Methadone

Renal Impairment Methadone pharmacokinetics have not been extensively evaluated in patients with renal insufficiency. Since unmetabolized methadone and its metabolites are excreted in urine to a variable degree, start these patients on lower doses and with longer dosing intervals and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression.

Hepatic Impairment Methadone pharmacokinetics have not been extensively evaluated in patients with hepatic insufficiency. Methadone is metabolized by hepatic pathways; therefore, patients with liver impairment may be at risk of increased systemic exposure to methadone after multiple dosing. Start these patients on lower doses and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression.

Important Dosage and Administration Information Methadone hydrochloride tablets for oral suspension are for oral administration only. The preparation must not be injected. Methadone should be kept out of reach of children to prevent accidental ingestion . Consider the following important factors that differentiate methadone from other opioids: The peak respiratory depressant effect of methadone occurs later and persists longer than its peak pharmacologic effect.

A high degree of opioid tolerance does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during initiation of methadone treatment of addiction in subjects previously abusing high doses of other opioid agonists.

There is high interpatient variability in absorption, metabolism, and relative analgesic potency. Population-based conversion ratios between methadone and other opioids are not accurate when applied to individuals. With repeated dosing, methadone is retained in the liver and then slowly released, prolonging the duration of potential toxicity.

Steady-state plasma concentrations are not attained until 3 to 5 days after initiation of dosing. Methadone hydrochloride tablets for oral suspension have a narrow therapeutic index, especially when combined with other drugs.