Drug Interactions between prochlorperazine and propoxyphene

MONITOR CLOSELY: Concomitant use of propoxyphene and phenothiazines may result in additive central nervous system (CNS) depressant effects. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly, and the risk was further increased by concomitant use of psychotropic agents including neuroleptics, presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene may increase the plasma concentrations of phenothiazines by inhibiting their metabolism via CYP450 2D6. In addition to enhanced CNS depression, the possibility of increased adverse effects of phenothiazines such as tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered. Many of these agents alone can and have produced these effects.

MANAGEMENT: Caution is advised if propoxyphene is prescribed with phenothiazines, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Dosage reductions may be required. Patients should be warned not to exceed recommended dosages, to avoid alcohol, and to notify their physician if they experience symptoms of toxicity such as lethargy, excessive sedation, dizziness, syncope, seizures, and/or irregular heartbeat. In addition, they should avoid activities requiring mental alertness until they know how these agents affect them.