Adverse Effects of Phenytoin on Peripheral Nerves and Neuromuscular Junction: A Review

Abstract

Review of the literature shows that long-term phenytoin therapy is associated with peripheral neuropathy and neuromuscular disorder that rarely can be symptomatic. The usual manifestations of the peripheral neuropathy are lower extremity areflexia, sensory deficits, and reduced conduction velocities. The risk for these peripheral nerve abnormalities is greater with increased serum levels or long duration of therapy (usually more than 5 years). The relative risks according to age groups or number and kinds of antiepileptic drugs used are undetermined. It is not known if detected abnormalities are static or slowly progressive. Isolated case reports have claimed the resolution of signs and symptoms after discontinuance of therapy or correction of a state of intoxication. Appropriate measures to prevent the appearance or progression of the complications are discussed in light of the available evidence.

Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new‐onset epilepsy: A randomized double‐blind clinical trial

“…In addition to the tolerability issues associated with the use of PHT observed in this and other studies (rash, CNS side effects, nausea), long‐term use of PHT may be associated with peripheral neuropathy (including absent patellar or Achilles reflex, decreased conduction velocity, and sensory impairment) and impaired neuromuscular transmission (increased neuromuscular fatigability following repetitive stimulation) (So & Penry, 1981), gingival hyperplasia, coarsening of the facial features, and hirsutism (Trevisol‐Bittencourt et al., 1999). Patients with new‐onset epilepsy are often prescribed PHT as initial treatment in the emergency department (Huff et al., 2001), and it is common practice for this treatment to continue when patients consult a neurologist (Ortho‐McNeil Neurology Consultant Surveys, 2003–2004) despite the possibility of these long‐term safety concerns.…”

Clinical and Electrophysiologic Evaluation of Peripheral Nerve Function in Chronic Phenytoin Therapy

“…It is generally accepted that chronic anticonvulsant therapy, and in particular, chronic phenytoin intake, results in clinical and electrophysiologic abnormalities of the peripheral nerves (Reynolds, 1975;So and Penry, 1981). However, most investigations have failed to consider factors that are thought to be of importance in the development of peripheral nerve abnormalities.…”

Topical Phenytoin in Neuralgic Pain, Peripheral Modulation of Central Sensitization: Two Case Reports

“…Effects of phenytoin on peripheral nervous system read-outs have been described since nearly half a century, based on a number of different studies and models [56][57][58][59]. Treatment in sciatic nerve rat and frog models with phenytoin, even at subclinical concentrations of 5 mg/ml, caused a significant decrement in the amplitude and increment in the latency of the compound action potential [1,60].…”