The FDA will update the labels on 3 commercially-available leukotriene inhibitors to reflect post-marketing research findings that the asthma-fighters can precipitate neuropsychiatric events ranging from agitation to suicidal ideation.

Leukotrienes have become popular options for treating moderate to severe asthma.

They are usually used in conjunction with bronchodilators or inhaled steroid medications.

The new warnings will appear on the labels for Merk’s Singulair, AZ’s Accolate and Zyflo, which is made by Cornerstone Therapeutics.

Singulair dominates the category from a sales standpoint. First approved in 1998, the drug is Merck’s top revenue-producer with $4.3 billion in sales last year. The drug has been approved for both children and adults with asthma and for the treatment of certain allergies. The latter 2 are approved for asthma only.

Leukotrienes are produced by the body in response to inflammatory stimuli such as inhaled allergens.

“Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications,” read the posting on the FDA website.

Neuropsychiatric events that have been linked to leukotriene inhibitors include agitation, aggression, anxiousness, depression, hallucinations, dream abnormalities, insomnia, irritability, restlessness, suicidal ideation, suicide and tremor.

Merck released a statement saying it was “confident in the efficacy and safety of Singulair,” while adding it would revise the label as directed by the FDA.

Neuropsychiatric events other than sleep disorders and insomnia “were not commonly observed” in trial data provided by the drug makers, according to the FDA.

The FDA launched an investigation last year after receiving reports of mood and behavior changes in patients taking Singulair. It asked all 3 drug makers for all available post-marketing information, and made the call after completing that review.

Cancer research trials published in peer-reviewed journals tend to include a disproportionately small number of women, according to a study published in Cancer.

To reach this conclusion, Reshma Jagsi and her colleagues at the University of Michigan reviewed 661 prospective studies involving more than a million subjects who had non-gender specific cancers like those of the colon, head and neck, lung, brain and lymphomas.

“In the vast majority of studies we analyzed, fewer women were enrolled than we would expect given the proportion of women diagnosed with the type of cancer being studied,” Jagsi told BurrillReport.

Jagsi added, “we’re seeing it in all cancer types. We know there are biological differences between the sexes, as well as social and cultural differences. Studies need to assess whether there are differences in responses to treatment between women and men.”

The practice flies in the face of the NIH’s Revitalization Act of 1993, which highlighted the need to include women in research studies in numbers sufficient to support gender-specific subgroup analyses.

Government-funded studies did include slightly higher numbers of female participants: 41% of subjects in such trials were women, whereas only 37% of the subjects in non-government-funded studies were women.

The authors suggested several reasons for the discrepancy. For example, scientists tend to avoid including “vulnerable populations,” such as women of childbearing age in their studies. “By protecting them from research, we’re excluding them,” the scientists concluded.

Other barriers are thought to include a lack of information, fear, and a belief that the studies interfere with individual responsibilities including child care.

The authors suggest that among other things, investigators should reimburse participants for transportation and child care expenses incurred during the study.