Clozaril is an Atypical Antipsychotic drug used to treat schizophrenia. Clozaril (Generic: Clozapine) was approved by the FDA on April 28, 1997 is manufactured by Novartis Pharmaceuticals. Clozaril has been linked with diabetes, hyperglycemia and pancreatitis. These findings, from researchers at Duke University and the Food and Drug Administration appear in the January 2005 issue of the Journal of the American Medical Association (JAMA).
The Journal of Clinical Psychiatry reported that the FDA was made aware of more than 140 cases of new-onset diabetes in patients taking Clozaril. Three dozen cases involved ketoacidosis, a potentially deadly complication of elevated blood sugar. The paper also cited 19 case reports of diabetes associated with the use of Olanzapine, sold as Zyprexa by Indianapolis-based Eli Lilly and Co.
In the new research, Dr. Elizabeth Koller, an FDA medical officer, and colleagues culled the agency’s MedWatch database for blood sugar trouble associated with Clozaril and Zyprexa. 11 reports of runaway blood sugar in patient’s ages 13 to 18 taking Clozaril between January 1993 and March 2004 were found. Additionally nine reports of similar complications among teens taking Zyprexa between January 1996 and May 2001 were discovered.
Of the patient’s on Zyprexa, seven had new diagnosis of hyperglycemia. The sugar disorder developed within a week of taking Zyprexa in two patients and within six months for eight others. One patient ultimately died of necrotizing pancreatitis, a condition in which cells in the pancreas die.
One youth taking Clozaril also developed pancreatitis more than a month after stopping the drug. That patient survived. Available information showed that eight of the clozapine patients with high blood sugar never had the problem before. Although the patients on Olanzapine also were taking a wide range of other medications, those on Clozarile took only one other medication. Researchers estimate the rate of hyperglycemia among young clozapine users is 10 times greater than among the general population.
The million-dollar question is whether the cases in the MedWatch database are the tip of the iceberg or not. We don’t have a good sense for what percent of serious adverse events that occur in practice with marketed drugs are ever reported to the FDA, co-author P. Murali Doraiswamy, a Duke University psychiatrist, says in a statement.
The connection between pancreatitis and these drugs is not fully known
The connection between pancreatitis and these drugs is not fully known, but given its background
rate is so rare, I suspect it’s a drug toxicity,Doraiswamy says in an e-mail interview.
Tawny Bettinger, a brain drug expert at the University of Texas Southwestern Medical Center who has studied the effects of antipsychotics on blood sugar, says the problem is gaining attention among mental health experts. They don’t know the causes of it, or why it’s happening,says Bettinger, who cites a number of case studies, including one she published, that have appeared in the last several years.
In her own work, Bettinger and her colleagues saw that a diabetic woman taking olanzapine quickly developed runaway blood sugar that previously had been under control with a careful diet. Once the woman started on the drug, even insulin and other sugar-quelling medications couldn’t keep her glucose in check.
Clozapine’s better-understood side effect is a potentially grave falloff in white blood cells, a problem called agranulocytosis that the FDA has recognized for some time. Patients starting on Clozapine must undergo regular blood tests to watch for the condition.
Additionally, Clozaril was linked to dozens of cases of heart complications, including at least 28 deaths since the late 1980s. Novartis, which makes a brand-name version of the pill, has contested those figures. Even so, many mental health experts consider the compound a miracle drug for patients with otherwise untreatable psychosis.
In the United States, warning labels on atypical antipsychotics list the possibility of sugar problems in patients who use them, but they aren’t highlighted in any special way,Doraiswamy says. In Japan, they have a much stronger warning that is highlighted and appears at the very first beginning of the label. However, Doraiswamy says, “It’s difficult to further change the label in the United States without having a sense for whether this is a unique problem with one or two drugs or applies to the entire class.