CLOZARIL

What it is

CLOZARIL is available as tablets containing 25 mg, 50 mg, 100 mg or 200 mg of clozapine. A suspension formulation is also available, containing 50 mg of clozapine per 1 mL.

Approved indications

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

Dosing overview

Dosage must be adjusted individually, with the lowest effective dose used for each patient. Treatment starts 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. If well tolerated, the daily dose may then be 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, with the total daily dose often divided unevenly, with the larger portion at bedtime. The recommended maximum dose for most patients is 600 mg per day, although a few patients may require doses up to a maximum of 900 mg per day.

Key safety warnings

Severe gastrointestinal adverse reactions have occurred with clozapine, potentially resulting in hospitalisation, surgery and death. Prior to initiating and during treatment, screening for constipation and management as per current clinical guidelines is necessary. Severe gastrointestinal adverse reactions range from nausea and vomiting to paralytic ileus, intestinal impaction and more severe complications including faecal impaction, megacolon, intestinal obstruction, ischaemia, infarction, perforation and necrosis, which have resulted in hospitalisation, surgery and death. 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, although the reported incidence of myocarditis in Australia is slightly higher, being rated as uncommon (0.1% to less than 1%). Most reported cases of myocarditis have occurred in the first month of treatment, and patients commencing clozapine treatment require close medical supervision. Clozapine can cause agranulocytosis and severe neutropenia, which occurs in a small percentage of patients and is associated with an increased risk of serious and potentially fatal infections. The risk of neutropenia appears greatest during the first 18 weeks of treatment and then declines. After the start of clozapine treatment, white blood cell and absolute neutrophil counts must be monitored weekly for 18 weeks, thereafter at least monthly throughout treatment and for one month after complete discontinuation of clozapine. Tachycardia, bradycardia and postural hypotension with or without syncope may occur especially in the initial weeks of treatment. Rarely (about one case per 3,000 patients), collapse can be profound and accompanied by respiratory and/or cardiac arrest, and these reactions can be fatal.

Contraindications

CLOZARIL is contraindicated in patients with a history of drug-induced granulocytopenia or agranulocytosis; bone marrow disorders; those unable to undergo regular blood tests; circulatory collapse and/or CNS depression due to any cause; and alcoholic and other toxic psychoses, drug intoxication, or comatose conditions. It is also contraindicated in patients with severe renal or cardiac disease (including myocarditis), and severe hepatic disease including active hepatic disease associated with nausea, anorexia or jaundice, progressive hepatic disease, or hepatic failure. Uncontrolled epilepsy and paralytic ileus are also contraindications.

PBS listing

CLOZARIL 25 mg tablets are listed on the PBS with 3 items under streamlined restriction at an ex-manufacturer price of A$27.75. CLOZARIL 100 mg tablets are listed on the PBS with 3 items under streamlined restriction at an ex-manufacturer price of A$104.04.

Regulatory history

CLOZARIL clozapine 25 mg and 100 mg tablets were first registered on the ARTG on 21 November 1994. Additional CLOZARIL ODT (orally disintegrating tablet) formulations in strengths of 12.5 mg, 25 mg, 50 mg, 100 mg and 200 mg were first listed on the ARTG on 30 March 2026.