Concerns mount over Singulair

This is an illustration of a young woman smiling and then grabbing her head as she experiences some type of mental health episode.

The Food and Drug Administration’s (FDA) Montelukast Working Group (MWG) has released its first public report on the potential neuropsychiatric effects of asthma and allergy drug, montelukast, commonly known by its brand name Singulair. The FDA presented preliminary results of the report at the American College of Toxicology’s annual meeting in Austin, Texas, in mid-November.

According to Jessica Oliphant, a deputy director at FDA's National Center for Toxicological Research, studies shedding light on the potential molecular mechanisms of montelukast's central nervous system (CNS) effects have drawn scrutiny from the medical community. Montelukast has been a staple in managing asthma symptoms for both pediatric and adult patients. However, its use has expanded beyond asthma, with off-label applications including the management of COVID-19 and migraines.

Despite its widespread use, concerns about neuropsychiatric adverse events have sparked global discussions among patient advocates, health care clinicians, media, lawmakers, industry and regulators. However, the link between montelukast and neuropsychiatric events remains unclear. The FDA MWG was established in 2019 to address these concerns, following a 2019 FDA Advisory Committee Meeting.

Initial studies by the MWG identified several candidate off-target G-protein coupled receptors (GPCRs) and neurotransmitter transporters in the brain that could be linked to neuropsychiatric safety concerns. These findings emerged from secondary pharmacology studies using radioligand binding assays and functional assessments.

Further insights have been gained from confirmatory pharmacology studies in primary human CNS cells treated with montelukast. These studies, along with a pharmacokinetic model developed to mimic clinically relevant exposure levels in rats, aim to evaluate montelukast-related CNS effects, drug exposure levels and CNS accumulation potential in vivo. 

This report marks the first public release of findings from the FDA MWG studies. As research continues, Oliphant told meeting attendees that the FDA remains committed to ensuring the safety and efficacy of medications for all patients.

Because of growing concerns, the FDA issued a Boxed Warning for Singular in 2022.

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