both in vivo and in vitro incorporation of [3H]thymidine, and positive in unscheduled DNA synthesis (UDS) test using testicular cells from mice.
Impairment of Fertility:
Dietary administration of buprenorphine in the rat at dose levels of 500 ppm or greater (equivalent to approximately 47 mg/kg/day or greater; estimated exposure approximately 28 times the RHD) produced a reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 100 ppm (equivalent to approximately 10 mg/kg/day; estimated exposure approximately 6 times the RHD) had no adverse effect on fertility.
16 HOW SUPPLIED/STORAGE AND HANDLING
BUNAVAIL is supplied in individually-sealed foil packages. BUNAVAIL is supplied in three dosage strengths. Each unit is individually wrapped in a child resistant foil package. These foil packages are packed 30 per box.
Each dosage unit is a yellow, rectangular film, with a dosage marking printed on the mucoadhesive side. The dosage strength of each unit is indicated by the dosage marking on the mucoadhesive side of the dose unit, and the dosage strength is marked on the foil package and the 30-unit box. See package and carton for product information.
Store at 20-25°C (68-77°F), with excursions permitted between 15-30°C (59°F-86°F) until ready to use. Protect BUNAVAIL from freezing and moisture. Do not use if the foil package has been damaged.
Patients should be advised to store buprenorphine-containing medications safely and out of sight and reach of children. Destroy any unused medication appropriately [see Patient Counseling Information (17.2)].
Rx only
17 PATIENT COUNSELING INFORMATION
See FDA approved patient labeling (Medication Guide).
17.1 Safe UseBefore initiating treatment with BUNAVAIL buccal film, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time BUNAVAIL is dispensed because new information may be available
Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines or other CNS depressants (including alcohol) while taking BUNAVAIL buccal films. Patients prescribed benzodiazepines or other CNS depressants should be cautioned to use them only as directed by their physician [see Warnings and Precautions (5.2), Drug Interactions (7.3)].
Patients should be advised that BUNAVAIL buccal films contain an opioid that can be a target for people who abuse prescription medications or street drugs. Patients should be cautioned to keep their films in a safe place, and to protect them from theft.
Patients should be instructed to keep BUNAVAIL buccal films 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 BUNAVAIL buccal films, medical attention should be sought immediately.
Patients should be advised never to give BUNAVAIL buccal films to anyone else, even if he or she has the same signs and symptoms. It may cause harm or death.
Patients should be advised that selling or giving away this medication is against the law.
Patients should be cautioned that BUNAVAIL buccal films may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving or operating machinery. Caution should be taken especially during drug induction
