Concern over Actos Has Existed for Some Time

Washington, DCRecent concerns with regard to Actos side effects mirror previous warnings that are at least a decade old but have become lost in the Avandia issue and the swing by Avandia patients to Actos—a diabetes drug in the same class as Avandia but considered less dangerous. Sales of Actos have risen exponentially as concern over Avandia increased.

However, Actos (pioglitazone hydrochloride, manufactured by Takeda Pharmaceuticals) is beset with its own set of problems, including risk for congestive heart failure (Actos heart failure) and complications involving the liver. And something else that is now on the radar of the US Food and Drug Administration (FDA) is the potential for Rhabdomyolysis—a relatively rare condition characterized by the deterioration of muscle fibers and the release of myoglobin into the bloodstream.

Rhabdomyolysis can lead to kidney failure. Bladder cancer is also on the list of potential Actos adverse reactions the FDA is studying.

Concern over such things as Actos congestive heart failure et al must come as a shock to the population at large, especially in view of the swing away from rosiglitazone (Avandia) to pioglitazone (Actos). In anticipation of a scheduled meeting of an FDA advisory panel on Avandia last summer (from which new restrictions on Avandia emerged), Sr. Sydney Wolfe of the advocacy group Public Citizen was petitioning the FDA for an outright ban on Avandia. On April 28 of last year, Wolfe noted, at least, that Actos had neither increased nor decreased cardiovascular risk in six randomized trials.

There is little doubt that Actos has benefitted the most from the diminished fortunes of rosiglitazone. Sales for pioglitazone are now in the billions as the diabetes drug assumes the role Avandia once had.

However, Actos appears to have its own imposing booth at the drug side effects trade show. Almost lost in the rosiglitazone-bashing by Public Citizen last April was an observation that "of all the drugs evaluated, metformin hydrochloride was the only drug associated with a decreased risk of cardiovascular mortality compared with any other oral diabetes agent or placebo…" according to the Public Citizen petition.

What's more, anyone surprised to hear of concern for the Actos diabetes drug need only look back to a presentation by Public Citizen in March of 2000 with regard to what it saw as "inadequate, misleading, and potentially dangerous professional product labeling for the thiazolidinediones or 'glitazone' diabetes drugs: troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos).

"The glitazone drugs are approved as adjuncts to diet and exercise to improve blood sugar control in patients with type 2 diabetes. However, their labels are inadequate and fail to mention or explain some important safety and efficacy information that appear to be class effects that apply to all three drugs in this class."

We all know about Avandia. But on March 7, 2000 (almost 11 years ago to the day), Public Citizen was acknowledging the fact that Actos had caused death from heart dysfunction in rats. It was also noted that in relation to Actos and heart failure, pioglitazone was identified as having potential to cause cardiomegaly—a potential that was anticipated from preclinical studies.

"For this reason," stated Public Citizen, "the sponsor performed a 26-week echocardiogram study in diabetics (those without valvular abnormalities, ischemic heart disease, or symptomatic heart failure). Four doses of pioglitazone were compared with placebo. The Medical Officer concluded that, 'The results of this [echocardiogram] study provide little, if any reassurance that PIO [pioglitazone, Actos] does not damage the heart.'"

In summary, many who have been switched to Actos following concern over Avandia during the last few years—or anyone who has followed the emphasis placed on Actos as a safer alternative to Avandia—will be surprised to hear that Actos carries its own set of risks, Actos liver and Actos CHF among them. But as noted above, concern has been out there for some time.