by Phyllis Vine

A report comparing the generic antidepressant, Budeprion XL 300, to the originally approved Wellbutrin XL 300 , found a significant difference in the behavior of the drugs. Basically the Teva generic released four times faster in the first two hours than did the GlaxoSmithKlein tablet. In another two hours, nearly half of the ingredients had been released, twice that of Wellbutrin. As a result, the benefit of the steady state of the extended release was lost.

The difference was documented by ConsumerLab following patient reports of the onset of worrisome symptoms when switched to Budeprion XL 300. The report is on their website, ConsumerLab.com (subscription required).

ConsumerLab's findings challenge confidence for those who depend on generic medication, especially people with a mental illness whose symptoms are subtle and subjective.

Doubts emerge
Doubts about the equivalence of the Budeprion XL 300 with Wellbutrin 300 XL began to surface on a web site, People's Pharmacy, where visitors find information and conversation about drugs. Joe and Terry Graedon, syndicated columnists, host the site and they began hearing from people who described a surge of symptoms including headaches, despair, anxiety, suicidal thoughts, night sweats, and disorganized thinking when taking Budeprion XL 300.

Two elements play a role in a drug's action. One is the active ingredients, in this instance buproprion. The other is the mechanism by which it is released into the body, called the "delivery technology." Tests performed by ConsumerLab revealed that Teva's Budeprion XL 300 released differently.

"We rarely get that many complaints about drugs with that many similarities," Joe Graedon told MIWatch. "They're saying they're anxious. Depression has come back with a vengeance, people are telling me. And they're crying and irritable."

"Something was odd," he thought to himself. Graedon, a pharmacologist, and his wife, Terry, a medical anthropologist, have co-authored numerous books about drugs, interactions and how consumers can make sense of what they buy. They were early champions of generics when few people trusted them. Then six years ago he began hearing about problems with generic drugs. When the letters began to cascade about Budeprion XL 300, he wondered, "Is this an orchestrated campaign?"

Patients who had done well on Wellbutrin XL 300 reported a decline when they started taking Budeprion XL 300. After the Graedons mentioned this on their syndicated radio show and newspaper column, "the flood gates opened up." He stopped counting after 250 comments arrived.

Because he feared the complaints he was receiving came from a contaminant, Graedon contacted the Food and Drug Administration (FDA). Then he contacted Tod Cooperman, MD, president of ConsumerLab.

FDA slow to respond
As of Nov. 3, there is nothing on the FDA's web site to inform consumers about the findings. Nor is there mention on MedWatch, the official site for registering complaints. In response to an email from MIWatch, FDA spokesperson Sandy Walsh replied, "We don't yet have a specific plan or timeline." FDANews carried the story ten days after MSNBC/Newsweek reported it on October 12.

The FDA maintains that "generic drugs are identical to their brand-name counterparts in dosage form, safety, strength, route of administration, quality, performance, and intended use. Generics also go through a rigorous scientific review to ensure both safety and effectiveness.” When asked to provide results of the analysis of Budeprion XL 300, a spokesperson said she would look into what information was publicly available.

The story has gotten play in the business community where a spokesman for Impax, the company actually making the drug, told Dow Jones, "Our studies were very good, and we were very satisfied with them, and by receiving that approval so was the FDA."

It's also inescapable in third-quarter earning reports. Not surprising, sales of Wellbutrin fell after a generic competitor hit the market. According to the Motley Fool, the sales of Wellbutrin XL, “slipped from $364 million in the fourth quarter of last year to just $231 million.” Of Teva? Business Wire reported that the Israeli company "had 150 abbreviated new drug applications awaiting final FDA approval. Collectively, the brand products covered by these applications have annual U.S. sales of approximately $88 billion."

More than a business story
Truth is, this is much more than a business story. It relates to the reliability of the pharmaceutical industry, to FDA procedures for approving and monitoring drug safety, and to the health of all who expect a generic drug to equal the patented.

"This information shatters the myth that generics are always identical to the original and it questions the belief that generics are always equivalent," said Cooperman.

Not just antidepressants
Graedon worries that the problem with Budeprion XL 300 pinpoints a larger problem with market forces pointing to generics, already a multi-billion dollar industry. A number of drugs are coming off patent, and the government as well as insurance companies see generics as cost-saving. Graedon likens the ConsumerLab results to a house of cards where consumers have been told they can trust the FDA’s guarantees of safety. "If the FDA approved it, if rules and regulations allowed this degree of flexibility," Graedon said, "it throws into question the entire approval process."

*photo from ConsumerLab.com