Methadone

FDA label

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Titration Pain: increase no more frequently than every 3 to 5 days (steady state not reached before then); some patients require up to 12 days between increases

Renal Undefined

Hepatic Undefined

Peak respiratory depressant effect occurs later and lasts longer than peak analgesic effect; drug accumulates with repeated dosing

Instructions

• Do not abruptly discontinue in physically dependent patients; taper gradually to avoid withdrawal
• Consider prescribing opioid overdose reversal agent (naloxone/nalmefene)
• For addiction, dispense only through certified opioid treatment programs (with limited emergency/inpatient exceptions)
• Avoid overestimating dose when converting from other opioids; underestimate and use rescue medication
• Pain taper (physically dependent patients): reduce by no more than 10-25% of the total daily dose, no more often than every 2 to 4 weeks
• Short-term detoxification: stabilize at about 40 mg/day in divided doses for 2-3 days, then decrease daily or every 2 days keeping withdrawal tolerable (hospitalized patients may tolerate 20%/day reduction)
• Medically supervised withdrawal after maintenance: dose reductions generally less than 10% of the maintenance dose, with 10-14 day intervals between reductions
• Pregnancy: methadone clearance may increase - the dose may need to be increased or the dosing interval decreased
• Acute pain during methadone maintenance: existing methadone dose gives no analgesia; treat with analgesics (incl. opioids), often at somewhat higher/more frequent doses than in non-tolerant patients

Contraindications

• Significant respiratory depression
• Acute or severe bronchial asthma in unmonitored setting or without resuscitative equipment
• Known or suspected GI obstruction, including paralytic ileus

Cautions

• QT prolongation
• MAOIs due to risk of serotonin syndrome
• Adrenal insufficiency
• Severe hypotension; avoid in circulatory shock
• Opioid-induced hyperalgesia
• Risk in chronic pulmonary disease and elderly/cachectic/debilitated patients
• Risk with increased intracranial pressure/head injury

Adverse reactions

• Respiratory depression
• Hypotension
• Lightheadedness, dizziness, sedation
• Nausea, vomiting
• Sweating

Pregnancy No clear increased malformation risk; NOWS expected and treatable after prolonged use in pregnancy

Lactation Present in milk; monitor breastfed infant for drowsiness and breathing difficulties