FDA Warning Regarding Zyprexa

March 1, 2004

Re: Safety data on Zyprexa (r) (olanzapine) - Hyperglycemia and Diabetes

Dear Doctor,

Eli Lilly and Company would like to inform you of important labeling changes regarding Zyprexa (olanzapine). The Food and Drug Administration (FDA) has asked all manufacturers of atypical antipsychotic medications, including Lilly, to add a Warning statement describing the increased risk of hyperglycemia and diabetes in patients taking these medications, including Zyprexa. In addition to Zyprexa, the atypical antipsychotic class includes Clozaril (r) (clozapine, Novartis), Risperdal (r) (risperidone, Janssen), Seroquel (r) (quetiapine, AstraZeneca), Geodon (r) (ziprasidone, Pfizer), and Abilify (r) (aripiprazole, Bristol Myers Squibb and Otsuka American Pharmaceutical). Accordingly, the Zyprexa prescribing information has been updated with the following information:

WARNINGS

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including Zyprexa. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia related adverse events in patients treated with atypical antipsychotics are not available.

Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

Should you have any questions or concerns regarding this important safety information, please contact your Eli Lilly and Company sales representative or contact the Lilly medical department at 1-800-Lilly-Rx . Please refer to the full prescribing information for Zyprexa included with this letter. As always, we request that serious adverse events be reported to Lilly at 1-800-Lilly-Rx or to the FDA MedWatch program by phone (1-800-FDA-1088 ), by fax (1-800-FDA-0178 ) or by email (www.fda.gov/medwatch).

Sincerely,



Dr. Paul Eisenberg
Vice President, Global Product Safety
Eli Lilly and Company