Medication for epileptic seizures, a positive move

Analysis of studies of two widely-used epilepsy drugs indicates that fosphenytoin provides effective, rapid treatment of life-threatening continuous seizures, with a lower risk of adverse effects.

The review of fosphenytoin in the treatment of the condition known as status epilepticus appears in the premier issue of the journal Core Evidence, the first international peer-reviewed publication to assess medications by critically evaluating evidence on clinical effectiveness and outcomes.

Status epilepticus, in which epileptic seizures occur continuously or in rapid succession, is a significant public health problem, with about 150,000 new cases in the United States each year and about 40,000 deaths annually; a mortality rate of about 22%. The condition requires swift emergency treatment, usually through administration of drugs intravenously.

Both phenytoin and fosphenytoin are among the drugs approved for this use by the U.S. Food and Drug Administration (FDA). However, rapid intravenous administration of phenytoin, required for quick termination of seizures, can lead to severe venous adverse effects.

“One of the most poorly understood and potentially serious local complications of intravenous phenytoin administration is the purple glove syndrome, which is characterized by progressive limb swelling, discoloration and pain,” said Andrew Thomson, PhD, who authored the review. “While it is clear that phenytoin is effective for treatment of status epilepticus, the way it is formulated limits how fast it can be infused and influences its tolerability,” Dr Thomson said.

Fosphenytoin, manufactured by Pfizer Inc. and marketed in the United States by Eisai Inc. under the trade name Cerebyx®, is a precursor of phenytoin and was developed to overcome the often severe venous adverse effects that can occur after giving phenytoin intravenously.

The Core Evidence review concludes that there is now evidence that use of intravenous fosphenytoin leads to rapid achievement of therapeutic blood levels, with fewer side effects compared with phenytoin. “Fosphenytoin is a valuable treatment option for the rapid treatment of SE [status epilepticus]; the risk of venous adverse events is lower than with phenytoin…” the review concluded.

The article noted that the higher acquisition cost of fosphenytoin compared with phenytoin is an issue. The article observed that, “Nevertheless there is evidence that when fosphenytoin is administered as recommended the incidence of adverse effects is lower than with phenytoin, thereby avoiding costly management and treatment of these events,…”

The review also noted, however, that although there are some patients for which fosphenytoin may be the preferred option, such children, the elderly and others with poor access to veins, “there is very limited evidence to confirm this benefit.”