FDA has approved Zyprexa, injectable anti-psychotic drug

Mar 30 2004

Physicians have a new fast-acting option for controlling the potentially crippling effects of acute agitation in patients suffering with schizophrenia and bipolar mania. The U.S. Food and Drug Administration (FDA) has approved Zyprexa^® IntraMuscular (olanzapine for injection), an injectable form of Lilly's top-selling medication.

Clinical data demonstrate that Zyprexa IntraMuscular enables physicians to rapidly and dependably relieve patients of the effects of acute agitation without many of the debilitating side effects of conventional injectable therapies. This new formulation of Zyprexa is the first medication in its class to be indicated for the treatment of acute agitation associated with both bipolar mania and schizophrenia.

Sixty-five percent of hospital-based psychiatrists or emergency room physicians are not satisfied with current intramuscular antipsychotic therapies, primarily due to side effects that are difficult for patients to tolerate and because patients must be switched to a different oral therapy once they are stabilized, according to the Psychiatrist International Project conducted by PKS Research Partners in February 2004. In addition, 60 percent of these physicians said that currently available intramuscular treatments are not adequate in rapidly calming the agitated patient, which can help the physician to gain a patient's trust and cooperation.

"Acute agitation is terribly frightening and potentially dangerous for patients and their caregivers," said Barry Jones, M.D., professor of psychiatry, McMaster University, Toronto, Canada. "Zyprexa IntraMuscular enables doctors to help patients regain control quickly, often with just a single injection. Further, because Zyprexa IntraMuscular is not overly sedating, it can help the physician and patient to begin communicating and working together to achieve treatment goals and help move the patient's life forward."

Acute Agitation

Acute agitation is a well-recognized behavioral syndrome with a range of symptoms, including hostility, extreme excitement, poor impulse control, tension and uncooperativeness. The syndrome can occur with a number of conditions, including schizophrenia and bipolar disorder. Patients suffering from agitation in its severe forms are usually in an emergency situation and require immediate treatment to alleviate personal distress and to prevent harm to themselves and others.

Seamless Transition to Long-Term Therapy

FDA labeling for Zyprexa IntraMuscular specifically states that if ongoing Zyprexa therapy is needed, physicians may transition patients with schizophrenia and bipolar mania from Zyprexa IntraMuscular to oral Zyprexa as soon as clinically appropriate.

More than 56 percent of physicians say it is very important or important that an antipsychotic can be used in an injectable formulation for agitation and an oral formulation for long-term disease management.

"With Zyprexa IntraMuscular, physicians have a new option for treating agitation in schizophrenia and acute bipolar mania patients," said Mauricio Tohen, M.D., Dr.P.H., Lilly Distinguished Scholar. "We can offer highly agitated patients Zyprexa's dependable control from day one and then smoothly and assuredly transition them to oral Zyprexa for maintenance treatment."

Design and Results of Pivotal Trials

Zyprexa IntraMuscular's efficacy in controlling acute agitation was evaluated in three randomized, double-blind, placebo-controlled studies in patients with schizophrenia (two studies) and bipolar mania (one study). In these studies, the control of agitation with Zyprexa IntraMuscular was assessed using several scales, including the Positive and Negative Symptom Scale Excited Component (PANSS EC).

Using these scales, Zyprexa IntraMuscular was statistically superior to placebo in all studies. On the primary efficacy measure, the PANSS EC, 10 mg injections of Zyprexa IntraMuscular were significantly superior to placebo at the first time point measured (15 or 30 minutes) after injection

In the two studies in agitated patients with schizophrenia, Zyprexa IntraMuscular was compared to haloperidol (Haldol^®) intramuscular and to placebo. The injectable formation of haloperidol, a first generation or "typical" antipsychotic, has been the standard of care for acutely agitated patients for many years.

Results showed that both Zyprexa IntraMuscular and haloperidol intramuscular were superior to placebo. No adverse event occurred significantly more often with Zyprexa IntraMuscular than with haloperidol intramuscular. In fact, in these studies, painful muscle contractions called dystonia occurred in 6.6 percent of haloperidol intramuscular-treated patients, but did not occur with Zyprexa IntraMuscular. Additional side effects that occurred significantly more often with haloperidol intramuscular - but not with Zyprexa IntraMuscular - included tremors, muscle spasms, indigestion and blurred vision.

Zyprexa IntraMuscular was compared to lorazepam (Ativan^®) intramuscular and to placebo in the study involving agitated patients with bipolar mania. Lorazepam, which is an anti-anxiety, sedative and anticonvulsant medication, also has been used for decades. In this study, Zyprexa IntraMuscular was superior to placebo. No adverse event occurred significantly more often with Zyprexa IntraMuscular than with lorazepam intramuscular. In contrast, nausea and vomiting were reported significantly more often in lorazepam intramuscular-treated patients than in Zyprexa IntraMuscular-treated patients.