Schizophrenia Drug Deaths Inconclusive, FDA Says

Disclosures

March 23, 2015

The US Food and Drug Administration (FDA) announced today that its review of two patients who died after receiving intramuscular injections of the schizophrenia drug olanzapine pamoate (Zyprexa Relprevv, Eli Lilly) is inconclusive, although an animal study appears to exonerate the drug.

As a result, the agency is not recommending any change in how clinicians prescribe olanzapine, or recommending that patients stop using it.

The two patients in question had received appropriate doses of the drug and died three to four days later. The FDA reported their deaths in June 2013. At the time, it wasn't clear whether they had died of postinjection delirium sedation syndrome (PDSS), in which olanzapine enters the bloodstream too fast after an intramuscular injection, causing drug levels to spike. Postmortem levels of olanzapine in the two patients were significantly higher than premortem levels. The FDA tried to answer the question why, and perhaps rule out a PDSS explanation for the deaths.

"We were unable to exclude the possibility that the deaths were caused by rapid, but delayed, entry of the drug into the bloodstream following intramuscular injections," the agency said in a news release today. "The study suggested that much of the drug level increase could have occurred after death."

A study of animals injected with olanzapine showed that bloodstream levels postmortem were as many as seven times higher than those before death, according to the agency. The study, conducted by the manufacturer, also showed that postmortem levels of the drug's metabolite were lower, suggesting that it had converted back to olanzapine, boosting drug levels. In addition, various animal tissues could have served as olanzapine reservoirs that emptied into the bloodstream after death.

The drug's label features a boxed warning for PDSS. Patients must receive an intramuscular injection at a certified facility under an FDA-ordered risk evaluation and mitigation strategy and then undergo observation there for syndrome signs and symptoms for at least three hours.

More information on today's announcement is available on the FDA website.

To report problems with olanzapine, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at https://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.

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