BUNAVAIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUNAVAIL (BUNAVAIL).
Buprenorphine is a partial mu-opioid receptor agonist and a weak kappa-opioid receptor antagonist; naloxone is a mu-opioid receptor antagonist that prevents misuse via injection.
| Metabolism | Buprenorphine is primarily metabolized via N-dealkylation by CYP3A4 to norbuprenorphine; also undergoes glucuronidation. Naloxone undergoes hepatic metabolism primarily by glucuronidation. |
| Excretion | Fecal (~70%) as unconjugated buprenorphine and metabolites; renal (~30%) primarily as conjugated metabolites. |
| Half-life | Terminal elimination half-life of buprenorphine is approximately 24-42 hours (mean ~37 hours) due to slow dissociation from mu-opioid receptors, supporting extended dosing intervals. |
| Protein binding | Approximately 96% bound to alpha- and beta-globulins, not significantly to albumin. |
| Volume of Distribution | Vd: 2.5-4.0 L/kg, indicating extensive tissue distribution and high lipophilicity. |
| Bioavailability | Buccal: ~30-40% relative to intravenous; sublingual: ~30% due to first-pass metabolism; buccal route avoids some gastrointestinal degradation. |
| Onset of Action | Buccal: 30-60 minutes for clinically meaningful analgesia; sublingual: 30-60 minutes for rapid relief. |
| Duration of Action | Buprenorphine provides analgesia for 6-8 hours after buccal administration; however, opioid blockade for abuse deterrence persists for 24-48 hours due to long receptor occupancy. |
| Molecular Weight | 467.6 Da |
For moderate to severe opioid use disorder: sublingual film, induction: 2-4 mg buprenorphine/0.5-1 mg naloxone on day 1, then up to 8 mg/2 mg on day 2; maintenance: target 16 mg/4 mg sublingually once daily, range 4-24 mg/1-6 mg daily.
| Dosage form | FILM |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl < 30 mL/min): use with caution; consider dose reduction or extended intervals due to potential accumulation of buprenorphine. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B): reduce starting dose by 50% and titrate slowly. For mild impairment (Child-Pugh class A): no dose adjustment required. |
| Pediatric use | Not approved for patients under 16 years; safety and efficacy not established. For adolescents 16 years and older: use adult dosing based on weight and severity. |
| Geriatric use | No specific dose adjustment in elderly; use caution due to increased sensitivity, impaired hepatic/renal function, and risk of falls. Start at low end of dosing range and titrate slowly. |
| 1st trimester | Buprenorphine is used for opioid use disorder during pregnancy; limited data show no increased risk of malformations. However, use only if potential benefit justifies risk. |
| 2nd trimester | Same as t1; monitor for withdrawal in neonate. |
| 3rd trimester | Use may lead to neonatal opioid withdrawal syndrome; monitor newborn closely. |
Clinical note
Comprehensive clinical and safety monograph for BUNAVAIL (BUNAVAIL).
| Placental transfer | Buprenorphine crosses the placenta; fetal exposure is significant, with fetal/maternal ratio approximately 0.4-0.6. |
| Breastfeeding | Buprenorphine is excreted into breast milk in low concentrations. The American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for sedation and feeding difficulties. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; respiratory depression and death with IV administration; neonatal opioid withdrawal syndrome with prolonged use; risk of opioid withdrawal with abrupt discontinuation; risk of hepatitis, hepatic events; precipitation of withdrawal if given to patients dependent on full agonists.
| Serious Effects |
Hypersensitivity to buprenorphineSevere respiratory insufficiencySevere hepatic impairment
| Precautions | Respiratory depression; neonatal opioid withdrawal syndrome; hepatic injury; precipitation of opioid withdrawal; risks from concomitant use with benzodiazepines or CNS depressants; dependence and withdrawal; use in patients with compromised respiratory function; increased intracranial pressure; hypotension; biliary tract disease; QT prolongation; impairment of driving/operating machinery. |
| Food/Dietary | No significant food interactions. However, patients should avoid grapefruit juice as it may increase buprenorphine levels. Advise to take on an empty stomach for consistent absorption, though food does not significantly alter bioavailability. |
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| Lactation Rating |
| L2 (Probably Compatible) |
| Teratogenic Risk | Buprenorphine, a component of BUNAVAIL, is not associated with major congenital malformations. However, third-trimester use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Use in pregnancy only if benefit outweighs risk. |
| Fetal Monitoring | Monitor for maternal sedation, respiratory depression, and signs of opioid withdrawal. Fetal monitoring should include nonstress test and biophysical profile as clinically indicated. Assess for neonatal withdrawal after delivery. |
| Fertility Effects | Buprenorphine may impair male and female fertility by altering hormonal regulation. Effects are reversible upon discontinuation. |
| Clinical Pearls | BUNAVAIL (buprenorphine/naloxone) sublingual film is indicated for maintenance treatment of opioid dependence. Administer as a single daily dose; films can be cut to achieve lower doses. Avoid abrupt discontinuation to prevent withdrawal. Monitor for respiratory depression, especially during induction. Use with caution in patients with hepatic impairment; naloxone component may precipitate withdrawal in opioid-tolerant patients if injected. |
| Patient Advice | Place the film under the tongue and allow it to dissolve completely; do not chew, swallow, or move the film after placement. · Do not drink or eat until the film has completely dissolved. · Avoid use of alcohol or other central nervous system depressants (e.g., benzodiazepines) while taking this medication as it may increase risk of respiratory depression. · Do not stop taking this medication suddenly without consulting your healthcare provider as withdrawal symptoms may occur. · Store at room temperature away from moisture and heat; keep out of reach of children. · This medication can cause drowsiness; avoid driving or operating heavy machinery until you know how it affects you. · Inform all healthcare providers that you are taking this medication before any surgery or emergency treatment. · Do not take other opioids, including illicit drugs, while on this medication as it may cause severe withdrawal or overdose. |