Generic Drugs: Dangerous Differences?

"I would say that while differences in in vitro dissolution tests raise some concern. The real gold standard is how the products release and blood levels achieved in humans," agreed James Stevenson, director of pharmacy services at the University of Michigan Health System College of Pharmacy in Ann Arbor.

"Unless there are data showing clinical differences in drug release and blood levels I would be cautious in drawing any conclusions," he said. "It sounds like some more clinical testing might be in order to fully answer this concern."

In response, Cooperman admits blood-level tests could provide useful data. "But," he noted, "as the active ingredient is known to be rapidly and well absorbed, it's likely that you would again see that much of the drug from the [generic] product enters the blood sooner than Wellbutrin."

Cooperman said that even if blood level studies were performed, the Food and Drug Administration allows a certain level of variation in these tests between brand-name products and their generic versions.

"Even if within those bounds those limits may not have been appropriate in the first place to say that the drug is truly equivalent," he said. "In short, even a blood-level study may not be definitive.

Time Release Concerns

Throughout the course of's investigation, there was never a doubt that the generic bupropion studied had the same amount of the same active ingredient contained in Wellbutrin. It was only the rate of release that researchers said differed. But for some patients, doctors said, these differences can be important ones.

"For most drugs, there's very little concern about the equivalence of brand and generic drugs or about equivalence of different generic drugs; the active ingredients are absolutely identical," said Dr. Gregory Simon, psychiatrist and researcher at the Group Health Cooperative in Seattle. "But there is more concern about equivalence for slow-release or sustained-release formulations. These can vary between manufacturers -- either in how rapidly the drug is released or how completely it is released.

"If a drug is released more rapidly, there can be more side effects. If it's not released completely, it can be less effective."

In the case of bupropion, the time-release mechanism of the name-brand Wellbutrin was still patent-protected, meaning that generic purveyors were forced to develop slightly different means of delivering the same active ingredient.

"Sustained release mechanisms are not that easy to develop, and they tend to be proprietary in nature," said Michael Katz, clinical associate professor of pharmacy practice and science at the University of Arizona College of Pharmacy in Tucson.

"It would be difficult for a generic manufacturer to reproduce the same release characteristics as the brand-name product," he continued. "Such differences clearly could have an impact on patients who may switch from one product to another, and my view is that sustained-release products are among the relatively short list of products that should not be switched."

Time-release issues may not be exclusive to psychiatric drugs.

"In our field -- ophthalmology -- generic suspensions where drug release can be very variable is often a concern," said Dr. Randall Olson, director of the University of Utah's John A. Moran Eye Center in Salt Lake City. "Clearly, generics may not measure up at times, so buyer beware."

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