CLOZITOR

What it is

CLOZITOR is a clozapine tablet available in strengths of 25 mg, 50 mg, 100 mg, and 200 mg.

Approved indications

— Treatment of people with treatment-resistant schizophrenia, defined as people with schizophrenia who are non-responsive to, or intolerant of other antipsychotic drugs.

Dosing overview

The dosage must be adjusted individually, with the lowest effective dose used for each patient. Initial therapy begins with 12.5 mg once or twice daily on the first day, followed by one or two doses of 25 mg on the second day, then increased slowly in increments of 25 to 50 mg to achieve a dose level of up to 300 mg per day within two to three weeks. In most patients, antipsychotic efficacy can be expected with 200 to 450 mg per day in divided doses. The recommended maximum dose for most patients is 600 mg per day, though a few patients may require up to 900 mg per day in judicious increments not exceeding 100 mg. After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses, with careful downward titration recommended to 150 to 300 mg per day in divided doses.

Key safety warnings

Severe gastrointestinal adverse reactions have occurred with the use of clozapine, resulting in potential outcomes of hospitalisation, surgery and death. Severe gastrointestinal adverse reactions are primarily due to clozapine's potent anticholinergic effects and resulting gastrointestinal hypomotility, with reported effects ranging from nausea, vomiting, overflow diarrhoea, and constipation to paralytic ileus, intestinal impaction, faecal impaction, megacolon, intestinal obstruction, ischaemia, infarction, perforation, ulceration or necrosis, resulting in hospitalisation, surgery and death. Prior to initiating CLOZITOR, screen for constipation and treat as necessary, as early diagnosis and treatment of constipation at the start of clozapine therapy is important in preventing serious gastrointestinal-related complications. Clozapine can cause agranulocytosis and neutropenia, with severe neutropenia (absolute neutrophil count less than 0.5×10⁹/L) occurring in a small percentage of patients and associated with an increase in the risk of serious and potentially fatal infections. Risk of neutropenia appears greatest during the first 18 weeks of treatment and then declines. Before starting clozapine treatment, a white blood cell count and differential count must be performed within ten days prior to starting treatment, then monitored weekly for 18 weeks after the start of treatment, and thereafter performed at least monthly throughout treatment and for one month after complete discontinuation. Cases of myocarditis and cardiomyopathy, some of which have been fatal, and pericarditis have been reported in patients on clozapine. The incidence of myocarditis reported globally is rare (less than 0.1%) during the first month of treatment and very rare (less than 0.01%) thereafter, though the reported incidence in Australia is slightly higher, rated as uncommon (≥0.1% and <1%). Most reported cases of myocarditis have occurred in the first month of treatment, and patients commencing clozapine treatment require close medical supervision. Tachycardia, bradycardia and postural hypotension with or without syncope may occur especially in the initial weeks of treatment, and rarely (about one case per 3,000 patients), collapse can be profound and accompanied by respiratory and/or cardiac arrest, which can be fatal.

Contraindications

CLOZITOR is contraindicated in patients with a history of drug-induced granulocytopenia or agranulocytosis, bone marrow disorders, inability to undergo regular blood tests, circulatory collapse and/or CNS depression due to any cause, alcoholic and other toxic psychoses, drug intoxication, comatose conditions, severe renal or cardiac disease including myocarditis, severe hepatic disease including active hepatic disease associated with nausea, anorexia or jaundice, progressive hepatic disease, hepatic failure, uncontrolled epilepsy, and paralytic ileus. CLOZITOR is also contraindicated in patients who have demonstrated hypersensitivity to clozapine or other components of the product.

PBS listing

No source document contains information about PBS listing for CLOZITOR.

Regulatory history

CLOZITOR clozapine tablets in strengths of 25 mg, 50 mg, 100 mg, and 200 mg were first listed on the ARTG on 17 September 2021.