Coadministration of quetiapine (150 mg twice daily) and divalproex (500 mg twice daily) 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 twice daily) increased the oral clearance of quetiapine (300 mg twice daily) by 65%.

Cimetidine

Administration of multiple daily doses of cimetidine (400 mg three times daily for 4 days) resulted in a 20% decrease in the mean oral clearance of quetiapine (150 mg three times daily). 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 twice daily), haloperidol (7.5 mg twice daily), or risperidone (3 mg twice daily) with quetiapine (300 mg twice daily) did not alter the steady-state pharmacokinetics of quetiapine.

7.2 Effect of Quetiapine 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 three times daily 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 twice daily) was administered with quetiapine (150 mg twice daily). The mean oral clearance of total valproic acid (administered as divalproex 500 mg twice daily) was increased by 11% in the presence of quetiapine (150 mg twice daily). The changes were not significant.

Lithium

Concomitant administration of quetiapine (250 mg three times daily) 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 three times daily 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
Pregnancy Category C:

There are no adequate and well-controlled studies of SEROQUEL XR use in pregnant women. In limited published literature, there were no major malformations associated with quetiapine exposure during pregnancy. In animal studies, embryo-fetal toxicity occurred. Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are limited published data on the use of quetiapine for treatment of schizophrenia and other psychiatric disorders during pregnancy. In a prospective observational study, 21 women exposed to quetiapine and other psychoactive medications during pregnancy delivered infants with no major malformations.