Drug-Drug Interactions and Individualized Clozapine Therapy in Patients with Depression: Insights from Real-World...

Clozapine is widely used in patients with depression but its metabolism via multiple hepatic enzymes raises concerns about drug-drug interactions (DDIs). The extent of these interactions in real-world clinical settings remains unclear.

This research involved 29 patients with depression from the real world, utilizing their clozapine concentration data, physiological and biochemical data, and drug combination data to construct a DDI evaluation model using the population pharmacokinetics (PPK) method and NONMEM software.

The results of our research reveal that fluvoxamine maleate has a noteworthy DDI with clozapine, and fluvoxamine reduced clozapine clearance by 56.5%, necessitating substantial dose reductions. Furthermore, clozapine doses of 9 mg/kg, 8 mg/kg, 7 mg/kg and 6 mg/kg are recommended for 40-47 kg, 47-70 kg, 70-100 kg and 100-120 kg patients with depression not takingw fluvoxamine maleate, respectively. Clozapine doses of 3 mg/kg and 2 mg/kg are recommended for 40-70 kg and 70-120 kg patients with depression taking fluvoxamine maleate, respectively.

This study provides the first real-world evidence to guide safe and individualized clozapine dosing in patients with depression, particularly in the context of fluvoxamine co-administration. When patients with depression patient are treated with fluvoxamine maleate, the dosage of clozapine needs to be reduced.