The FDA has concluded the review of a study undertaken to determine the cause of elevated levels of the long-acting, injectable schizophrenia drug Zyprexa Relprevv (olanzapine pamoate) in two patients who died. 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.
This review is an update to the FDA Drug Safety Communication issued on June 18, 2013. The study results were inconclusive. The FDA was unable to exclude the possibility that the deaths were caused by rapid, but delayed, entry of the drug into the bloodstream following intramuscular injection. The study suggested that much of the drug level increase could have occurred after death, a finding that could explain the extremely high blood levels found in the two patients who died three to four days after receiving injections of appropriate doses of Zyprexa Relprevv. On the basis of all of the information reviewed, the FDA is not recommending any changes to the current prescribing or use of Zyprexa Relprevv injection at this time. Patients should not stop receiving treatment without first talking to their health care professionals
Treatment with Zyprexa Relprevv may help improve the symptoms of schizophrenia, which include hearing voices, seeing things that are not there, and being suspicious or withdrawn. The labeling for Zyprexa Relprevv carries a boxed warning, the FDA’s most serious type of warning, for post-injection delirium sedation (PDSS). PDSS is a serious condition with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma), delirium, or both. In clinical trials, cases of PDSS were observed within three hours after giving an intramuscular injection of Zyprexa Relprevv, although no deaths were reported. To reduce the risk of PDSS, there is also a Risk Evaluation and Mitigation Strategy (REMS) for Zyprexa Relprevv to ensure that patients are observed by health care professionals at a certified facility following injection.
Following the deaths of the two patients who received appropriate doses of Zyprexa Relprevv, the FDA requested the drug’s manufacturer, Eli Lilly and Company, to conduct an animal study to test whether movement of olanzapine into blood after death could lead to higher-than-expected blood levels of the drug. The study showed that some animals had increases in drug levels in the blood after death, which could account for the higher-than-expected blood levels found in the two patients who died.
Health care professionals should continue to follow the Zyprexa Relprevv Patient Care Program REMS requirements and current label recommendations. Notable requirements of the REMS include:
- For a patient to receive treatment, the prescriber, health care facility, patient, and pharmacy must all be enrolled in the Zyprexa Relprevv Patient Care Program.
- Zyprexa Relprevv injections must be administered at a REMS-certified health care facility with ready access to emergency response services.
- Patients must be continuously monitored at the REMS-certified health care facility for at least three hours following an intramuscular injection.
- Patients receiving Zyprexa Relprevv must be accompanied to their destination from the health care facility.
Patients should read the Medication Guide that comes with the Zyprexa Relprevv prescription each time before they get an intramuscular injection, as there may be new information. Patients receiving Zyprexa Relprevv or their caregivers should immediately report symptoms of PDSS to a health care professional. Symptoms of PDSS can include feeling more sleepy than usual, feeling dizzy, feeling confused or disoriented, having trouble talking or walking, having higher blood pressure or seizures or becoming unconscious.
See the FDA Drug Safety Communication
See also Medical Law Perspectives, May 2013 Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication