A Reuters report on Friday revealed that FDA researchers have found additional molecular evidence tying blockbuster asthma therapy montelukast to adverse neuropsychiatric effects.
FDA researchers have found new evidence of a molecular link between Merck’s former blockbuster asthma drug montelukast—which is now marketed by spinoff Organon under the brand name Singulair—with neuropsychiatric problems, according to a Friday report from Reuters.
The regulator’s research, presented Wednesday at the 2024 Annual Meeting of the American College of Toxicology, found multiple off-target effects of montelukast on G-protein coupled receptors and neurotransmitter transporters in the brain, which are involved in various psychiatric pathways. The FDA’s presentation also noted that montelukast can penetrate into the brains of rats, validating prior research.
“Emerging data from confirmatory pharmacology studies in primary human CNS cells treated with montelukast and endogenous receptor ligands provide further insight into potential molecular mechanisms of drug-related [central nervous system] effects,” the researchers wrote in their abstract. “This report is the first public release” of these findings.
According to Reuters, the FDA does not intend to update the label of montelukast products to reflect these latest findings.
Montelukast is a small molecule blocker of leukotriene receptors, which are typically found in the airway and induce bronchoconstriction when activated by their corresponding ligands. With its mechanism of action, montelukast helps combat the symptoms of asthma and allergic rhinitis. The drug first won the FDA’s approval in 1998 and hit the market with the brand name Singulair.
In the following years, Singulair became one of Merck’s top-selling drugs, bringing in more than $1.4 billion in 2001 and racking up nearly $50 billion in sales throughout its lifetime, according to a 2017 Kiplinger analysis.
By 2019, however, the FDA had flagged thousands of neuropsychiatric adverse events in patients taking Singulair and other generic montelukast products. At the time, Merck faced strong backlash for allegedly minimizing early signs of this safety risk. When the pharma launched Singulair, it claimed that side effects were mostly mild.
These reports pushed the regulator to add a black box warning for the drug in 2020. This warning alerts patients and prescribers to the risk of “serious neuropsychiatric events” including agitation, hostility, depression, anxiousness, insomnia and obsessive-compulsive symptoms. Some patients on montelukast have also developed suicidal thoughts and behaviors.
Because of these risks, the benefits of Singulair—or montelukast more broadly—may no longer outweigh its risk in allergic rhinitis, according to its label, which recommends to reserve its use for patients who have “inadequate response or intolerance” to other therapies.
The drug moved over to Organon when that unit spun out of Merck. Organon told Reuters in a statement that the product’s current label is appropriate regarding its “benefits, risks and reported adverse reactions.”
