Singulair (montelukast) goes generic (FDA)

The FDA announced earlier this month that it granted approval to 10 generic manufacturers to produce and market generic forms of montelukast, sold by Merck since its approval in 1998 as Singulair. Brand-name Singulair currently costs about $168 per month, so cost competition could bring considerable savings to those taking the medication (and their insurance companies). Montelukast is a leukotriene receptor antagonist with FDA approved indications for long-term treatment of asthma in anyone over 1 year old, outdoor allergies in anyone older than 2, and indoor allergies in people aged 6 months and older. Singulair/montelukast is available in oral form, unlike almost all other asthma controller medications, which are inhaled. The 10 firms who will initially be allowed to sell generic Singulair are Apotex, Aurobindo Pharma, Endo, Glenmark Generics, Kudco Ireland, Mylan, Roxane Laboratories, Sandoz, Teva, and Torrent. What's montelukast good for, anyway? Singulair was better than placebo as first-line controller therapy for asthma in clinical trials, improving lung function (FEV1) by about 10-15%, reducing asthma symptoms, need for rescue albuterol, and asthma exacerbations. Overall, when tested against inhaled corticosteroids, montelukast was slightly inferior on most measures, in most trials. But in a few trials, it was equally good as inhaled steroids at controlling asthma symptoms and improving lung function. Furthermore, most of inhaled steroids' superiority is in improving objective measures such as lung function (which patients may or may not notice); when considering patient-centered outcomes like daily symptoms and quality of life, montelukast came out about equal to inhaled glucocorticoid as a first-line asthma controller medication, from clinical trials. Experts postulate that this could be due to easier adherence with taking a daily pill, compared to patients' notoriously low adherence rate with inhaled steroids. All this is why Marc Peters-Golden gave montelukast a cautious endorsement as an alternative first-line asthma therapy in his UpToDate topic review on the drug: "While not the preferred choice based upon efficacy in study populations, anti-leukotrienes may be considered a reasonable first-line controller agent for patients who either will not take or cannot tolerate inhaled GC."

But most physicians are probably not prescribing montelukast as first-line replacement for inhaled steroids, but rather in addition to them as so-called "step-up" therapy. There is good evidence for Singulair's efficacy when used in this manner, but in most studies it was not quite as effective as a long-acting beta agonist (LABA) added to inhaled steroids. In a few studies, montelukast was equi-efficacious to LABAs as add-on therapy, and there seem to be many patients in whom Singulair works very well, likely due to heterogeneity not only in response to montelukast, but in response to the inhaled therapies too.

Other specific situations in which there is evidence for montelukast's efficacy over other agents include aspirin-sensitive asthma, exercise-induced asthma, and viral upper respiratory infection-induced bronchospasm in children. Singulair has had some interesting side effects, including these mentioned on its web site: "SINGULAIR may cause serious side effects. Behavior and mood-related changes have been reported: agitation including aggressive behavior or hostility, bad or vivid dreams, depression, disorientation (confusion), feeling anxious, hallucinations (seeing or hearing things that are not really there), irritability, restlessness, sleepwalking, suicidal thoughts and actions (including suicide), tremor, and trouble sleeping." Other adverse effects mentioned by the FDA were feelings of "pins and needles" or numbness in the arms or legs; rash; flu-like symptoms; and severe pain and swelling of the sinuses. These are relatively uncommon, though. More frequent side effects reported from clinical trials were upper respiratory infection, fever, headache, sore throat, cough, stomach pain, diarrhea, ear ache, flu, runny nose, and sinus infection, the FDA said. At this writing, generic Singular / montelukast is not yet available in pharmacies, and no one knows when it will be (check Drugs.com for updates). Anyone who tries to sell you some right now is playing you -- like these "Canadian" guys (don't buy from them).