-opioid agonist indicated for treatment of opioid dependence. Prescription use of this product is limited under the Drug Addiction Treatment Act. (1)
DOSAGE AND ADMINISTRATION

• For patients dependent on short-acting opioid products who are in opioid withdrawal; on Day 1, administer up to 8 mg/ 2 mg SUBOXONE sublingual film (in divided doses). On Day 2, administer up to 16 mg/4 mg of SUBOXONE sublingual film as a single dose. (2.1)
• For patients dependent on methadone or long-acting opioid products, induction onto sublingual buprenorphine monotherapy is recommended on Days 1 and 2 of treatment. (2.1)
• For maintenance treatment, the target dosage of SUBOXONE sublingual film is usually 16 mg/4 mg as a single daily dose. (2.2)
• Place the SUBOXONE sublingual film under the tongue, close to the base on the left or right side and allow to completely dissolve. Film should not be chewed, swallowed, or moved after placement. (2.3)

Sublingual film: 2 mg buprenorphine with 0.5 mg naloxone, 4 mg buprenorphine with 1 mg naloxone, 8 mg buprenorphine with 2 mg naloxone and 12 mg buprenorphine with 3 mg naloxone. (3)
CONTRAINDICATIONS

Hypersensitivity to buprenorphine or naloxone. (4)
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. (5.1)
• 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). (5.2)
• Consider dose reduction of CNS depressants, SUBOXONE sublingual film, or both in situations of concomitant prescription. (5.3)
• Store SUBOXONE sublingual film safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. (5.4)
• Chronic administration produces opioid-type physical dependence. Abrupt discontinuation or rapid dose taper may result in opioid withdrawal syndrome. (5.5)
• Monitor liver function tests prior to initiation and during treatment and eva luate suspected hepatic events. (5.6)
• Do not administer SUBOXONE sublingual film to patients with known hypersensitivity to buprenorphine or naloxone. (5.7)
• An opioid withdrawal syndrome is 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. (5.8)
• Neonatal withdrawal has been reported following use of buprenorphine by the mother during pregnancy. (5.9)
• 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. (5.10)
• Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment (5.11)
• Caution patients about the risk of driving or operating hazardous machinery. (5.12)

Adverse events commonly observed with the sublingual administration of the SUBOXONE sublingual film were oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Reckitt Benckiser Pharmaceuticals Inc. at 1-877-782-6966 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing. (7.1)
• Use caution in prescribing SUBOXONE sublingual film for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse. (7.3)

• Pregnancy: Based on animal data, may cause fetal harm. (8.1)
• Nursing mothers: Caution should be exercised when administered to a nursing woman. (8.3)
• Safety and effectiveness of SUBOXONE sublingual film in patients below the age of 16 has not been established. (8.4)
• Administer SUBOXONE sublingual film with caution to elderly or debilitated patients. (8.5)
• Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. (8.6)