FDA Says There is No Scientific Evidence of Problems in Switching Bioequivalent Anti-epileptic Meds, But Further Study is Warranted

By Kurt R. Karst –      

Last month FDA responded to an August 25, 2010 request from New Jersey State Senator Joseph F. Vitale (D) concerning pending legislation – Assembly Bill 1995 (the State Senate version of which is Senate Bill 961) – that, if enacted, would require pharmacists to dispense epilepsy drugs from the same manufacturer as previously dispensed for certain patients, unless otherwise prescribed.  Although FDA’s response does not provide the Agency’s position on Assembly Bill 1995 as Sen. Vitale requested, it does provide some insight into FDA’s current thinking on the substitution of bioequivalent generic anti-epileptic drugs for their brand-name counterparts. 

The issue of generic anti-epileptic drug substitution has been brewing for a few years.  Questions have been raised about whether there is an increased risk of so-called “breakthrough” seizures or toxic side effects when patients are switched from a brand name anti-epileptic to a generic version.  Still pending at FDA is a 2006 citizen petition requesting that the Agency address the issue of brand-name and generic anti-epileptic drug substitution. 

In its response to Sen. Vitale, FDA comments that “[t]o date, we have not seen any scientific evidence that demonstrates a problem with therapeutic equivalence for this group of products or any other class of generic drug products.  Those who are questioning the quality of generic epilepsy products have produced only anecdotal evidence.”  Nevertheless, FDA further states:

[W]e believe that the concerns of some of those raising questions (in particular, physician groups) can not be dismissed lightly.  Because of FDA’s respect for these groups and the concern that patients may lose confidence in their prescribed medications, we have sought to conduct further study.  Our decision to further study this issue does not stem from doubt within the agency about data we currently have on approved generic epilepsy products.  Rather, it is based on a desire to obtain further independent scientific evidence that might address these concerns.

As we previously reported, last year Congress requested in the Conference Report (Report No. 111-279) accompanying the 2010 Agriculture, Rural Development, FDA, and Related Agencies Appropriations Act (Public Law No. 111-80) that FDA examine and report on “A” rated anti-epileptic drugs (i.e., drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products).  According to the Conference Report:

The conferees request the FDA report on adverse events and seizures associated with brand and generic anti-epileptic drugs.  Specifically, the agency should examine the pharmacokinetic profiles of “A” rated anti-epileptic drugs from different manufacturers of the same therapeutic agent.  The Committee directs the FDA to submit a report not later than September 30, 2010, detailing whether the agency believes that any changes to the current bioequivalence testing should be recommended.

Your intrepid bloggers understand that FDA did not submit the report by the September 30, 2010 deadline and that the Agency is still working on the report.  It is unclear when the report might be completed and submitted to Congress.  Nevertheless, FDA’s response to Sen. Vitale seems to give some foreshadowing as to what conclusions the Agency may include in its report.