Because the CYP3A4 isoenzyme plays a major role in the metabolism of methadone, drugs that inhibit CYP3A4 activity may cause decreased clearance of methadone which could lead to an increase in methadone plasma concentrations and result in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of CYP 2C9 and 3A4 inhibitors. If co-administration with methadone hydrochloride tablets is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved [see Clinical Pharmacology () ] .
Methadone is a long acting pain reliever producing effects that last from twelve to forth-eight hours. Ideally, Methadone frees the client from the pressures of obtaining illegal heroin, from the dangers of injection and from the emotional roller coaster that most opiates produce. Methadone, if taken for long periods and at large doses, can lead to a very long withdrawal period. The withdrawals from Methadone are more prolonged and troublesome than those provoked by heroin cessation, yet the substitution and phased removal of methadone is an acceptable method of detoxification for patients and therapists.