Clozapina

Clozapina, known in English as clozapine, is an atypical antipsychotic medication primarily used for treatment-resistant schizophrenia and for reducing suicide risk in people with schizophrenia. It is prescribed after failure of at least two other antipsychotics and is considered a last-line option because of its safety monitoring requirements and potential adverse effects.

Clozapine has a distinctive receptor profile, with relatively weak D2 antagonism and strong antagonism of 5-HT2A receptors, along with activity at several other receptor systems. This pharmacology may contribute to efficacy on both positive and negative symptoms while reducing extrapyramidal side effects compared with many other antipsychotics. It is mainly metabolized in the liver by cytochrome P450 enzymes, especially CYP1A2, and has an active metabolite called norclozapine.

Safety and monitoring are central to clozapine use. It carries a risk of agranulocytosis, requiring regular blood monitoring. Patients typically enroll in a monitoring program and undergo baseline CBC with ANC, then weekly ANC for the first six months, biweekly for the next six months, and monthly thereafter, depending on local guidelines. Other common adverse effects include weight gain, metabolic changes, sedation, excess salivation, and constipation; rare but serious risks include myocarditis or cardiomyopathy, especially early in treatment, and seizures at higher doses. Clinicians monitor for these risks and adjust treatment accordingly.

Dosing starts at about 12.5–25 mg daily with gradual titration toward a typical target of 300–450 mg/day in divided doses; some patients require higher doses. Smoking can reduce clozapine levels (via CYP1A2 induction), while cessation may increase levels. Interactions with strong 1A2 inhibitors or inducers can markedly alter exposure, necessitating dose adjustments. Clozapina is marketed under several brand names and available in generic form in many regions.