The risks of using SEROQUEL in combination with other drugs have not been extensively evaluated in
systematic studies. Given the primary CNS effects of SEROQUEL, caution should be used when it is taken in combination
with other centrally acting drugs. SEROQUEL potentiated the cognitive and motor effects of alcohol in a clinical
trial in subjects with selected psychotic disorders, and alcoholic beverages should be avoided while taking
Because of its potential for inducing hypotension, SEROQUEL may enhance the effects of certain
antihypertensive agents. SEROQUEL may antagonize the effects of levodopa and dopamine agonists.
The Effect of Other Drugs on Seroquel
Phenytoin: Coadministration of quetiapine (250 mg tid) and phenytoin (100 mg tid)
increased the mean oral clearance of quetiapine by 5-fold. Increased doses of SEROQUEL may be required to maintain
control of symptoms of schizophrenia in patients receiving quetiapine and phenytoin, or other hepatic enzyme inducers
(e.g., carbamazepine, barbiturates, rifampin, glucocorticoids). Caution should be taken if phenytoin is withdrawn and
replaced with a non-inducer (e.g., valproate).
Divalproex: 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: Thioridazine (200 mg bid) increased the oral clearance of quetiapine (300
mg bid) by 65%.
Cimetidine: 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 P4503A, reduced oral clearance of quetiapine by 84%, resulting in a 335% increase in
maximum plasma concentration of quetiapine. Caution is indicated when SEROQUEL is administered with ketoconazole and
other inhibitors of cytochrome P450 3A (e.g., itraconazole, fluconazole, and erythromycin).
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 Seroquel on Other Drugs
Lorazepam: 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.
Divalproex: 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
Lithium: Concomitant administration of quetiapine (250 mg tid) with lithium had no
effect on any of the steady-state pharmacokinetic parameters of lithium.
Antipyrine: 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.