According to editorial, the US FDA has listened to complaints from patients and clinicians and recently sponsored 3 large clinical-pharmacological studies of patients with epilepsy to assess bioequivalence approval standards. The studies addressed several major concerns:
(1) Do single-dose ‘Abbreviated New Drug Application’ bioequivalence studies in healthy volunteers accurately predict absorption of generic antiepileptic drug (AED) formulations in patients with epilepsy?
(2) Do brand-name formulations and various generic AEDs provide comparable steady state concentrations during long-term dosing, particularly when patients are switched between disparate generic drugs?
(3) Are some patients with unstable epilepsy experiencing a formulation effect, with differing absorption of generic and reference-listed products, or does this effect simply represent an expected clinical variability among patients?
The editorial notes that this current study addresses the first issue. The second study evaluated bioequivalence during long-term dosing with Lamictal and 2 generic lamotrigine formulations and found that the steady state concentrations for the generic and brand name formulations were nearly identical. The third study showed that patients with brittle epilepsy had similar lamotrigine concentrations during long-term dosing with a generic lamotrigine formulation and Lamictal. In addition, seizures or adverse drug effects were the same with generic and brand name treatments.
The editorial concludes overall that “these 3 clinical pharmacokinetic studies are reassuring because they show that generic formulations approved for use by study volunteers provided similar drug delivery in patients with epilepsy during single and long-term dosing. These 3 studies also suggest that most patients with epilepsy can safely be treated with inexpensive generic lamotrigine formulation rather than the brand name formulation.” It acknowledges however that the studies do not explain common patient complaints of clinical problems after generic switches. It points out that two of the studies suggest clinical problems may mean some patients may be having negative placebo responses or may represent fluctuations in individual absorption and tolerability. It adds that the studies may also underestimate the number of patients who may have larger drug fluctuations and clinical problems. It highlights that the American Epilepsy Society recently endorsed the FDA-sponsored study findings, advised clinicians to counsel patients on the use of generic formulations to ensure that they are not surprised by cosmetic changes in tablets, and ensure that patients receive stable treatment with either immediate-release or modified-release formulations.