Plain language summary

Methadone is a long-acting medication used to treat opioid dependence. It is usually taken as a liquid at a pharmacy each day as part of a supervised prescribing program. In some situations, such as overseas travel, it may be given as a tablet. This card is a prescribing reference for doctors.

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Medication Reference Card — Opioid Use Disorder

Methadone

Oral liquid · S100 (MATOD) · Standard OTP form · Physeptone® tablets (S8) in specific circumstances only

Dr Basanth Kenchaiah
FRANZCP · MBBS · DPM · DNB (Psychiatry) · Cert. Addiction Psych. Addiction Psychiatrist v1.0 · May 2026
Audience Clinicians
Purpose Prescribing reference for methadone in opioid use disorder — oral liquid (S100, standard OTP form) and tablets (S8, specific circumstances per Victorian MATOD policy).
Key messages
  • Full mu-opioid agonist; oral liquid is the standard OTP form (S100/MATOD); Physeptone® tablets (S8) reserved for specific circumstances only
  • Induction: 10–30 mg Day 1; titrate 5–10 mg every 3–5 days only — accumulation causes delayed toxicity; mandatory clinical review within 24–48 hrs
  • QTc prolongation risk; significant drug interaction burden (CYP3A4/2D6); no ceiling effect for respiratory depression

For Patients

Methadone is a long-acting opioid medication used to reduce cravings and withdrawal from opioid dependence. In Australia, it is most commonly given as a liquid taken daily under supervision at a pharmacy, as part of a structured prescribing program. In some situations — for example, if you are travelling overseas — methadone may be prescribed as a tablet instead of a liquid. Your doctor will explain which form applies to your situation and how your prescription will be managed.

When to prefer methadone over buprenorphine:
Previous buprenorphine treatment failure or poor response High opioid tolerance (IV heroin use, fentanyl) Severe OUD requiring full agonist coverage Chronic pain comorbidity (analgesic benefit) Daily pharmacy attendance feasible and appropriate Patient preference after informed discussion of both options

For Clinicians

Mechanism

Methadone is a full mu-opioid agonist with high oral bioavailability (80–95%), very long and variable half-life (24–36 hrs, up to 120 hrs in some patients), and NMDA receptor antagonism. It accumulates significantly — dose titration must be slow to avoid inadvertent overdose. Unlike buprenorphine, there is no ceiling effect for respiratory depression.

Dosing — Oral Liquid (S100 · Standard OTP Form)

Before initiation: Confirm MATOD enrolment in Victoria. SafeScript check is mandatory before prescribing. Establish dispensing pharmacy and supervised consumption arrangements before the first dose is given.

Induction — Day 1: Assess opioid tolerance carefully. Start 10–30 mg orally (use 10–20 mg if tolerance is uncertain, mixed opioid use pattern, or any concern about over-sedation risk). Do not re-dose on Day 1 — methadone accumulates and delayed toxicity typically occurs 24–72 hrs after initiation. Clinical review within 24–48 hrs is mandatory. Unlike buprenorphine, no COWS threshold is required before initiation — methadone is a full agonist and does not precipitate withdrawal.

Titration: Increase by 5–10 mg no more frequently than every 3–5 days. This interval is not negotiable. The long, variable half-life means each dose increase has a delayed peak effect — increases made more frequently cause inadvertent accumulation and fatal toxicity. Reassess at each titration step.

Maintenance: Typically 60–120 mg/day. Adequate dosing (>60 mg/day) is strongly associated with improved retention in treatment and suppression of illicit opioid use. Under-dosing is a common and avoidable cause of treatment failure — dose should reflect clinical response, not an arbitrary ceiling.

Supervised dispensing: Initially daily supervised consumption at the dispensing pharmacy. Takeaway doses are introduced progressively as clinical stability is demonstrated — frequency and number of takeaways require prescriber endorsement and are subject to MATOD program criteria. SafeScript monitoring applies throughout treatment.


Dosing — Physeptone® Tablets (S8 · Specific Circumstances Only)

Physeptone® 5 mg tablets: scored, divisible. Prescribed under S8 Authority — not S100. Use is restricted to circumstances permitted under the Victorian MATOD policy (see below). Conversion from liquid: 1:1 mg-for-mg — bioequivalent pharmacokinetics; no dose adjustment required when switching a stable patient.

Victorian policy (Dept of Health; effective 1 July 2023, updated 1 July 2024): Methadone is routinely supplied as an oral liquid. Tablets may be considered in one explicitly permitted circumstance:

"In some circumstances, prescribers may consider prescribing methadone take-away doses in the tablet form as an option to enable a stable patient to travel overseas. The decision to prescribe and dispense methadone take-away doses in the tablet form is a matter of professional judgment for the prescriber and pharmacist."

Required documentation: discuss appropriateness with the patient; document clinical reasons for tablet use; assess risks of injection misuse, overdose, and diversion before prescribing.

Outside the MATOD supervised pharmacotherapy programme (e.g. prescription opioid analgesic dependence not enrolled in MATOD), use of methadone tablets is a matter of clinical and professional judgement — document reasoning clearly.

Evidence

The evidence base for methadone treatment is derived from oral liquid formulation studies. Dole & Nyswander (1965) — foundational evidence for methadone OTP. Mattick RP et al. Cochrane Database Syst Rev 2014: methadone significantly superior to placebo for retention and heroin abstinence. No RCTs compare tablet to liquid formulation in OUD — tablets are bioequivalent (equivalent Cmax, AUC, half-life). Tablet-specific risks documented in literature include higher diversion rates and injection misuse risk relative to supervised liquid dispensing.

Cautions
  • QTc prolongation — dose-dependent; baseline ECG required, repeat at 30–40 mg/day and 100+ mg/day; avoid concurrent QTc-prolonging drugs
  • Accumulation risk — long, variable half-life causes delayed toxicity; never increase dose more frequently than every 3–5 days during induction
  • No ceiling effect — unlike buprenorphine, respiratory depression increases linearly with dose; concurrent CNS depressants (benzodiazepines, alcohol, opioids) are particularly dangerous
  • CYP3A4 and CYP2D6 interactions — many common drugs raise or lower methadone levels (fluconazole, rifampicin, carbamazepine, HIV antiretrovirals) — check all interactions before prescribing
  • Concurrent benzodiazepines or alcohol: compound respiratory depression — assess risk vs benefit carefully; dose reduction may be required
  • Tablets — diversion risk higher than liquid — tablets can be concealed, shared, or sold; assess carefully and document rationale before prescribing take-away doses in tablet form
  • Tablets — injection misuse risk — tablets can be crushed and injected; this is a key reason Victorian policy requires documented risk assessment before tablet prescription
  • SafeScript monitoring required in Victoria for all methadone prescribing
  • S8 Authority required (tablets); S100 MATOD enrolment required (oral liquid) — notify relevant state/territory health authority as required
  • Document capacity, consent, clinical rationale, and risk assessment — medico-legal requirement for tablet prescription