Generic Name

Bunavail

Mechanism

• Buprenorphine:
• Partial agonist at the μ‑opioid receptor → provides analgesia and reduces withdrawal.
• High receptor affinity and slow dissociation maintain steady plasma concentrations, preventing withdrawal.
• Low intrinsic activity avoids ceiling effect for respiratory depression.
• Naloxone:
• Co‑formulated in a sublingual dose; negligible systemic absorption when taken as prescribed.
• Prevents diversion via injection: when injected, naloxone is rapidly absorbed, producing an opioid withdrawal crisis that discourages misuse.
• Low systemic absorption also minimizes opioid “sunk‐in” effect in users.

Pharmacokinetics

• Absorption
• Sublingual drainage gives ~55 % bioavailability for buprenorphine.
• Naloxone absorbed only when discarded or misused by injection.
• Distribution
• High plasma protein binding (~70 %).
• Central nervous system penetration adequate for receptor interaction.
• Metabolism
• Primarily via hepatic CYP3A4 → active metabolites.
• Minor contribution from CYP2C8.
• Elimination
• Half‑life ≈ 24–42 hr (buprenorphine); 5–7 hr (naloxone).
• Renally excreted metabolites; dose adjustment in severe renal impairment not usually needed.

Indications

Contraindications

• Contraindicated
• Known hypersensitivity to buprenorphine, naloxone, or excipients.
• Seizure disorder without adequate seizure control.
• Warnings
• Respiratory depression: always monitor CO₂ and oxygen saturation during initiation.
• Cardiotoxicity: QTc prolongation reported; avoid with anti‑arrhythmic drugs.
• Liver dysfunction: hepatic impairment may increase buprenorphine levels; dose adjustment may be necessary.
• Kidney disease: though no dose adjustment is typical, monitor for accumulation of metabolites in end‑stage renal disease.
• CNS depression & sedation: avoid concomitant GABAergic or CNS depressant agents.

Dosing

• Initial dose: 4 mg (4 mg buprenorphine + 2 mg naloxone) sublingually once daily.
• Titration:
• If withdrawal persists or if tolerance develops, increase by 4‑mg increments every 3–7 days.
• Maximum daily dose: 16 mg (8 mg buprenorphine + 4 mg naloxone).
• Administration:
• Place pill under the tongue and allow it to dissolve before swallowing.
• Do not chew, crush, or swallow intact tablets.
• Missed dose: Take as soon as remembered; do not double dose.

Adverse Effects

Monitoring

• Baseline:
• Liver function tests (ALT, AST, bilirubin).
• ECG (QTc).
• During Treatment:
• Monitor for withdrawal symptoms (COWS or COWS‑brief).
• Assess respiratory rate & O₂ sat on initiation days.
• Evaluate adherence and potential diversion.
• Periodic:
• Liver enzymes Q2–4 weeks.
• Emphasis on mental health status and social support.

Clinical Pearls

• Naloxone's Role: Even though naloxone is poorly absorbed sublingually, including it greatly discourages injection misuse; consider this a deterrence mechanism when counselling patients.
• Switching from Higher‑Dose Opioids: Initiate 1–2 days after cessation of full‑agonist opioids to reduce precipitated withdrawal; some clinicians start a microdose of buprenorphine before tapering.
• Cautions with Benzodiazepines: Avoid co‑administration, especially sips or rainy days; a coordination between sedation assessments and dose increases is crucial.
• Pregnancy & Lactation: Use under a pharmacologic advisory; limited data but considered acceptable if alternatives are contraindicated; mindful of fetal opioid exposure.
• Stability: Store at <25 °C; avoid moisture. A single dose can be removed from the pouch if used intermittently, but keep within the immediate time window to maintain potency.

Bottom line: *Bunavail* represents a key opioid stewardship tool—combining a high‑affinity partial agonist with an antagonist designed to curb diversion while maintaining efficacy. When used correctly, it reduces relapse risk and improves retention in addiction treatment programs.