Lilly Adds Strong Warning Label to Zyprexa, a Schizophrenia Drug

By ALEX BERENSON
Eli Lilly yesterday added strong warnings to the label of Zyprexa, its best-selling medicine for schizophrenia, citing the drug’s tendency to cause weight gain, high blood sugar, high cholesterol and other metabolic problems.
For the first time, Zyprexa’s label now acknowledges that the drug causes high blood sugar more than some other medicines for schizophrenia and bipolar disorder, called atypical antipsychotics.
Lilly previously argued that Zyprexa had not been proved to cause high blood sugar at a more frequent rate than its competitors.
Concern about Zyprexa’s side effects has been increasing since at least 2004, and Zyprexa’s prescriptions and market share have fallen sharply over the period. As a result, the new warnings may have only a moderate impact among doctors and patients, said S. Nassir Ghaemi, director of the Bipolar Disorder Research Program at Emory University.
“The knowledge has been out there, and it’s already impacted prescribing patterns a great deal,” Dr. Ghaemi said.
The new label will also indicate that patients who take Zyprexa may keep gaining weight for as long as two years after starting therapy. That contradicts earlier public statements by Lilly that weight gain on Zyprexa tends to plateau after a few months of use. One in six patients who take Zyprexa will gain more than 33 pounds after two years of use, the label says.
Weight gain and high blood sugar are risk factors for diabetes, although Lilly says there has been no proof that Zyprexa causes diabetes more than its competitors do.
“Obviously, we know that weight gain is a known risk factor for diabetes,” said Marni Lemons, a Lilly spokeswoman. “However, not all patients who gain weight develop diabetes.”
Ms. Lemons also noted that older antipsychotic medicines also have severe side effects, including a tendency to cause facial tics.
The new warnings may add to the controversy surrounding Zyprexa, which is by far Lilly’s best-selling drug.
Zyprexa had global sales of more than $2.3 billion in the first half of this year and nearly 3 million prescriptions in the United States alone. Lilly said it had made the label changes as a part of continuing discussions with the Food and Drug Administration.
Lilly has asked the F.D.A. to allow it to begin marketing Zyprexa for adolescents, despite clinical trial data showing that Zyprexa causes weight gain and metabolic problems in teenagers that can be even more severe than in adults.
Heavily marketed by drug companies, atypical antipsychotic medicines have become one of the biggest and fastest-growing drug classes.
Overall sales for the category are projected at close to $13 billion this year, despite little evidence that the new drugs work better than older generics that cost just pennies a pill.
The label changes come 11 years after Lilly began selling Zyprexa and more than 12 years after a large Lilly clinical trial first showed that Zyprexa might have negative effects on weight and blood sugar.
Internal Lilly documents disclosed by The New York Times last December indicated that Lilly was aware of Zyprexa’s tendency to cause weight gain and blood sugar changes by the late 1990s but played down the risks.
Lilly said at the time of those disclosures that the drug’s risks were already reflected in the label. Ms. Lemons said the company had not delayed releasing information about Zyprexa’s side effects, and had made yesterday’s label change after a new review of clinical trials showed the drug’s potential risks.
“It’s not like this is information that we have had since 1995,” Ms. Lemons said.
The documents disclosed by The Times in December also indicated that Lilly had told its sales representatives to encourage doctors to prescribe Zyprexa to people who do not have schizophrenia or bipolar disorder, Zyprexa’s only approved uses.
Federal laws prohibit drug companies from so-called off-label marketing, although doctors may prescribe drugs for whatever use they see fit.
Lilly has spent $1.2 billion since 2004 to settle lawsuits from 28,500 people who claimed they developed diabetes or heart problems after taking the drug. At least 1,200 more lawsuits are still pending.
In 2004, the American Diabetes Association said that Zyprexa was more likely to cause diabetes than other commonly prescribed antipsychotic medicines, although the F.D.A. has never made a distinction between Zyprexa and other drugs.
Even now, Zyprexa’s label does not say it causes diabetes more than the other medicines, only high blood sugar.
In the United States, Zyprexa’s prescriptions and market share have slid for three years. But the revenue it produces for Lilly has not fallen because Lilly has pushed through price increases on the medicine, which can cost $8,000 for a year’s supply of a standard 20-milligram dose.