N BEL UCA - purdue.ca

1 PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION NBELBUCA Buprenorphine Buccal Soluble Film 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg and 900 mcg of buprenorphine as buprenorphine hydrochloride. Opioid Analgesic Purdue Pharma 575 Granite Court Pickering, Ontario L1W 3W8 Date of Preparation: February 15, 2018 Submission Control No: 210011 BELBUCA is a registered trademark of BioDelivery Sciences International, Inc., used with permission by Purdue Pharma. BELBUCA Product Monograph Page 2 of 57 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ..3 SUMMARY PRODUCT INFORMATION ..3 INDICATIONS AND CLINICAL USE ..3 CONTRAINDICATIONS ..4 WARNINGS AND PRECAUTIONS ..4 ADVERSE REACTIONS ..17 DRUG INTERACTIONS ..22 DOSAGE AND ADMINISTRATION ..26 OVERDOSAGE ..31 ACTION AND CLINICAL PHARMACOLOGY ..32 STORAGE AND STABILITY ..35 SPECIAL HANDLING INSTRUCTIONS ..35 DOSAGE FORMS, COMPOSITION AND PACKAGING ..35 PART II: SCIENTIFIC INFORMATION.

2 37 PHARMACEUTICAL INFORMATION ..37 CLINICAL TRIALS ..38 DETAILED PHARMACOLOGY ..41 TOXICOLOGY ..41 REFERENCES ..43 PART III: PATIENT MEDICATION INFORMATION ..44 BELBUCA Product Monograph Page 3 of 57 NBELBUCA Buprenorphine Buccal Soluble Film 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg and 900 mcg of buprenorphine as buprenorphine hydrochloride. PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Administration Dosage Form / Strength Nonmedicinal Ingredients Oral Buccal soluble film Seven strengths with 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg and 900 mcg buprenorphine per film. Carboxymethylcellulose sodium, citric acid anhydrous, hydroxypropylcellulose, hydroxyethylcellulose, methylparaben, monobasic sodium phosphate, peppermint oil, polycarbophil, propylene glycol, propylparaben, saccharin sodium, sodium benzoate, sodium hydroxide, titanium dioxide, vitamin E acetate, yellow iron oxide, purified water and black ink (Shellac, black iron oxide) INDICATIONS AND CLINICAL USE Adults: BELBUCA (buprenorphine buccal soluble film) is indicated for the management of pain severe enough to require daily, continuous, long-term treatment and: that is opioid-responsive; and for which alternative options are inadequate.

3 BELBUCA is not indicated as an as-needed (PRN) analgesic. Geriatrics (> 65 years of age): Clinical trials conducted with BELBUCA did not identify any notable differences in pharmacokinetics in subjects aged of > 65 compared to younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease and other drug therapy. The dosage should be adjusted to the intensity of the pain and the sensitivity of the individual patient (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics). BELBUCA Product Monograph Page 4 of 57 Pediatrics (< 18 years of age): The safety and efficacy of BELBUCA have not been studied in the pediatric population. Therefore, use of BELBUCA is not indicated in patients under 18 years of age.

4 CONTRAINDICATIONS BELBUCA (buprenorphine buccal soluble film) is contraindicated in: Patients who are hypersensitive to the active substance (buprenorphine hydrochloride) or other opioid analgesics or to any ingredient in the formulation. For a complete listing, see the DOSAGE FORMS, COMPOSITION AND PACKAGING section of the Product Monograph. Patients with known or suspected oral mucositis Patients with mild pain Patients with intermittent or short duration pain The management of acute pain, including use in out-patient or day surgeries Patients with suspected surgical abdomen ( , acute appendicitis or pancreatitis) The management of peri-operative pain relief, or in other situations characterized by rapidly varying analgesic requirements Patients with acute asthma or other obstructive airway, and status asthmaticus Patients with acute respiratory depression, elevated carbon dioxide levels in the blood, and cor pulmonale Patients with acute alcoholism, or alcohol dependence, delirium tremens, and convulsive/ seizure disorders Patients with severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy)

5 Women who are pregnant, breast-feeding or during labour and delivery (see SERIOUS WARNINGS AND PRECAUTIONS and WARNINGS AND PRECAUTIONS) Opioid withdrawal and dependence substitution treatment Patients suffering from myasthenia gravis Patients with known or suspected mechanical gastrointestinal obstruction ( , bowel obstruction, strictures) or any diseases/conditions that affect bowel transit ( , ileus of any type) WARNINGS AND PRECAUTIONS BELBUCA Product Monograph Page 5 of 57 Serious Warnings and Precautions Limitations of Use Because of the risks of addiction, abuse , and misuse with opioids, even at recommended doses, which can lead to overdose and death, BELBUCA should only be used in patients for whom alternative treatment options ( , non-opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain (see DOSAGE AND ADMINISTRATION).

