Drug interactions between Seroquel and thioridazine

MONITOR: Coadministration with thioridazine may decrease the plasma concentrations of quetiapine. The mechanism of interaction is unknown. In one study, thioridazine (200 mg twice a day for 8.5 days) administered to patients stabilized on quetiapine (300 mg twice a day) resulted in decreases in mean quetiapine peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) by 47%, 40% and 31%, respectively. Quetiapine oral clearance (Cl/F) increased by 68%. Patients in the study reported increases in dizziness, insomnia, and dry mouth during coadministration, while sedation and prolonged sleep duration became worse in more than 25% of the patients. This is consistent with additive anticholinergic and CNS-depressant effects of these agents. Excessive anticholinergic effects can also result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Other adverse effects that may be increased with this combination include orthostatic hypotension, extrapyramidal symptoms, and tardive dyskinesia.

MANAGEMENT: Patients treated concomitantly with thioridazine may require a higher dosage of quetiapine to control psychotic symptoms. Pharmacologic response to quetiapine should be monitored more closely whenever thioridazine is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary. Caution is advised when prescribing this combination, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.