Clozapine Safety Advisory

The Therapeutic Goods Administration (TGA) has released a safety advisory regarding clozapine and the potential for severe gastrointestinal side effects. Additional warnings have been added to the product information (PI) and consumer medicine information (CMI) that expand on previous advice concerning this issue.

Clozapine is an antipsychotic indicated for the management of treatment-resistant schizophrenia. It is considered a potent anticholinergic agent, which is thought to be largely responsible for its gastrointestinal adverse effects.

Clozapine-induced gastrointestinal hypomotility can lead to severe complications such as intestinal obstruction, faecal impaction, megacolon, paralytic ileus, and intestinal ischaemia or infarction. The degree of gastrointestinal hypomotility does not always correspond with subjective symptoms of constipation. Therefore, patients should be advised to seek immediate medical advice if they develop constipation or any other signs of reduced gastrointestinal motility. This includes reduced frequency of bowel movements; difficulty passing stool; nausea or vomiting; stomach pains or spasms; or abdominal bloating, tenderness or swelling.

To minimise patient risk, the TGA recommends healthcare professionals:

• Carefully monitor clozapine patients for gastrointestinal effects;
• Promptly manage patients who present with evidence of constipation or gastrointestinal hypomotility;
• Use clozapine with caution in patients with constipation or a history of constipation; and
• Avoid concomitant use of clozapine with other anticholinergic medications.