其 他 安 全 警 示
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| Australia: Clozapine and gastrointestinal hypomotility with severe complications (English only) |
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The Therapeutic Goods Administration (TGA) announces that the potentially fatal risk of gastrointestinal hypomotility in patients taking clozapine has been highlighted with a new boxed warning in the Product Information (PI) for this medicine. Health professionals should assess for constipation before and during treatment with clozapine, and manage suspected constipation promptly to prevent severe complications.
The severe gastrointestinal effects of intestinal obstruction, severe constipation and gastrointestinal hypomotility are among the most serious adverse reactions experienced with clozapine. In post-marketing experience, severe complications of gastrointestinal hypomotility (such as intestinal obstruction, faecal impaction, megacolon, paralytic ileus and intestinal ischaemia or infarction) have resulted in hospitalisation, surgery and death.
The new boxed text and other changes to the PI expand on existing warnings about severe gastrointestinal adverse reactions associated with clozapine, which are primarily due to its potent anticholinergic effects.
The boxed warning states:
Clozapine-induced gastrointestinal hypomotility
Severe gastrointestinal adverse reactions have occurred with the use of clozapine resulting in potential outcomes of hospitalisation, surgery and death (see Section 4.4 Special warnings and precautions for use, and Section 4.8 Adverse effects (undesirable effects)). Prior to initiating and during treatment with clozapine, screen for constipation and, if necessary, manage as per current clinical guidelines.
The changes to the PI note that:
- the subjective symptoms of constipation may not accurately reflect the degree of gastrointestinal hypomotility. Therefore, health professionals should carefully monitor any changes in the frequency or character of a patient’s bowel movements, as well as signs and symptoms of complications of hypomotility, such as:
- nausea and/or vomiting
- abdominal distension and/or pain
- lack of urge and/or inability to defecate
- constipation
- patients with evidence of constipation or gastrointestinal hypomotility should be managed promptly to prevent severe complications
- clozapine should be used with caution and under careful supervision in patients with a current diagnosis or prior history of constipation
- concomitant use of clozapine with anticholinergic medicines should be avoided where possible because of the increased risk of severe gastrointestinal side effects or anticholinergic toxicity.
The PI updates are based on evidence published in the literature and from post-market adverse event data in Australia and internationally. To 1 March 2022, there were 1,523 reports of gastrointestinal disorder for clozapine in the TGA’s Database of Adverse Event Notifications (DAEN), which included 260 reports of constipation, 146 of intestinal obstruction, 93 of abdominal pain and 41 of small intestinal obstruction. Of the 1,023 clozapine reports with a fatal outcome, 103 were due to gastrointestinal disorders.
The adverse reactions listed in the post-marketing experience category in the PI for clozapine are sourced from spontaneous reports and literature, and therefore their frequency is unknown. Megacolon, intestinal infarction/ischaemia, intestinal necrosis, intestinal ulceration and intestinal perforation are listed as potentially fatal adverse gastrointestinal reactions in this category; diarrhoea, abdominal discomfort, heartburn, dyspepsia and colitis are also listed as gastrointestinal adverse reactions, but not as potentially fatal.
Please refer to the following website in TGA for details:
http://www.tga.gov.au/publication-issue/clozapine-and-gastrointestinal-hypomotility-severe-complications
In Hong Kong, there are 9 registered pharmaceutical products containing clozapine. All products are prescription-only medicines. So far, the Department of Health (DH) has received 3 cases of adverse drug reaction related to clozapine, but these cases are not related to gastrointestinal hypomotility. Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 5 Aug 2015, with the latest update posted on 29 Jan 2020. In Dec 2016, the Registration Committee of the Pharmacy and Poisons Board discussed the matter, and decided that the sales pack labels and/or package inserts of clozapine-containing products should include the relevant safety warning. DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/ Saturday, April 23, 2022
Issued at HKT 12:00
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