Drug Interactions between clomipramine and methadone

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Concomitant use of methadone with other central nervous system (CNS) depressants (e.g., sedatives/hypnotics, anxiolytics, muscle relaxants, antipsychotics, or tricyclic antidepressants) may result in profound sedation, respiratory depression, coma, and death. In addition, concomitant use of methadone with agents that possess or enhance serotonergic activity may potentiate the risk of a potentially life-threatening condition called serotonin syndrome. The exact mechanism by which serotonin syndrome occurs may differ based on the agent(s) involved. It is thought to result from the hyperstimulation of postsynaptic 5-HT receptors and while postsynaptic 5-HT1A and 5-HT2A receptors are usually implicated, it is more likely that no single receptor is solely responsible. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MONITOR CLOSELY: Methadone can cause dose-related prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. High dosages of methadone alone have been associated with QT interval prolongation and torsade de pointes. In a retrospective study of 17 methadone-treated patients who developed torsade de pointes, the mean daily dose was approximately 400 mg (range 65 to 1000 mg) and the mean corrected QT (QTc) interval on presentation was 615 msec. The daily methadone dose correlated positively with the QTc interval. Fourteen patients had at least one predisposing risk factor for arrhythmia (hypokalemia; hypomagnesemia; concomitant use of a medication known to prolong the QT interval or inhibit the metabolism of methadone; and structural heart disease), but these were not predictive of QTc interval. It is not known whether any of the patients had congenital long QT syndrome.

MANAGEMENT: The use of methadone with other agents that are CNS depressants and/or prolong the QT interval and/or possess or enhance serotonergic activity should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for and counseled about the signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor) as well as prolonged QT interval (irregular heartbeat, dizziness, lightheadedness, fainting) and respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.