US FDA asks for caution on Merck asthma drug

Merck & Co Inc’s top-selling drug Singulair and similar medicines should come with a caution about reports of psychiatric problems in some patients, U.S. regulators said on Friday.

The Food and Drug Administration said it had requested a precaution in the prescribing instructions for Singulair, AstraZeneca Plc’s Accolate and Cornerstone Therapeutics Inc’s Zyflo and Zyflo CR. A precaution is a less serious alert than a warning.

Problems that were reported include agitation, aggression, suicidal thinking, suicide, depression, insomnia and irritability, an FDA notice said.

Psychiatric problems were uncommon in clinical trials of the drugs but those data were limited because the studies were not designed evaluate those issues, the FDA said.

Some post-approval reports of psychiatric events “included clinical details consistent with a drug-induced effect,” the FDA added.

Doctors therefore should be aware mental issues could arise and consider discontinuing the drugs if patients develop psychiatric symptoms, the agency said.

Merck said in a statement it was confident in the safety of Singulair, which has been prescribed to tens of millions of patients with asthma and allergies since its approval in 1998.

The company said it would revise the drug label as requested. The types of problems the FDA cited already were mentioned in a less prominent section of the prescribing instructions.

Singulair is Merck’s biggest product with annual sales of $4.5 billion. The drug’s generic name is montelukast.

Morningstar analyst Damien Conover said the FDA request was only a “slight negative” for the pill because its possible link to suicidal thoughts and behavior has been known for some time and has hurt sales of the product for the past year.

“The news about neurological side effects is already out there; I wouldn’t expect it to have much impact,” said Conover, who noted that the side effects have deterred allergy patients from using the drug more so than asthma patients.

Singulair sales slipped 4 percent to $1.1 billion in the first quarter. The drug commands far higher revenue than rivals in the same class of medicines, which work by blocking inflammation-causing proteins called leukotrienes.

The FDA had announced in March 2008 it was reviewing safety data that raised concerns Singulair might be linked to suicidal behavior or mood-related side effects.

BMO Capital Markets analyst Robert Hazlett said the request for a precaution “was likely the best outcome” other than no change.

Hazlett, in a research note, estimated 2009 Singulair sales of $4.4 billion, adding “U.S. sales are estimated to be down 2 percent as lingering effects of the (FDA) review may modestly pressure prescription growth, which in turn could be offset by price increases. Sales growth is expected to return in 2010.”

AstraZeneca spokesman Blair Hains said the company was adding a precaution about reports of depression and insomnia to the label for Accolate, which had 2008 sales of $73 million worldwide. The drug’s generic name is zafirlukast.

Officials at Cornerstone Therapeutics could not immediately be reached for comment on Zyflo, known generically as zileuton.

The FDA notice was posted on the agency’s website at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166246.htm.

By Lisa Richwine
WASHINGTON (Reuters)