Drug-Drug Interactions: Given the primary central nervous system effects of quetiapine, quetiapine should be used with caution in combination with other centrally acting drugs.
Caution should be exercised when quetiapine is used concomitantly with drugs known to cause electrolyte imbalance or to increase QT interval (see Cardiovascular: QT Prolongation under Precautions).
Urinary Hesitation and Retention: Caution should be exercised in prescribing pms-QUETIAPINE to patients who are receiving other medications that have anticholinergic (muscarinic) properties and may affect voiding (see Neurologic: Anticholinergic (Muscarinic) Effects under Precautions).
The Effect of Quetiapine Fumarate on Other Drugs: Alcohol: Quetiapine fumarate immediate-release potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with psychotic disorders. Alcoholic beverages should be avoided while taking quetiapine.
Antihypertensive Agents: Because of its potential for inducing hypotension, quetiapine may enhance the effects of certain antihypertensive agents.
Levodopa and Dopamine Agonists: As it exhibits in vitro dopamine antagonism, quetiapine may antagonize the effects of levodopa and dopamine agonists.
Lithium: The single dose pharmacokinetics of lithium were not altered when coadministered with quetiapine fumarate.
Antipyrine: Quetiapine fumarate did not induce the hepatic enzyme systems involved in the metabolism of antipyrine.
Lorazepam: Quetiapine fumarate did not affect the single dose pharmacokinetics of lorazepam.
Divalproex: Co-administration of quetiapine fumarate (150 mg bid) and divalproex (500 mg bid) increased the mean oral clearance and the mean maximum plasma concentration of total valproic acid (administered as divalproex) by 11%. These changes were not clinically relevant.
The Effect of Other Drugs on Quetiapine Fumarate: Hepatic Enzyme Inducers: Concomitant use of quetiapine with hepatic enzyme inducers such as carbamazepine may substantially decrease systemic exposure to quetiapine. 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 pms-QUETIAPINE is 800 mg/day and 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 and another microsomal enzyme inducer, phenytoin, caused five-fold increases in the 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 (e.g., 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 (e.g., sodium valproate).
CYP 3A4 inhibitors: CYP 3A4 is the primary enzyme responsible for cytochrome P450-mediated metabolism of quetiapine. Thus, coadministration of compounds (such as ketoconazole, erythromycin, clarithromycin, diltiazem, verapamil, or nefazodone), which inhibit CYP 3A4, may increase the concentration of quetiapine. 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, but the mean tmax 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 CYP 3A4 inhibitors (such as azole antifungals, macrolide antibiotics, and protease inhibitors). 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.
Divalproex: Co-administration of quetiapine fumarate (150 mg bid) and divalproex (500 mg bid) increased the mean maximum plasma concentration of quetiapine by 17% without changing the mean oral clearance.
Cimetidine: In a clinical study examining the pharmacokinetics of quetiapine fumarate following coadministration with cimetidine, (a non-specific P450 enzyme inhibitor), no clinically significant interaction was observed.
Thioridazine: Coadministration of thioridazine (200 mg b.i.d.) with quetiapine fumarate (300 mg b.i.d.), increased the clearance of quetiapine fumarate by 65%.
Fluoxetine, Imipramine, Haloperidol, and Risperidone: Fluoxetine (60 mg daily), imipramine (75 mg b.i.d.), haloperidol (7.5 mg b.i.d.), and risperidone (3 mg b.i.d.) did not significantly alter the steady state pharmacokinetics of quetiapine.
Drug-Food Interactions: pms-QUETIAPINE can be administered with or without food.
Drug-Herb Interactions: Interactions with herbal products have not been established.
Drug-Laboratory Interactions: There have been reports of false positive results in enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine. Confirmation of questionable immunoassay screening results by an appropriate chromatographic technique is recommended.