Five Years After ConsumerLab.com Reported a Problem, FDA Agrees Generic Version of Wellbutrin XL Is Not Equivalent and Is Pulled Off Market — Important Lessons about Generics

White Plains, New York — October 4, 2012 [Updated 10/11/12]— Are all generic drugs therapeutically equivalent to their brand name counterparts? Until yesterday, the FDA, and many others, adamantly said they were. In an unprecedented move Wednesday afternoon, the FDA admitted that a generic version of the popular antidepressant Wellbutrin XL 300 mg, marketed since 2006 as Budeprion XL 300 mg by Teva Pharmaceuticals, is not an equivalent drug, prompting Teva to stop shipping the product. ConsumerLab.com has warned consumers of a problem with Budeprion XL since it tested it in 2007 — a problem the FDA had gone out of its way to deny.

ConsumerLab.com's President, Tod Cooperman, M.D., believes that the generic's faster initial release of drug  and slower later release puts patients on an "unexpected roller coaster ride that never reaches its expected destination" rather than a "slow drive up to therapeutic levels" with the original drug. "The problem with Budeprion XL 300," according to Dr. Cooperman, is not the active ingredient, but the mechanism by which it is released from the pill, which is known to differ from the original product and can also vary from generic to generic."

A 5-year saga:
Shortly after release of Budeprion XL 300 mg in December 2006, consumers began reporting unusual side effects and a return of their depression. These reports alarmed syndicated columnists Joe and Terry Graedon of The People's Pharmacy, who asked ConsumerLab.com if it would investigate the issue. ConsumerLab.com purchased and tested the product. In its October 2007 report "Wellbutrin vs. Generic Bupropion," ConsumerLab.com noted that while Wellbutrin XL, a high-dose, once-a-day, special extended-release formula, gradually released its active ingredient, Budeprion XL released a large early burst of ingredient. In the first two hours of a dissolution test, ConsumerLab.com found Budeprion released 34% of the drug, while Wellbutrin released 8%. At four hours, the Teva product released nearly half of its ingredients, while original Wellbutrin released 25 percent. The generic did not act like a once-a-day formula but more like an immediate release formula.

Responding to mounting concerns about Budeprion XL 300, the FDA revealed in a 2009 report that the product had never undergone bioequivalence testing but, based on tests of a 150 mg version, it had approved the 300 mg version. Despite this stunning revelation, the FDA continued to consider the 300 mg version bioequivalent. ConsumerLab.com pointed out that labeling on Budeprion XL 300 mg claims not only that it has been tested but that its performance is identical to Wellbutrin XL. The FDA admitted that it was aware of this inaccuracy, noting that it requires performance information on all generics to match that of brand name counterparts.

Despite the FDA's continued support of the Budeprion XL 300 mg, it asked Teva in 2009 to voluntarily perform bioequivalence tests on the drug involving people who had reported problems. ConsumerLab.com and the People's Pharmacy, which had each been collecting reports from consumers, offered to contact these individuals to help recruit subjects, but neither the FDA nor Teva pursued the offer. Teva never completed the study, citing difficulty recruiting subjects.

In 2010, Dr. Gary Buehler, who had signed off on the original approval of Budeprion XL 300 while Director of the FDA's Office of Generic Drugs, left the agency, taking a position as a vice president at Teva.  That same year, the FDA decided to sponsor its own bioequivalence study comparing Budeprion XL 300 mg to Wellbutrin XL 300 mg. Results of that study are the basis for the FDA's pronouncement yesterday that "Budeprion XL 300 mg tablets fail to release bupropion into the blood at the same rate and to the same extent as Wellbutrin XL 300 mg." The FDA found with Budeprion XL 300 that the maximum concentration of drug in the blood reached only 75% of that with Wellbutrin XL 300. [Full bioequivalence test results, as well as dissolution results -- which match those by ConsumerLab.com, were posted by the FDA on 10/11/2012.]

Lessons for all:
What is a consumer, a doctor, a pharmacist, to make of all this? ConsumerLab.com's Dr. Cooperman suggests the following:

• If a generic doesn't work like the original drug, be concerned, particularly if it is an extended release (often called "XL") product.
• Be aware that the labeling on a generic drug describing its performance is copied from the labeling of the original product and may not reflect the performance of the generic. This is a deception required by the FDA, perhaps to create the perception of generics as interchangeable.
• If a generic works for you, look carefully at the label and identify the manufacturer. Request the same manufacturer each time you refill that prescription. Other generics may not behave the same way.
• Be aware than none of the other four generic bupropion hydrochloride XL 300 mg products have been tested for bioequivalence. The FDA is only now requesting this of the companies which make them — Anchen, Actavis, Watson, and Mylan.

"It is important that the FDA has finally owned up to the error it made with this product, but thousands of Americans have suffered in the meantime," said Dr. Cooperman. "While most generic drugs are probably fine, it is important to understand that generics are not tested for safety or efficacy. Consumers will be the first to know if there is a problem — not their doctors, pharmacists, nor the FDA."

ConsumerLab.com is a leading provider of consumer information and independent evaluations of products that affect health and nutrition, with online reports for over 900 products. The company is privately held and based in Westchester County, New York. It has no ownership from, or interest in, companies that manufacture, distribute, or sell consumer products. Membership to www.ConsumerLab.com is available online.



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