Seroquel XR

Seroquel XR Drug Interactions

quetiapine

Manufacturer:

AstraZeneca

Distributor:

DKSH
Full Prescribing Info
Drug Interactions
See also 'Interaction with other medicaments and other forms of interaction' in the following text.
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 Seroquel XR 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, macrolide antibiotics, and protease inhibitors), plasma concentrations of quetiapine can be significantly higher than observed in patients in clinical trials. As a consequence of this, lower doses of Seroquel XR 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.
Interaction with other medicinal products and other forms of interaction: Given the primary central nervous system effects of quetiapine, Seroquel XR 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 Seroquel.
The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered.
The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antipsychotics risperidone or haloperidol. However co-administration of Seroquel and thioridazine caused increases in the 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 Seroquel XR, depending on clinical response, should be considered. The safety of doses above 800 mg/day has not been established in the clinical trials.
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 Seroquel XR with another microsomal enzyme inducer, phenytoin, also caused increases in the clearance of quetiapine. Increased doses of Seroquel XR may be required to maintain control of psychotic symptoms in patients co-administered Seroquel XR and phenytoin, and other hepatic enzyme inducers (e.g., barbiturates, rifampicin etc.). The dose of Seroquel XR may need to be reduced if phenytoin or carbamazepine or other hepatic enzyme inducers are withdrawn and replaced with a non-inducer (e.g., sodium valproate).
CYP3A4 is the primary enzyme responsible for cytochrome P450 mediated metabolism of quetiapine. The pharmacokinetics of quetiapine were not altered following co-administration 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 Cmax 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. Due to the potential for an interaction of a similar magnitude in a clinical setting, the dosage of Seroquel XR should be reduced during concomitant use of quetiapine and potent CYP3A4 inhibitors (such as azole antifungals, macrolide antibiotics, and protease inhibitors).
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in