Table 1.

Clozapine dose adjustment in patients taking concomitant medications [62]

Co-medications (selected examples)	Scenarios
	Initiating clozapine while taking a co-medication	Adding a co-medication while taking clozapine	Discontinuing a co-medication while continuing clozapine
Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, enoxacin)	Use one-third of the clozapine dose		Increase clozapine dose based on clinical response
Moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, caffeine)	Monitor for adverse reactions. Consider reducing the clozapine dose if necessary		Monitor for lack of effectiveness. Consider increasing clozapine dose if necessary
CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, sertraline)
Strong CYP3A4 Inducers (e.g., phenytoin, carbamazepine, St. John’s wort, rifampin)	Concomitant use is not recommended. However, if the inducer is necessary, it may be necessary to increase the clozapine dose. Monitor for decreased effectiveness		Reduce clozapine dose based on clinical response.
Moderate or weak CYP1A2 or CYP3A4 inducers (e.g., tobacco smoking, omeprazole, dexamethasone, famotidine)	Monitor for decreased effectiveness. Consider increasing the clozapine dose if necessary		Monitor for adverse reactions. Consider reducing the clozapine dose if necessary

CYP3A4 cytochrome P450 3A4, CYP1A2 cytochrome P450 1A2

This table was reproduced from the FDA document "HIGHLIGHTS OF PRESCRIBING INFORMATION - CLOZARIL®”, copyright HLS Therapeutics (USA), Inc. Any changes made to the table are not endorsed by HLS Therapeutics (USA), Inc. CLOZARIL® is a registered trademark of Novartis Pharmaceuticals Corporation [62]