Introduction
Bunavail (buprenorphine and naloxone) buccal film is a medication-assisted treatment (MAT) product approved for the maintenance treatment of opioid use disorder (OUD). It combines a partial opioid agonist (buprenorphine) with an opioid antagonist (naloxone) in a unique buccal delivery system designed to reduce the potential for misuse and diversion while providing effective treatment for opioid dependence.
Mechanism of Action
Buprenorphine is a partial agonist at the mu-opioid receptor with high affinity and low intrinsic activity. It binds tightly to opioid receptors, displacing full opioid agonists while producing limited opioid effects, thereby reducing cravings and withdrawal symptoms without producing significant euphoria. Naloxone is included as an opioid antagonist that has minimal bioavailability when administered buccally as intended but will precipitate withdrawal if the product is misused by injection, serving as a deterrent to misuse.
Indications
- Maintenance treatment of opioid use disorder as part of a comprehensive treatment plan that includes counseling and psychosocial support
- FDA-approved for use in patients who have initiated treatment with a transmucosal buprenorphine product
Dosage and Administration
Initial dosing: Treatment should be initiated under medical supervision after patients have manifested clear signs of opioid withdrawal. The recommended starting dose is one 4.2 mg/0.7 mg buccal film once daily. Maintenance dosing: The target maintenance dose is one 8.4 mg/1.4 mg buccal film once daily. Dose adjustment should be made in increments or decrements of 2.1 mg/0.35 mg or 4.2 mg/0.7 mg buccal films to a level that maintains suppression of opioid withdrawal signs and symptoms. Administration technique: Apply film to the inside of the cheek (buccal mucosa) after moistening the application site. Do not chew or swallow the film. Place with pink side against cheek and hold in place for 5 seconds. Alternate sides of the mouth for subsequent applications. Special populations:- Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment
- Renal impairment: No dosage adjustment required
- Geriatric patients: Use caution due to increased sensitivity to opioids
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Buprenorphine reaches peak plasma concentrations in approximately 2.5-3 hours after buccal administration. Bioavailability is approximately 46-65% via the buccal route. Distribution: Buprenorphine is approximately 96% protein bound. Volume of distribution is large, indicating extensive tissue distribution. Metabolism: Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 via N-dealkylation to norbuprenorphine. Elimination: Terminal half-life of buprenorphine is approximately 26-42 hours. Excreted primarily in feces (approximately 70%) with renal elimination accounting for approximately 10-30%.Contraindications
- Hypersensitivity to buprenorphine, naloxone, or any component of the formulation
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
Warnings and Precautions
Addiction, abuse, and misuse: Bunavail contains buprenorphine, a Schedule III controlled substance with potential for abuse similar to other opioids. Respiratory depression: Life-threatening respiratory depression and death have occurred, particularly with concomitant benzodiazepine or other CNS depressant use. Hepatotoxicity: Cases of cytolytic hepatitis and hepatitis with jaundice have been reported. Precipitation of opioid withdrawal: May occur if administered to patients physically dependent on full opioid agonists. QT prolongation: Dose-related QTc interval prolongation has been observed. Neonatal opioid withdrawal syndrome: Prolonged use during pregnancy can result in neonatal withdrawal syndrome. Dental effects: Cases of dental caries, tooth loss, and other oral complications have been reported.Drug Interactions
CNS depressants: (e.g., benzodiazepines, alcohol, sedatives) - Increased risk of respiratory depression, profound sedation, coma, and death CYP3A4 inhibitors: (e.g., ketoconazole, ritonavir) - May increase buprenorphine levels CYP3A4 inducers: (e.g., rifampin, carbamazepine) - May decrease buprenorphine levels Serotonergic drugs: Risk of serotonin syndrome when used with other serotonergic agents Monoamine oxidase inhibitors (MAOIs): May potentiate opioid effectsAdverse Effects
Common adverse reactions (≥5%):- Headache (18%)
- Nausea (14%)
- Constipation (13%)
- Vomiting (8%)
- Fatigue (7%)
- Insomnia (7%)
- Sweating (6%)
- Application site reactions (15%)
- Respiratory depression
- Hepatotoxicity
- Allergic reactions
- Hypotension
- Adrenal insufficiency
- Androgen deficiency
Monitoring Parameters
- Treatment effectiveness: Reduction in opioid cravings, absence of withdrawal symptoms
- Misuse/diversion: Regular assessment for appropriate use
- Liver function: Baseline and periodic LFT monitoring
- Respiratory status: Especially during initiation and dose titration
- Mental status: Assessment for depression and suicidal ideation
- Dental health: Regular dental examinations
- ECG monitoring: In patients with cardiac risk factors or at higher doses
Patient Education
- Use exactly as prescribed; do not share with others
- Proper application technique: Place against inner cheek, not on tongue
- Do not stop abruptly due to risk of withdrawal symptoms
- Avoid alcohol and other CNS depressants
- Report any signs of allergic reaction, respiratory depression, or liver problems
- Maintain regular dental care and oral hygiene
- Store safely out of reach of children and others
- Dispose of properly to prevent accidental exposure
- Inform all healthcare providers about Bunavail use
- Understand that treatment is most effective when combined with counseling
References
1. FDA. (2014). Bunavail prescribing information. 2. Substance Abuse and Mental Health Services Administration. (2021). Medications for Opioid Use Disorder. Treatment Improvement Protocol 63. 3. Ling W, et al. (2011). Buprenorphine implants for treatment of opioid dependence: randomized controlled trial. JAMA, 304(14), 1576-1583. 4. Strain EC, et al. (2011). Opioid use disorder: treatment and management. In: Principles of Addiction Medicine, 5th edition. 5. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. 6. American Society of Addiction Medicine. (2020). The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder. 7. Drug Enforcement Administration. (2022). Controlled Substances Act. 8. World Health Organization. (2018). Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence.