The short-term use of clozapine, a drug
treatment for schizophrenia, has been linked to 12 cases of venous
thromboembolism (blood clot formation in the veins). Five of the cases proved
fatal, researchers report.
"This potentially fatal effect seems to occur mainly in the first 3 months
of clozapine treatment," according to Dr. Staffan Hagg from Norrland University
Hospital in Umea, Sweden, and associates.
The authors examined every case of venous thromboembolism that occurred
during clozapine treatment in Sweden between April 1, 1989 and March 1, 2000.
Their brief report is published in the April 1st issue of The Lancet.
Six of the 12 cases included pulmonary embolism (blood clots in the lungs),
and six cases included blood clots in the deep veins of the legs, the results
indicate. Two thirds of the cases occurred during the first 3 months of
clozapine treatment.
Only one of the patients had a known risk factor for venous thromboembolism
(she took oral contraceptives), the investigators note, although complete
information on all risk factors was not available for all patients.
Whereas only 61% of the clozapine prescriptions were for men, the
researchers observe, 77% of the venous thromboembolism patients were men. "Men
might, therefore, be more prone to develop this reaction," they write.
Based on the estimated exposure of 20,000 to 70,000 Swedish patients to
clozapine, the investigators suggest that "the assumed risk of venous
thromboembolism would, therefore, be at least 1 per 2000 - 6000 treated
patients."
"Venous thromboembolism might be associated with use of clozapine," the
authors conclude. "Clozapine should be stopped in any patient in whom this
reaction is suspected," they add.
"Although thromboembolism is a possible side effect of clozapine and similar
therapies, the insufficient population data in this article make it difficult to
determine whether the incidence reported here is greater than that of the
general population," Harry Rohme, Communications Coordinator for Clozaril at
Novartis Pharmaceuticals Corporation (clozapine's manufacturer) in East Hanover,
New Jersey, told Reuters Health.
"Furthermore," Rohme noted, "the clozapine patient population is inherently
a high-risk group and many have risk factors associated with thromboembolic
events, including a history of heavy smoking, obesity, and polypharmacy
(concurrent use of many medications)."
"While it is not clear whether the cases... can be attributed to clozapine
therapy, Novartis takes all reports regarding patient safety very seriously and
is investigating the matter thoroughly," Rohme concluded.
