Buprenorphine

1. Indications
   1. Pain management (intravenous Buprenorphine)
   2. Opioid Addiction (e.g. Heroin addiction)
      1. Alternative to low dose Methadone
      2. Prescribing requires FDA waiver
2. Contraindications
   1. Use caution and liver function monitoring in hepatitis
3. Mechanism
   1. Partial mu-Opioid receptor agonist
   2. Mu-receptor activation increases with dose to ceiling
      1. No further activation once max dose effect is reached
      2. Hence, unlike heroin or Methadone, low risk of abuse
   3. Slowly dissociates from mu-receptors
      1. May block other Narcotic binding
      2. May displace recently taken Opioids
         1. May result in Opioid Withdrawal symptoms
4. Pharmacokinetics
   1. Metabolism: Liver via P450
   2. Plasma half-life: 37 hours
   3. Routes
      1. Oral bioavailability is too low to be useful
      2. Intravenous route used for pain management
      3. Sublingual is preferred route
         1. Bioavailability: Up to 50% of IV dose
         2. Peak concentration reached 1 hour post-dose
5. Drug Interactions
   1. P450 Inducers may decrease Buprenorphine effect
      1. Carbamazepine
      2. Phenytoin
      3. Phenobarbital
      4. Reverse Transcriptase Inhibitors
      5. Rifampin
   2. P450 Inhibitors may increase Buprenorphine effect
      1. Azole Antifungals (e.g. Ketoconazole, Fluconazole)
      2. Macrolides (e.g. Erythromycin, Azithromycin)
6. Efficacy: Buprenorphine compared with Methadone
   1. Low dose Methadone (<40 mg): Buprenorphine as effective
   2. High dose Methadone (>60 mg): Not as effective
   3. References
      1. Barnett (2001) Addiction 96:683-90
7. Pregnancy
   1. FDA Category C
8. Adverse Effects
   1. Constipation
   2. Urinary Retention
   3. Sedation
   4. Mild respiratory depression
   5. Opioid Withdrawal
9. Toxicity
   1. Overdose has occured when taken with Benzodiazepines
10. Formulations
    1. Pain management
       1. Buprenorphine intravenous
    2. Opioid Addiction
       1. Buprenorphine sublingual
       2. Buprenorphine with Naloxone sublingual
11. Dosing: Prescriber must have FDA waiver
    1. Induction Phase (3-7 days)
       1. Started >12 hours after last short acting Narcotic
       2. Started >24 hours after last long acting Narcotic
       3. Adjusted based on physician evaluation, withdrawal
          1. Day 1: 2 mg every 1-2 hours to max 8-12 mg/day
          2. By day 7: Maximum of 32 mg/day
    2. Stabilization Phase (1-2 months)
       1. Identify minimum effective dose
       2. Typical: Buprenorphine 12-24 mg/day divided
    3. Maintenance Phase (indefinite)
       1. Dosing based on stabilization phase
12. References
    1. Donaher (2006) Am Fam Physician 73(9):1573-8
    2. Fudala (2003) N Engl J Med 349:949-58