2004 Safety Alert: Abilify (aripiprazole)

Bristol-Myers Squibb Company

P. O. Box 4500 Princeton, NJ 08543-4500

March 25, 2004

Dear Healthcare Practitioner:

The Food and Drug Administration requested that a warning be added to the prescribing information for all atypical antipsychotics regarding the risk of hyperglycemia and diabetes. This warning advises in part that hyperglycemia, in some cases extreme, has been reported in patients treated with atypical antipsychotics. Attached for your review is the updated full ABILIFY™ (aripiprazole) prescribing information.

The new warning provides information that is specific to ABILIFY, hyperglycemia, and related adverse events:

• "There have been few reports of hyperglycemia inpatients treated with ABILIFY."
• "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..."
• "[E]pidemiological studies which did not include ABILIFY suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics included in these studies."
• "Because ABILIFY was not marketed at the time these studies were performed, it is not known if ABILIFY is associated with this increased risk."

While, as noted above, there have been few reports of hyperglycemia in patients treated with ABILIFY, an exhaustive review of the ABILIFY database revealed no increased signal for diabetes. Additional information is needed to confirm this. However, as noted in the new warning, it is prudent to monitor patients treated with atypical antipsychotics for signs and symptoms of diabetes. Patients with risk factors for diabetes mellitus (e.g., obesity, family history) who are starting treatment with atypical antipsychotics should undergo baseline screening and routine monitoring throughout therapy to mitigate the risk of developing serious metabolic complications.

ABILIFY is indicated for the treatment of schizophrenia. Clinical data demonstrates that ABILIFY delivers proven efficacy with a mean weight change of only 1 kg over 1 year, and is comparable to placebo with respect to lipids.

IMPORTANT SAFETY INFORMATION:

As with all antipsychotic medications, a rare condition referred to as neuroleptic malignant syndrome (NMS) has been reported. As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of tardive dyskinesia (TD).

Abilify (aripiprazole) may be associated with orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.

As with other antipsychotic drugs, Abilify should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Seizures occurred in 0.1 % of patients treated with Abilify in placebo-controlled trials.

Patients should not drive or operate heavy machinery until they are certain Abilify does not affect them adversely.

Treatment-emergent adverse events reported with Abilify at an incidence > I 0% and greater than placebo; respectively, include headache (32% vs 25%), anxiety (25% vs 24%), insomnia (24% vs 19%), nausea (14% vs 10%), vomiting (12% vs 7%), somnolence (11% vs 8%), lightheadedness (11% vs 7%), akathisia (10% vs 7%), and constipation (10% vs 8%).

Please see accompanying full Prescribing Information.

For additional information about ABILIFY, please call 1-800-321-1335 from 9AM to 5PM EST, Monday through Friday.

Sincerely,

Freda Lewis-Hall, MD
Senior Vice President, Medical Affairs
Bristol-Myers Squibb Company

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