Montelukast is a leukotriene receptor antagonist
used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.
Montelukast comes as a tablet, a chewable tablet, and granules to take by mouth. Montelukast
is usually taken once a day with or without food. Montelukast is a CysLT1 antagonist;
it blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1
in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction
otherwise caused by the leukotriene and results in less inflammation.
Because of its method of operation, it is not useful for the treatment of acute asthma
attacks. Again because of its very specific mechanism of action, it does not interact
with other asthma medications such as theophylline. Another leukotriene receptor antagonist is
zafirlukast, taken twice daily. Zileuton, an asthma drug taken four times per day, blocks
leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway.
The Mont in Montelukast stands for Montreal, the place where Merck developed the drug. Medical uses
Montelukast is used for a number of conditions including asthma, exercise induced bronchospasm,
allergic rhinitis, and urticaria. It is mainly used as a complementary therapy in adults
in addition to inhaled corticosteroids, if they alone do not bring the desired effect.
Montelukast is administered as montelukast sodium, with 5.2 mg of montelukast sodium
being equivalent to 5 mg of montelukast. Adverse effects
Side effects include gastrointestinal disturbances, headaches, hypersensitivity reactions, sleep
disorders, and increased bleeding tendency, in addition to other generic adverse reactions.
Its use is associated with a higher incidence of Churg–Strauss syndrome. Drowsiness is
also a common side effect. FDA investigation
In March 2008, the U.S. Food and Drug Administration announced that it would investigate whether
mood changes and suicidal thoughts are possible side effects of drugs in this class, including
the popular drug Singulair, which currently lists these side effects.
On June 12, 2009, the FDA concluded their review into the possibility of neuropsychiatric
side effects with leukotriene modulator drugs. Although clinical trials only revealed an
increased risk of insomnia, post-marketing surveillance showed that the drugs are associated
with a possible increase in suicidal behavior and other side effects such as agitation,
aggression, anxiousness, dream abnormalities and hallucinations, depression, irritability,
restlessness, and tremor. Use with loratadine
Schering-Plough and Merck sought permission to market a combined tablet with loratadine
and montelukast, as many patients combine the two themselves. However, the FDA has found
no benefit from a combined pill for seasonal allergies over taking the two drugs in combination,
and on April 25, 2008, issued a “not approvable” letter for the combination.
Dosage and administration The usual dose of Montelukast in adults and
teenagers is one 10 mg tablet taken orally a day. In children 6 to 14 years of age the
usual dosage is one 5 mg chewable tablet a day.children 6 months to 6 years old 4 mg
granules once daily Patents
Singulair was covered by U.S. Patent No. 5,565,473 which expired on August 3, 2012. The same
day, the FDA approved several generic versions of montelukast.
The United States Patent and Trademark Office launched a reexamination of the patent covering
Singulair on May 28, 2009. The decision was driven by the discovery of references that
were not included in the original patent application process. The references were submitted through
Article One Partners, an online research community focused on finding literature relating to
existing patents. The references included a scientific article produced by a Merck employee
on the active ingredient in Singulair. A previously filed patent had been submitted in the same
technology area. Seven months later the U.S. Patent and Trademark Office determined that
the patent in question was valid based on the initial reexamination and new information
provided, submitting their decision on December 17, 2009.
References External links
U.S. National Library of Medicine: Drug Information Portal – Montelukast