An early magazine advertisement for Merck’s breakthrough asthma and allergy medicine, Singulair, featured a happy child, hanging upside-down from a tree.
Asthmatic kids could now breathe easier, the text assured, and side effects were “usually mild” and “similar to a sugar pill.”
When the drug launched in 1998, its label said the drug’s distribution in the brain was “minimal,” with no mention of psychiatric side effects.
Photo: Reuters
Merck’s early safety claims later faced intense scrutiny amid reports over two decades that patients, including many children, had died by suicide or experienced neuropsychiatric problems after taking the drug.
The US Food and Drug Administration (FDA) in 2020 ordered its most serious warning, known as a “black box,” on Singulair’s label. Merck now faces a raft of lawsuits alleging it knew from its early research that the drug could impact the brain and that it minimized the potential for psychiatric problems in statements to regulators.
The lawsuits cite the research of Julia Marschallinger, a cell biologist who has studied the drug along with colleagues at the Institute of Molecular Regenerative Medicine in Austria. The team in 2015 found that the drug’s distribution into the brain was more significant than its label described.
The FDA cited Marschallinger’s work when it ordered Singlair’s black-box warning label.
In its original patent for Singulair, Merck cited other applications for the drug, beyond asthma and allergies, including as a treatment for “cerebral spasm,” a neurological condition. Lawsuits filed against Merck cite this 1996 patent as evidence of Merck’s knowledge of the drug’s potential brain impacts.
Merck declined to comment for this report.
When Merck first sought FDA approval for Singulair, an FDA analyst, relying on company assertions, said in 1998 that “only a trace amount” of the drug could be found in the brain, federal documents show.
The FDA said Merck’s data showed the presence of the Singulair “declined over time” in all tissues.
Marschallinger and her colleagues in Austria came away with a different finding when they reviewed Merck’s original research and did some of their own. They started looking at Singulair as a potential dementia treatment in 2011. They became interested in that prospect in part because of the reports of psychiatric side effects, such as depression, agitation or hallucinations, from patients and medical providers.
While troubling, the side effects showed the drug might affect the brain. The researchers wanted to understand if it could benefit older patients with dementia.
In 2014, the scientists in Austria reanalyzed Merck’s original animal studies and noticed the drug decreased almost everywhere in the body 24 hours after dosage — but not in the brain, where it increased over this period, surpassing the amount in the blood and the lungs.
Marschallinger reported finding a “substantial amount” of the drug had reached the brain, in contrast to Merck’s description of the brain distribution as “minimal.”
The FDA said Merck’s original animal studies were “quite limited and cannot provide any definitive information about the montelukast levels and activity in the brain.” The agency acknowledged that its reviewer’s description that drug levels declined over time in all tissues “did not fully reflect the data.”
As for Marschallinger’s finding that a “substantial amount” of the drug had reached the brain, the FDA called it “a subjective characterization that is not necessarily incompatible with the ‘minimal’ descriptor in other contexts.”
The researchers’ 2015 study provided additional evidence that the drug reached the brain, but did not show any specific harm, the FDA said.
Marschallinger said it would have been logical for the FDA to require Merck to investigate the brain impacts more thoroughly once reports of mental-health problems emerged.
“The FDA could have asked Merck to repeat the experiment or do it for an even longer period of time,” Marschallinger said. “It’s not hard to do this.”
Seven people sustained mostly minor injuries in an airplane fire in South Korea, authorities said yesterday, with local media suggesting the blaze might have been caused by a portable battery stored in the overhead bin. The Air Busan plane, an Airbus A321, was set to fly to Hong Kong from Gimhae International Airport in southeastern Busan, but caught fire in the rear section on Tuesday night, the South Korean Ministry of Land, Infrastructure and Transport said. A total of 169 passengers and seven flight attendants and staff were evacuated down inflatable slides, it said. Authorities initially reported three injuries, but revised the number
‘BALD-FACED LIE’: The woman is accused of administering non-prescribed drugs to the one-year-old and filmed the toddler’s distress to solicit donations online A social media influencer accused of filming the torture of her baby to gain money allegedly manufactured symptoms causing the toddler to have brain surgery, a magistrate has heard. The 34-year-old Queensland woman is charged with torturing an infant and posting videos of the little girl online to build a social media following and solicit donations. A decision on her bail application in a Brisbane court was yesterday postponed after the magistrate opted to take more time before making a decision in an effort “not to be overwhelmed” by the nature of allegations “so offensive to right-thinking people.” The Sunshine Coast woman —
BORDER SERVICES: With the US-funded International Rescue Committee telling clinics to shut by tomorrow, Burmese refugees face sudden discharge from Thai hospitals Healthcare centers serving tens of thousands of refugees on the Thai-Myanmar border have been ordered shut after US President Donald Trump froze most foreign aid last week, forcing Thai officials to transport the sickest patients to other facilities. The International Rescue Committee (IRC), which funds the clinics with US support, told the facilities to shut by tomorrow, a local official and two camp committee members said. The IRC did not respond to a request for comment. Trump last week paused development assistance from the US Agency for International Development for 90 days to assess compatibility with his “America First” policy. The freeze has thrown
TESTING BAN: Satellite photos show a facility in the Chinese city of Mianyang that could aid nuclear weapons design and power generation, a US researcher said China appears to be building a large laser-ignited fusion research center in the southwestern city of Mianyang, experts at two analytical organizations said, a development that could aid nuclear weapons design and work exploring power generation. Satellite photos show four outlying “arms” that would house laser bays, and a central experiment bay that would hold a target chamber containing hydrogen isotopes the powerful lasers would fuse together, producing energy, said Decker Eveleth, a researcher at US-based independent research organization CNA Corp. It is a similar layout to the US$3.5 billion US National Ignition Facility (NIF) in northern California, which in 2022 generated
RSS