People with epilepsy, and their doctors, should be cautious when switching from brand-name phenytoin (Dilantin) to generic versions, researchers in Minnesota say.

They found that blood levels of the drug do not always reach therapeutic levels when the generic preparation is used, according to a report in the medical journal Neurology.

Dr. Ilo E. Leppik, at the University of Minnesota, Minneapolis, and colleagues observed that patients began to experience breakthrough seizures when their medication was switched from Dilantin Kapseals (Parke-Davis) to Mylan extended PHT sodium capsules (Mylan Pharmaceuticals, Inc.).

The U.S. Food and Drug Administration had approved the generic version in 1998 after clinical trials in healthy volunteers showed that the two preparations were biologically equivalent.

However, clinical studies do not always reflect clinical practice, the authors point out. They found that over a five-month period, 11 patients experienced increased seizures requiring hospitalization, emergency room visits or urgent clinic visits.

Leppik’s group notes that the state of Minnesota had mandated that patients in its health plan be treated with generics when available.

The researchers reviewed the records of eight patients who had blood levels of phenytoin measured while taking Dilantin, when they had been switched to the Mylan product, and after they went back on Dilantin. There was about a 30 percent decrease in levels of phenytoin during generic treatment, even though the prescribed doses were equivalent.

Leppik’s group notes that “the Mylan product and Dilantin are bioequivalent under fasting, but not fed, conditions.”

When these data were presented to the Minnesota Department of Health, the automatic substitution rule for phenytoin was reversed.

SOURCE: Neurology, October 26, 2004.