Maybe Sometimes the Brand Name Drug Does Work Better
I’m a huge skeptic of a lot of things, but in this particular instance it is a patient’s insistence that brand name drugs work better than their generic equivalents. I mistakenly believed that the FDA had bioequivalency requirements and testing in place that ensured that the generic versions were just as effective as the original. I was not however aware of the FDA practice of extrapolating results for different dosages. Now I am left wondering how many times I have questioned a claimant’s sincerity when insisting that they needed the brand name drugs because they work better. It doesn’t happen much, which is why it bothers me so, but here’s the trigger for this guilt trip.
On October 3, 2012, the FDA asked Teva Pharmaceuticals to voluntarily withdraw its generic version of the popular antidepressant, Wellbutrin XL 300. As it turns out, its Budeprion XL 300 is not the therapeutic equivalent, apparently releasing its key ingredient faster than the original drug. Interestingly, this fact has been known since 2007. During the first 6 months on the market, the FDA received 85 post-marketing reports of patients who had switched to the generic, experiencing undesirable aide effects. ConsumerLab published an analysis in 2007 of the two drugs and found that the Teva generic released 34% of its active ingredient in 2 hours whereas the brand name released only 8%. This would attribute for the reported side effects such as headaches, anxiety and insomnia. So how did this happen and why did it take the FDA 5 years to take action?
The FDA approved Teva’s Budeprion XL in 2006 on the basis that there was no significant difference in the rate and extent of absorption as measured by the plasma bupropion concentrations between 150 mg of the Teva XL product and 150 mg of Wellbutrin XL. The 300 mg strength, however, was not studied because of the potential risk of seizures at higher doses. This practice is common when evaluating the pharmacokinetic profile of a drug in normal volunteers, especially when a drug’s adverse effects increase with the dose. The pharmacokinetic profile was not expected to differ between 300 mg and 150 mg doses of extended release budeprion, therefore the results were extrapolated to establish bioequivalence of the 300 mg product. Apparently they were wrong as the FDA now admits that this generic is not the therapeutic equivalent to the brand name drug and that practice of extrapolating is no longer appropriate.
In 2010, the FDA finally decided to sponsor a bioequivalence study measuring the rate and extent of release into the blood for 24 healthy adults. The results, which became available in August 2012, indicated that Teva’s generic failed to release bupropion at the same rate and to the same extent as the brand name drug. Note that of the 4 other manufacturers of generic Wellbutrin XL 300 (Anchen, Actavis, Watson, and Mylan), none have reported similar side effects, yet have also not been tested for bioequivalence. In light of the Teva findings, the FDA has asked that each company conduct its own study and submit data from those studies no later than March 2013.
As for the 5 years, I found no explanation. Maybe they will chalk that up to lesson learned, just like when they decided not to oversee compounding pharmacies mixing steroids to be injected directly into patients’ spines…
For more info about the FDA announcement, click here.
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