Phenytoin revisited

Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. It has been the subject of more than 8,000 published papers, which include clinical reports of its usefulness in approximately 100 diseases and symptoms. In the United States the only indications for use in the official labeling for phenytoin are various types of seizures. An advisory committee of the Food and Drug Administration recently recommended the addition of certain cardiac arrhythmias to the labeling. To determine whether other uses should be added to the labeling and whether additional clinical trials should be encouraged, an in-depth review of the published literature was undertaken. This review revealed that, on the basis of controlled studies, phenytoin is probably useful in the continuous muscle fiber activity syndrome, myotonic muscular dystrophy, and myotonia congenita. In addition, phenytoin appears to be potentially useful in recessive dystrophic epidermolysis bullosa, intermittent explosive disorder, anxiety disorder in which anger and irritability are prominent features, and, topically, in burns and refractory skin ulcers. Additional clinical studies are needed before definitive conclusions can be drawn. Clinical trials of phenytoin in most of these disorders are ongoing or are contemplated. Any labeling changes will await results of the studies. Based on phenytoin's pharmacologic effects in animals, controlled trials of the drug appear to be warranted in cerebral ischemia and stroke, spinal cord injury, angina pectoris, and fractures in which the rate of healing is poor.