Drug Dependency / Addiction

Drug Dependency and Drug Addiction

Characteristics of drugs used as opioid substitution therapy (OST)(i)

Feature Methadone Buprenorphine
Dose required to prevent withdrawal symptoms according to degree of opioid dependency Linear relationship (from 10-300 mg pr day) Linear relationship for persons with less opioid dependency only – ceiling effect (max daily dose 24 mg)
Interaction with ARVs Methadone plasma concentrations are reduced if used together with NNRTIs or PIs:
• NVP & EFV: ↓ 50%
• ETV: ↓ < 10%(ii)
• LPV/r: ↓ 50%
• SQV/r, DRV/r, FPV/r: ↓ 15-25%
• ATV, IDV: ↓ < 10%
Buprenorphine (B) and active metabolite norbuprenorphine (N) plasma concentrations are reduced if combined with NNRTIs and increased if combined with some PIs or INSTIs
• EFV: ↓ up to 50% (B) and 70% (N)
• ETV: ↓ 25% (B)
• ATV/r, IDV, SQV/r: ↑ 50-100% (B&N)
• DRV/r: ↑ 50% (N)
CAVE: B reduces ATV; do not use without RTV or COBI boosting
• EVG/c, ↑ 35-42% (B&N) (BIC, DTG, RAL, RPV & LPV/r do not affect B&N metabolism)
  CAVE: withdrawal symptoms if combined with ARV that decreases plasma concentration and risk of drug toxicity if such ARVs are interrupted – reverse if ARVs increase plasma concentration
Risk of overdose Yes No, if used as a co-formulation with naloxone
Causing QT prolongation on ECG Yes (dose-response relationship)(iii) No
Risk of obstipation High High
Type of administration Tablet or liquid Tablet applied sublingual
Risk of further impairment in persons with existing liver impairment Yes Yes

 

  1. See Drug-drug Interactions between Analgesics and ARVs
  2. Note that despite ETV causes a decrease in the plasma concentration of methadone, the active methadone enantiomer is in fact increased 6% by ETV
  3. ECG recommended for daily methadone doses exceeding 50 mg; special caution with concomitant use of other drugs known to cause QT prolongation (e.g. certain PIs such as SQV/r as well as albuterol (USAN) or salbutamol (INN), amiodarone, amitriptyline, astemizole, chloroquine, clomipramine and moxifloxacin)