The U.S. Food and Drug Administration is investigating the cases of two individuals who died after injections with Eli Lilly and Co.'s long-acting treatment for schizophrenia, Zyprexa Relprevv.
Both patients died three to four days after receiving "an appropriate dose" of the medicine, and both had very high levels of the drug in their bloodstreams, the FDA said in a bulletin released on its website on Tuesday.
The medicine's package insert carries a prominent "black box" warning of risk from post-injection delirium sedation syndrome, or PDSS, a serious condition in which the drug enters the blood too quickly following an injection, causing greatly elevated levels of the drug in the bloodstream. High doses of the drug can cause delirium, cardiopulmonary arrest, heart rhythm problems, sedation and coma, the FDA said.
Lilly said it was not clear whether the two deaths were related to use of the drug.
"We are continuing to evaluate this important safety issue and will communicate any clinically significant safety information that affects the product," Lilly spokesman Morry Smulevitz said in an emailed statement.
About 45,000 people have taken the drug worldwide since the FDA approved it in late 2009.
In Lilly's clinical trials of Zyprexa Relprevv, cases of PDSS were seen within three hours of taking the drug, but no deaths from the syndrome were seen, the FDA said.
Zyprexa Relprevv comes with warnings that patients must stay at the doctor's office for at least three hours after it is given so they can be monitored.
The drug is a long-acting version of Lilly's widely used oral Zyprexa treatment, which was the company's biggest product until it began facing competition from cheaper generics in 2011.
Zyprexa Relprevv competes with other long-acting treatments such as Johnson & Johnson's Invega Sustenna. It is meant to offer weeks of symptom control for schizophrenia patients, who often fail to take their medication regularly.
Lilly's Smulevitz said 82 previous deaths of patients who took the drug had been reported since the drug was introduced, but that Lilly could determine no "pattern, trend or causal connection" between the deaths and use of the drug. Tuesday's FDA safety alert was the first issued by the FDA on the product, he said.
Asked why the agency had highlighted the two most recent deaths, FDA spokeswoman Sandy Walsh said, "These deaths are unique because we have postmortem blood levels (of the drug) that were very high and the cause of death was not clear." She said the FDA's investigation is continuing.
Dr. Dolores Malaspina, professor of psychiatry at New York University School of Medicine, said the unresolved safety issue was of concern, but not likely to decrease demand for Zyprexa Relprevv or similar medicines.
"These drugs are absolutely necessary, but we need to constantly think of the risks and benefits to make sure people with mental illness get adequate medical care, not just psychiatric care," Malaspina said.
She noted that people with schizophrenia and other severe mental illnesses, on average, have life spans many years lower than the general population, especially because of heart disease and metabolic diseases like diabetes.
Lilly said Zyprexa Relprevv's global sales were "less than $60 million" in 2012. The company has annual sales of more than $20 billion.
Global sales of Lilly's Zyprexa franchise plunged 49 percent to $284 million in the first quarter of 2013 as cheaper generic forms of the oral treatment continued to gain market share.
Lilly shares were little changed Tuesday on the New York Stock Exchange.
(Reporting by Ransdell Pierson; Editing by Gerald E. McCormick, Alden Bentley, John Wallace and Dan Grebler)