Important clinical pharmacologic considerations in the use of methadone in cancer patients

The manufacturer's recommended dose of methadone, which is 2.5-10 mg every 3-4 hours, is excessive. Methadone has an average primary-phase half-life of 14.3 hours and a slower secondary-phase half-life averaging 54.8 hours. Administering the recommended dose of methadone and escalating doses within 2-3 days may lead to very high plasma levels of the drug. In addition, factors such as drug-drug interaction and/or hepatic and renal dysfunction may affect the metabolism of methadone and result in its accumulation. Methadone is an effective analgesic whose pharmacokinetics must be appreciated in order for it to be used safely and effectively. Three cases of methadone overdose are presented.