WASHINGTON — Federal investigators warned nearly five years ago that the diabetes drug Avandia might be causing heart failure, according to an internal government memo released Tuesday by a consumer group.
Investigators also raised concerns about Actos, a similar drug used to treat Type 2 diabetes.
Separately, in fast-moving developments in the latest drug safety investigation, a senior Republican senator said Tuesday he had learned that the Food and Drug Administration's safety office had recommended the strongest possible warning for Avandia -- only to be overruled.
"The FDA didn't take that advice," said Sen. Charles E. Grassley (R-Iowa), a critic of the agency. "Instead, the warning about congestive heart failure risks with this drug is currently buried."
FDA spokeswoman Julie Zawisza responded that debate and disagreement were not unusual within the agency, "particularly when the science is unclear, complex or emerging."
"We do not have sufficient understanding of the data at this time to make a regulatory decision," she said.
The FDA issued a safety alert about Avandia on Monday after a study in the New England Journal of Medicine linked the medication to increased risk of heart attacks and death from cardiac disease. The alert underscored less prominent warnings of heart risks in prescribing literature primarily intended for doctors.
But a memo from FDA drug safety reviewers -- dated July 16, 2002 -- indicates there were significant concerns much earlier within the agency about Avandia and Actos.
Released by the watchdog group Public Citizen, the memo analyzed 47 early reports to the FDA of patients who went into heart failure and had to be hospitalized while taking one of the drugs. Congestive heart failure, or CHF, is a life-threatening condition that comes about when the heart is unable to pump enough blood to the rest of the body.
"This case series strongly supports the hypothesis that [these drugs], as a class, may be associated with CHF in diabetics," the memo said. The safety reviewers went on to recommend changes in prescribing information to alert doctors to their findings, as well as follow-up studies to definitively resolve suspicions.
"With this kind of evidence in 2002, there should have been a sharp decrease in the prescribing of these drugs," said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group. "Instead, just the opposite happened."