6 Addiction, abuse , and misuse : BELBUCA poses risks of opioid addiction, abuse , and misuse , which can lead to overdose and death. Each patient s risk should be assessed prior to prescribing BELBUCA, and all patients should be monitored regularly for the development of these behaviors or conditions (see WARNINGS AND PRECAUTIONS). BELBUCA should be stored securely to avoid theft or misuse . Life-threatening Respiratory Depression: OVERDOSE Serious, life-threatening, or fatal respiratory depression may occur with use of BELBUCA. Infants exposed in-utero or through breast milk are at risk of life-threatening respiratory depression upon delivery or when nursed. Patients should be monitored for respiratory depression, especially during initiation of BELBUCA or following a dose increase. misuse or abuse of BELBUCA by snorting or injecting buprenorphine extracted from BELBUCA film will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death (see WARNINGS AND PRECAUTIONS).

7 Further, instruct patients of the hazards related to taking opioids including fatal overdose. Accidental Exposure: Accidental consumption of even one dose of BELBUCA, especially by children, can result in a fatal overdose of buprenorphine (see DOSAGE AND ADMINISTRATION, Disposal, for instructions on proper disposal). Neonatal Opioid Withdrawal Syndrome: Prolonged maternal use of BELBUCA during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening (see WARNINGS AND PRECAUTIONS). Interaction with Alcohol: The co-ingestion of alcohol with BELBUCA should be avoided as it may result in dangerous addictive effects, causing serious injury or death (see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS). Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS AND PRECAUTIONS, Neurologic and DRUG INTERACTIONS).

8 Reserve concomitant prescribing of BELBUCA and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. BELBUCA Product Monograph Page 6 of 57 General Patients should be instructed not to give BELBUCA (buprenorphine buccal soluble film) to anyone other than the patient for whom it was prescribed; as such inappropriate use may have severe medical consequences, including death. BELBUCA should be stored securely to avoid theft or misuse . BELBUCA should ONLY be prescribed to patients who require continuous opioid treatment for pain management. Initiation doses higher than 75 mcg should not be used in opioid na ve patients (see DOSAGE AND ADMINISTRATION, Patients not receiving opioids at the time of initiation of BELBUCA treatment (opioid-na ve)).

9 BELBUCA should only be prescribed by persons knowledgeable in the continuous administration of potent opioids, in the management of patients receiving potent opioids for treatment of pain, and in the detection and management of respiratory depression, which includes the proper use of opioid receptor antagonists. As with other CNS depressants, patients who have received BELBUCA should be monitored especially for signs of respiratory depression until a stable maintenance dose is reached. BELBUCA film is intended for buccal use on intact oral mucosa only; use on areas of the mouth with any open sores or lesions can lead to an increase exposure to buprenorphine. Patients should be cautioned not to consume alcohol while using BELBUCA as it may increase the chance of experiencing serious adverse events, including death. Addiction, abuse and misuse : There is a potential risk of abuse and misuse with BELBUCA, as with all opioids, which can lead to overdose and death.

10 Therefore, BELBUCA should be prescribed and handled with caution. BELBUCA is intended for buccal mucosa use only. BELBUCA delivers the complete dose of buprenorphine when the film is fully dissolved in the mouth. Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse and abuse . Opioids, such as BELBUCA, should be used with particular care in patients with a history of alcohol and illicit/prescription drug abuse . However, concerns about abuse , addiction, and diversion should not prevent the proper management of pain. Opioids, such as BELBUCA, are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. This risk should be considered when prescribing or dispensing BELBUCA in situations where the healthcare professional is concerned about increased risk of misuse , abuse or diversion.