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Montelukast (Singulair) should not be allowed over-the-counter use for hay fever and other upper respiratory allergy symptoms, an FDA advisory panel recommended Friday.

The advisors voted 11-to-4 against a risk-benefit ratio supportive of OTC use to treat nasal congestion, runny nose, itchy, watery eyes, sneezing, and itching of the nose in adults.

The vote was likewise 11 no's versus 4 yes's that OTC use would be safe, considering the potential for off-label use if the FDA followed a positive recommendation from the advisory committee, which it usually does.

The partial switch from prescription to OTC use (trade name Singulair Allergy) was proposed only for adults at the once-daily 10 mg dose, while the drug would remain under prescription for the currently approved indication for seasonal allergic rhinitis in children as young as 2 years and older and for perennial allergic rhinitis in those as young as 6 months.

However, a substantial proportion of current prescription use is in children, which the panel expressed concern could mean unintended OTC use in that group.

A study in adolescents ages 15 to 17 submitted by drugmaker Merck to support the application showed that too many teens thought it was right for them to use, despite labeling only for adults.

The lower bound came in at 80% correct answers versus the target of over 90%, although the teens did meet targets for comprehension of warnings for neuropsychiatric events.

That risk was also a concern discussed by the panel.

Montelukast poses a significantly greater risk than existing over-the-counter allergy medications, , argued during the open public hearing portion of the discussion.

"Among the side effects: agitation, aggressive behavior, anxiety, depression, hallucinations, insomnia, irritability and suicidal thoughts," he warned. "If people could buy Singulair without a prescription, the potential for inappropriate and potentially dangerous use is high."

While montelukast is otherwise generally safe, "you can imagine that would be concerning for a physician to not be aware of if it was happening to their patient," , director of the adult allergy program at the University of Arizona College of Medicine in Tucson, agreed in an interview with 乌鸦传媒.

A label comprehension study in adults with allergic rhinitis showed that nearly all understood the warnings about changes in mood, behavior, or thoughts or changes in sleep that the , both questions meeting the 90% threshold for lower bound.

Montelukast would have been the first in the leukotriene receptor antagonist class to make the switch from prescription to OTC.

Other OTC treatments for allergic rhinitis include oral antihistamines, oral combinations of an antihistamine and decongestant, intranasal decongestants, intranasal cromolyn, and an intranasal corticosteroid.

Having another class of drugs available would be an advantage for patients, George Philip, MD, an allergist and executive director of clinical research and product development at Merck.

He cited studies showing that nearly 40% of allergy patients switch among medications, and about a quarter aren't satisfied with their medication.

"Over-the-counter therapies have been playing an increasingly important role," he told 乌鸦传媒 in advance of representing the drug before the panel. "Based on the labeling of those products, not all currently available OTC products are right for all consumers."

Moreover, for patients, cost is a barrier to use, commented , chair of allergy and clinical immunology at the Cleveland Clinic.

"When medications go over the counter, frequently the cost goes down, it becomes more affordable, and more individuals have access to the drug," he told 乌鸦传媒.

The bigger concern for the panel, though, was montelukast would have been the first OTC drug that's also an approved asthma controller medication.

Although proposed to remain under prescription for that indication, off-label use and the considerable overlap between the two conditions raised the complexity of the decision.

Up to 40% of allergic rhinitis patients are also estimated to have asthma; while up to 90% of asthma patients have allergic rhinitis.

"The concern is that the use of the drug by patients in an unrestricted fashion may extend beyond allergic rhinitis, specifically that patients may self-medicate and treat their asthma and delay seeking medical care and get into trouble with their asthma," Lang explained.

The self-selection and label comprehension study in adults with asthma showed that the majority of patients correctly selected themselves for use by allergic rhinitis status, but the target of a lower bound of at least 90% correct answers wasn't met for understanding that the drug should not be used to treat asthma.

Merck also asked that the OTC indication include "itchy, watery eyes," which has not been part of the existing prescription labeling.

The evidence to support an ocular indication came from post-hoc analysis of a secondary endpoint in three seasonal allergic rhinitis trials.

Only one of the three trials showed a significant improvement in daytime eye symptom score (an average of tearing, itchy, and red and puffy eyes), and that improvement had an effect size of 0.14.

"It is unclear whether the small change represents a clinically meaningful improvement," the FDA staff review noted.

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