Apo-Quetiapine Drug Interactions

See also Interactions with other medicinal products and other forms of interaction as follows.
Concomitant use of quetiapine with hepatic enzyme inducers such as carbamazepine may substantially decrease systemic exposure to quetiapine. Depending on clinical response, higher doses of quetiapine may need to be considered if quetiapine is used concomitantly with a hepatic enzyme inducer.
During concomitant administration of drugs, which are potent CYP3A4 inhibitors (such as azole antifungals and macrolide antibiotics, and protease inhibitors), plasma concentrations of quetiapine can be significantly higher than observed in patients in clinical trials. (See Pharmacology: Pharmacokinetics under Actions). As a consequence of this, lower doses of quetiapine should be used. Special consideration should be given in elderly and debilitated patients. The risk benefit ratio needs to be considered on an individual basis in all patients.
INTERACTIONS WITH OTHER MEDICAMENTS AND OTHER FORMS OF INTERACTION: Given the primary central nervous system effects of quetiapine, quetiapine should be used with caution in combination with other centrally acting drugs and alcohol.
Caution should be exercised when quetiapine is used concomitantly with drugs known to cause electrolyte imbalance or to increase QT interval (see Precautions).
The pharmacokinetics of lithium was not altered when co-administered with quetiapine.
The pharmacokinetics of valproic acid and quetiapine were not altered to a clinically relevant extent when co-administered as valproate semisodium (also known as divalproex sodium (USAN) and quetiapine (quetiapine fumarate). Valproate semisodium is a stable coordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship.
The pharmacokinetics of quetiapine were not significantly altered following coadministration with the antipsychotics risperidone or haloperidol. However, coadministration of quetiapine and thioridazine caused increases in clearance of quetiapine.
Quetiapine did not induce the hepatic enzyme systems involved in the metabolism of antipyrine. However, in a multiple dose trial in patients to assess the pharmacokinetics of quetiapine given before and during treatment with carbamazepine (a known hepatic enzyme inducer), co-administration of carbamazepine significantly increased the clearance of quetiapine. This increase in clearance reduced systemic quetiapine exposure (as measured by AUC) to an average of 13% of the exposure during administration of quetiapine alone; although a greater effect was seen in some patients. As a consequence of this interaction, lower plasma concentrations can occur, and hence, in each patient, consideration for a higher dose of quetiapine, depending on clinical response, should be considered. It should be noted that the recommended maximum daily dose of quetiapine is 600 to 800 mg/day depending on indication (see Dosage & Administration).
Continued treatment at higher doses should only be considered as a result of careful consideration of the benefit risk assessment for an individual patient. Co- administration of quetiapine with another microsomal enzyme inducer, phenytoin, also caused increases in clearance of quetiapine. Increased doses of quetiapine may be required to maintain control of psychotic symptoms in patients co-administered quetiapine and phenytoin and other hepatic enzyme inducers (eg, barbiturates, rifampicin etc). The dose of quetiapine may need to be reduced if phenytoin or carbamazepine or other hepatic enzyme inducers are withdrawn and replaced with a non-inducer (eg, sodium valproate).
CYP3A4 is the primary enzyme responsible for cytochrome P450 mediated metabolism of quetiapine. The pharmacokinetics of quetiapine was not altered following coadministration with cimetidine, a known P450 enzyme inhibitor. The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antidepressants imipramine (a known CYP2D6 inhibitor) or fluoxetine (a known CYP3A4 and CYP2D6 inhibitor).
In a multiple-dose trial in healthy volunteers to assess the pharmacokinetics of quetiapine given before and during treatment with ketoconazole, co-administration of ketoconazole resulted in an increase in mean C_max and AUC of quetiapine of 235% and 522%, respectively, with a corresponding decrease in mean oral clearance of 84%. The mean half life of quetiapine increased from 2.6 to 6.8 hours, but the mean t_max was unchanged.
Due to the potential for an interaction of a similar magnitude in a clinical setting, the dosage of quetiapine should be reduced during concomitant use of quetiapine and potent CYP3A4 inhibitors (such as azole antifungals, macrolide antibiotics, and protease inhibitors).