The Food and Drug Administration took a highly unusual step this week: It acknowledged that a widely used generic drug -- a copycat of the antidepressant Wellbutrin XL -- was not the equivalent of the original drug produced by GlaxoSmithKline since 2003.
The move prompted the world’s largest manufacturer of generic drugs, Israel-based Teva Pharmaceuticals, to stop shipping its generic extended-release bupropion -- marketed as Budeprion 300 mg XL-- and to remove it from U.S. shelves.
The FDA finding marks an about-face for the food and drug safety agency, which in 2009 responded to public concerns by flatly declaring Teva’s Budeprion XL “bioequivalent and therapeutically equivalent to (interchangeable with) Wellbutrin XL 300 mg.”
The agency’s reversal came after a five-year kerfuffle that has called into question its unqualified assertion that all generic medications work exactly as the more costly “pioneer drugs” they are intended to mimic. With millions of American patients switched -- often without notification -- to newer, cheaper forms of the drugs they take, this week’s acknowledgment by the FDA may open a small chink on the agency’s so-far impenetrable armor on generic drugs.
“The FDA is not infallible,” write Joe and Terry Graedon, who publish the column “The People’s Pharmacy,” and run an online forum by the same name. “Just because the agency says all generic drugs are identical to their brand-name counterparts does not make it so.”
The Graedons, whose column long ran in The Los Angeles Times, say they have also collected “a great many other complaints” about the generic forms of the beta-blocker Toprol XL (metaprolol) and the anti-seizure drug Keppra (levetiracitam), and have urged the FDA to look into them.
In recent years, a number of pharmacologists have raised concerns about the FDA’s standards for approving a range of generic medications -- concerns that the agency has turned away with the unbending assertion that all generics on the market are “the same as those brand-name drugs in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.”
In calling for the removal of Teva’s Budeprion XL this week, the FDA also called on four other generic manufacturers making extended-release forms of Wellbutrin to conduct tests demonstrating that they meet the agency’s standards for bioequivalence. Those generic drug-makers are Anchen, Activis, Mylan and Watson.
Last year, the FDA approved the first generic version of the antidepressant Lexapro. In 2010, the agency opened the door to generic versions of the extended-release antidepressant Effexor.
Read more about concerns raised about generics here: Just as good? Generic drugs save money, but there’s a growing clamor from patients and doctors that some aren’t as effective as their brand-name brethren.
In the case of Budeprion XL, which appeared on the market in December 2006, hundreds of consumers within months began sharing their stories in online chat rooms and with drug watchdog groups: As pharmacies filled their brand-name Wellbutrin XL prescriptions with Teva’s new generic version of the antidepressant, patients whose depression had been well-managed quickly found their symptoms returning.
The Graedons turned to ConsumerLab.com with a request to evaluate the generic Budeprion. In October 2007, ConsumerLab.com released a report finding that the Teva product behaved in a markedly different way from Wellbutrin XL: It released its active ingredient in a large early burst -- a pattern that could give patients taking it suddens jolts of medication and leave them with too little medication in their systems by the end of the day.
The FDA, in the end, found pretty much the same thing: In addition to finding that Teva’s Budeprion XL 300 mg “failed to meet the FDA’s bioequivalence standards for a generic drug,” the FDA found that patients taking the generic ended up with 75% of the drug, on average, in their bloodstreams than those taking the brand-name drug.
Generic drugs are a bargain. According to the FDA, they cost 80% to 85% less than the brand-name drugs they copy. Through 2010, generic drugs have saved U.S. consumers $931 billion, according to the Generic Drug Manufacturers.
But some physicians and pharmacologists have warned that certain drugs may need stricter scrutiny to ensure that generic formulations work in the same way as the drugs they follow. In particular, the effectiveness of medications for which there is a fine line between too much and too little -- some blood-thinning drugs, anti-arrhythmics and seizure medications are examples -- may suffer when generic manufacturers devise different formulations to deliver those medications. Extended-release forms of any drug can also be tricky for generic manufacturers to get right.
Bottom line: When you’re dispensed a new prescription, check to see whether you’ve been switched to a generic or from a generic made by one manufacturer to one made by a different generic drug-maker; if you have, be attentive to new side effects, a return of symptoms or any change in your condition, whether it’s epilepsy, high blood pressure, depression or irregular heartbeat. If you notice something new, talk to your physician and suggest that he or she make a report to the FDA’s Medwatch system, which tracks drug-related “adverse events.”