FDA Probes Deaths of Two People Taking Lilly Antipsychotic Drug

Federal regulators are investigating two "unexplained" deaths in people who received an injection of an Eli Lilly & Co. antipsychotic drug.

The Food and Drug Administration posted a drug-safety communication on its website Tuesday, saying the patients received an injection of Zyprexa Relprevv and died three to four days afterward. The agency said both patients were found to have "very high" blood levels of the drug in their systems after death. The agency also said both patients had received an appropriate dose of the product.

"Based on the information available to us, we are unable to conclude whether the two deaths were related to administration of Zyprexa Relprevv," Eli Lilly said. "However, we are continuing to evaluate this important safety issue and will communicate any clinically significant safety information that affects the product."

Neither the company nor the FDA would say when the patient deaths occurred, though an FDA spokeswoman said one death was in the U.S. and the other in Europe.

The drug is sold with the brand name Zypadhera outside the U.S. The product had less than $60 million worth of sales in 2012. The oral form of Zyprexa, which is also sold by other drug makers in generic versions, has a wider approval and is also used to treat bipolar disorder and depression that doesn't respond to other treatments.

An Eli Lilly spokesman said the FDA alert involved Zyprexa Relprevv, the long-acting injection, rather than the oral form of Zyprexa. About 50,000 patients world-wide have received the injections.

Zyprexa Relprevv was approved by the FDA in December 2009, after a delay, to treat schizophrenia. In 2008 the agency asked the company for more information about "excessive sedation" that was seen in some patients during clinical trials.

Patients receiving Zyprexa injections are required to be monitored for three hours after receiving the injection. The drug's label contains a warning about the risk of post-injection delirium sedation syndrome, a serious condition in which the drug enters the blood too fast.

The FDA said the condition was seen in clinical trials of Zyprexa Relprevv but no deaths were seen. The FDA said it isn't clear if the two patients died from post-injection delirium sedation syndrome.

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FDA probes deaths linked to Long-Acting Zyprexa

Two patients died 3-4 days after injections with the long-acting antipsychotic drug olanzapine pamoate (Zyprexa Relprevv), prompting an FDA investigation.

The agency has not determined whether the drug caused the fatalities. "At this time, FDA is continuing to evaluate these deaths and will provide an update when more information is available," it said in a statement Tuesday.

Both patients received intramuscular injections of the drug at appropriate doses, the FDA said, but tests showed "very high olanzapine blood levels after death."

High doses are known to induce delirium, cardiopulmonary arrest, cardiac arrhythmias, and impaired consciousness ranging from sedation to coma.

The long-acting form of olanzapine was approved with a risk evaluation and mitigation strategy that requires patients to remain in the clinic for a 3-hour monitoring period and to be escorted home afterward. The requirement was imposed after some patients in clinical trials became delirious or lost consciousness shortly after receiving injections.

These events, dubbed post-injection delirium-sedation syndrome (PDSS), were traced to an unexpectedly rapid release of olanzapine into circulation leading to very high blood levels of the drug.

However, all those cases occurred within hours of injection, not days, and no deaths were attributed to the syndrome, the FDA said.

Olanzapine pamoate is approved for injection every 2-4 weeks for treating patients with schizophrenia. It is one of several long-acting formulations of "atypical" antipsychotic drugs currently available. PDSS has not been seen with those other products.

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