FDA investigating Zyprexa Relprevv deaths

FDA is investigating 2 unexplained deaths in patients who received an intramuscular injection of the antipsychotic drug Zyprexa Relprevv (olanzapine pamoate), according to an FDA Drug Safety Communication.

The patients died 3 to 4 days after receiving an appropriate dose of the drug, well after the 3-hour post-injection monitoring period required under the Zyprexa Relprevv Risk Evaluation and Mitigation Strategy (REMS). Both patients were found to have very high olanzapine blood levels after death. High doses of olanzapine can cause delirium, cardiopulmonary arrest, cardiac arrhythmias, and reduced level of consciousness ranging from sedation to coma.

Under the REMS, patients are required to receive the Zyprexa Relprevv injection at a REMS-certified healthcare facility, to be continuously monitored at the facility for at least 3 hours following an injection, and to be accompanied home from the facility. The Zyprexa Relprevv label contains warnings about the risk of post-injection delirium sedation syndrome (PDSS), a serious condition in which the drug enters the blood too fast following an intramuscular injection, causing greatly elevated blood levels with marked sedation (possibly including coma) and/or delirium.

In the clinical trials supporting the approval of Zyprexa Relprevv, cases of PDSS were observed within 3 hours after administration of Zyprexa Relprevv, but there were no deaths due to PDSS. It is not clear whether the 2 patients died from PDSS.

“Patient health and safety are the top priorities at Lilly [the drug’s manufacturer],” Lilly spokesperson Morry Smulevitz said. “Based on the information available to us, we are unable to conclude whether the 2 deaths were related to administration of Zyprexa Relprevv. However, we are continuing to evaluate this important safety issue and will communicate any clinically significant safety information that affects the product. To date, Lilly is not aware of any confirmed cases of PDSS associated with a fatal outcome reported in either clinical trials or in post-marketing use.”

Smulevitz said the FDA safety alert is exclusively related to Zyprexa Relprevv injection and does not affect any other olanzapine products. “We believe the science behind Zyprexa Relprevv has been well-established, and Lilly remains confident in its favorable benefit-risk profile,” he said. “Nearly 50,000 patients worldwide have received olanzapine pamoate in company-sponsored clinical trials and since product approvals.”

FDA advised that if therapy with Zyprexa Relprevv is started or continued in patients, healthcare professionals should follow the REMS requirements and drug label recommendations. Patients and caregivers should talk to their healthcare professional(s) about any questions or concerns.