Eli Lilly added strong warnings to the label of Zyprexa, its best-selling medicine for schizophrenia, citing Zyprexa’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 appears to cause high blood sugar more than other medicines for schizophrenia and bipolar disorder, called atypical antipsychotics.
Lilly has previously argued that by those criteria Zyprexa could not be distinguished from its competitors.
The new label will also indicate that patients who take Zyprexa continue to gain weight for as long as two years after starting therapy. That contradicts some 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.
“Today’s communication is part of Lilly’s historical and ongoing commitment to inform doctors and patients about updated prescribing information,” said Dr. Sara Corya, Lilly’s global medical director, in a statement. “Zyprexa is an important treatment option for patients.”
The new warnings may add to the controversy surrounding Zyprexa, which is by far Lilly’s best-selling drug, with 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.
In part because of heavy marketing 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 scant evidence that the new drugs work any better than older generic anti-psychotic medicines 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 Times last December indicated that Lilly was aware of Zyprexa’s tendency to cause weight gain and blood sugar changes by the late 1990’s but played down the drug’s risks because of fears that disclosing them might affect sales. The documents also indicated 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.
Lilly said at the time of those disclosures that the drug’s risks were already reflected in the label.
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, though Lilly says that Zyprexa has never been proven to cause diabetes. 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 steadily for three years, although the revenues it produces for Lilly have not fallen because Lilly has routinely pushed through price increases on the medicine, which can cost $8,000 for a year’s supply of a standard 20-milligram dose.