Opioid 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 per 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: • NVP & EFV: ↓ 50% • LPV/r: ↓ 50% • No clinically significant alterations of methadone PK with other commonly used ART agents	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: ↑ 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, CAB, DOR, DTG, FTR, 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)⁽ⁱⁱ⁾	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

Feature

Methadone

Buprenorphine

Dose required to prevent withdrawal symptoms according to degree of opioid dependency

Linear relationship (from 10-300 mg per 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:
• NVP & EFV: ↓ 50%
• LPV/r: ↓ 50%
• No clinically significant alterations of methadone PK with other commonly used ART agents

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: ↑ 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, CAB, DOR, DTG, FTR, 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)⁽ⁱⁱ⁾

Risk of obstipation

High

Type of administration

Tablet or liquid

Tablet applied sublingual

Risk of further impairment in persons with existing liver impairment

Yes

See Drug-drug Interactions between Analgesics and ARVs
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 ARVs (such as LPV/r, RPV, FTR), amiodarone, astemizole, azithromycin, clarithromycin, chloroquine, citalopram, domperidone, escitalopram, fluconazole and moxifloxacin)