Eli Lilly may face problems getting approval for a new formulation of its blockbuster Zyprexa after staff reviewers at the US Food and Drug Administration issued documents expressing concern about the safety profile of the new treatment.

The reviewers said that a long-acting injectable form of Zyprexa (olanzapine), which will be called Zyprexa Adhera, is effective for the acute and long-term treatment of schizophrenia and is "acceptably safe”. However they are worried about "excessive sedation events” suffered by 24 out of 1,915 patients who received the jab, which is injected into the muscle.

The FDA staff noted that such events, though few in number, “are a serious safety concern because of the severity of excessive sedation, the unpredictable characteristics, and relatively high incidence". The profound sedation effect typically lasted about one to three hours and two of the patients were described as “coma” cases. However, all patients fully recovered within three to 72 hours.

The agency reviewers, which said that sedation appears unique to the injectable rather than the well-established oral form of the drug, concluded by saying that they would ask the Psychopharmalogic Drugs Advisory committee, which will meet to decide on approval on Wednesday, if Zyprexa Adhera needs a ‘black-box’ warning or if it should be designated as a second-choice drug.

Lilly responded by saying that "although there are important additional safety considerations associated with the injection, they are manageable with appropriate labelling and risk-minimisation activities”. It added that “many patients have decided that the risks are offset by robust symptom improvement, ensured medication delivery and flexibility in the dose”.

Sales of Zyprexa in its oral and short-acting injection forms were almost $4.8 billion in 2007 sales. Analysts believe that the long-acting formulation could top $1 billion.