The risks of using SEROQUEL XR in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of SEROQUEL XR, caution should be used when it is taken in combination with other centrally acting drugs. Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine.
Because of its potential for inducing hypotension, SEROQUEL XR may enhance the effects of certain antihypertensive agents.
SEROQUEL XR may antagonize the effects of levodopa and dopamine agonists.
The Effect of Other Drugs on Quetiapine
Coadministration of quetiapine (250 mg three times/day) and phenytoin (100 mg three times/day) increased the mean oral clearance of quetiapine by 5-fold. Increased doses of SEROQUEL XR may be required to maintain control of symptoms of schizophrenia in patients receiving quetiapine and phenytoin, or other hepatic enzyme inducers (eg, carbamazepine, barbiturates, rifampin, glucocorticoids). Caution should be taken if phenytoin is withdrawn and replaced with a non-inducer (eg, valproate) [see Dosage and Administration (2)].
Coadministration of quetiapine (150 mg bid) and divalproex (500 mg bid) increased the mean maximum plasma concentration of quetiapine at steady-state by 17% without affecting the extent of absorption or mean oral clearance.
Thioridazine (200 mg bid) increased the oral clearance of quetiapine (300 mg bid) by 65%.
Administration of multiple daily doses of cimetidine (400 mg tid for 4 days) resulted in a 20% decrease in the mean oral clearance of quetiapine (150 mg tid). Dosage adjustment for quetiapine is not required when it is given with cimetidine.
P450 3A Inhibitors
Coadministration of ketoconazole (200 mg once daily for 4 days), a potent inhibitor of cytochrome P450 3A, reduced oral clearance of quetiapine by 84%, resulting in a 335% increase in maximum plasma concentration of quetiapine. Caution (reduced dosage) is indicated when SEROQUEL XR is administered with ketoconazole and other inhibitors of cytochrome P450 3A (eg, itraconazole, fluconazole, erythromycin, protease inhibitors).
Fluoxetine, Imipramine, Haloperidol, and Risperidone
Coadministration of fluoxetine (60 mg once daily); imipramine (75 mg bid), haloperidol (7.5 mg bid), or risperidone (3 mg bid) with quetiapine (300 mg bid) did not alter the steady-state pharmacokinetics of quetiapine.
Effect of Quetiapine on Other Drugs
The mean oral clearance of lorazepam (2 mg, single dose) was reduced by 20% in the presence of quetiapine administered as 250 mg tid dosing.
The mean maximum concentration and extent of absorption of total and free valproic acid at steady-state were decreased by 10 to 12% when divalproex (500 mg bid) was administered with quetiapine (150 mg bid). The mean oral clearance of total valproic acid (administered as divalproex 500 mg bid) was increased by 11% in the presence of quetiapine (150 mg bid). The changes were not significant.
Concomitant administration of quetiapine (250 mg tid) with lithium had no effect on any of the steady-state pharmacokinetic parameters of lithium.
Administration of multiple daily doses up to 750 mg/day (on a tid schedule) of quetiapine to subjects with selected psychotic disorders had no clinically relevant effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites. These results indicate that quetiapine does not significantly induce hepatic enzymes responsible for cytochrome P450 mediated metabolism of antipyrine