Quetiapineinteractions

Concomitant use of strong CYP3A4 inhibitors: Reduce quetiapine dose to one sixth when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)

Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. John’s wort)

Discontinuation of strong CYP3A4 inducers: Reduce quetiapine dose by 5 fold within 7-14 days of discontinuation of CYP3A4 inducers

7.1 Effect of

Other Drugs on quetiapine The risks of using quetiapine in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of quetiapine, caution should be used when it is taken in combination with other centrally acting drugs. Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine. Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.) and decreased by the prototype CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.). Dose adjustment of quetiapine will be necessary if it is co-administered with potent CYP3A4 inducers or inhibitors.

CYP3A4 inhibitors: Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure. The dose of quetiapine should be reduced to one sixth of the original dose if co-administered with a strong CYP3A4 inhibitor.

CYP3A4 inducers: Coadministration of quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of quetiapine by 5- fold. Increased doses of quetiapine up to 5 fold may be required to maintain control of symptoms of schizophrenia in patients receiving quetiapine and phenytoin, or other known potent CYP3A4 inducers. When the CYP3A4 inducer is discontinued, the dose of quetiapine should be reduced to the original level within 7-14 days. The potential effects of several concomitant medications on quetiapine pharmacokinetics were studied.

7.2 Effect of

Quetiapine on Other Drugs Because of its potential for inducing hypotension, Quetiapine may enhance the effects of certain antihypertensive agents. Quetiapine may antagonize the effects of levodopa and dopamine agonists. There are no clinically relevant pharmacokinetic interactions of quetiapine on other drugs based on the CYP pathway. Quetiapine and its metabolites are non-inhibitors of major metabolizing CYP’s (1A2, 2C9, 2C19, 2D6 and 3A4).