Zyprexa's long-acting variant receives limited nod

A panel of external medical experts report Zyprexa's long-acting variant as "acceptably safe" in some schizophrenia patients while sharing FDA's concern about the risk of severe sedation due to injection.

Schizophrenia patients shall, henceforth, have an alternative line of treatment with the long-acting, injectable form of Zyprexa. It is a top-selling drug made by Eli Lilly & Co.

On Wednesday, the US FDA’s panel of external medical experts reported the drug as “acceptably safe” for use in certain patients.

While the unanimous opinion was the product was effective at treating schizophrenia, the members concurred with the FDA with respect to concerns about “profound sedation”. The patients who received the drug during the clinical studies were severely affected leading to loss of consciousness and coma. Therefore, ten voting members suggested the drug be approved for use in certain patients and one member abstained. The decision of the panel amounts to a restricted recommendation of the product by the FDA.

In the clinical studies, 2045 patients received the long-acting form of Zyprexa and 24 out of the above, or about 1%, suffered profound sedation after being injected. The FDA’s staff review stated the sedation lasted typically between one to three hours. At least two patients were in a coma after the injection. However, all patients fully recovered and most patients proceeded to receive additional injections.

The director of FDA’s psychiatry products division, Dr Thomas Laughren, noted the severe sedation was unique to the injectable form of Zyprexa. He added the long-acting form of Risperdal, of Johnson & Johnson showed no such side-effect. Other long-acting injections use traditional drugs like haloperidole and fluphenazine.

According to the experts, only patients with chronic non-compliance with oral medication should receive the long-acting form of Zyprexa. Data presented at the meeting showed patients with high rates of non-compliance with daily medication.

Currently, Zyprexa is approved for use as oral, once-daily medication to treat schizophrenia and bipolar disorder. It registered about $4.8 billion in sales last year. A short-acting injectable variant is also available. It is used to treat agitated and non-cooperative patients mainly in an emergency. Just as in the oral form, the long-acting form of Zyprexa also resulted in weight gain, changes in blood sugar and high cholesterol.

The prevalence of deep sedation as a side effect in about 1 in 100 patients in a relatively short time could be a significant public health risk. Therefore, the FDA had not come to a firm conclusion whether to approve the long-acting form of the drug. The agency had turned to the panel consisting of practitioners and psychiatrists from academic institutions. Some panel members suggested the product be approved as the probable second-line of treatment after attempting other treatments.

One panel member stated current injectable drugs did not elicit response in all patients and therefore, this form could be beneficial in such cases.

Schizophrenia is a chronic brain disorder in which patients show unpredictable thought processes. People with schizophrenia may believe other people are out to harm them or hear voices that those around cannot. There is a fatalistic behaviour pattern and patients are sure those around cannot be trusted. It could be a leading cause for depressiondefine and suicide in adolescents and adults.

The manufacturer was pleased with the committee’s recommendation and promised to continue to cooperate with the FDA in its review. It would continue to study the long-acting form of Zyprexa to track cases of severe sedation.

The medical director at Eli, Sara Corya, said the company would devise a risk-management program to advice clinicians to observe patients at one hour after the injection. It would also encourage the family or friends to observe for another two hours to help rush medical assistance if needed. The drug could be injected every two to four weeks in the doctor’s office.