Phenytoin – Safety Considerations and Administration Guidelines

Severe Cutaneous Reactions

Patients carrying the HLA‑B*15:02 allele have a markedly increased risk of Stevens‑Johnson syndrome and toxic epidermal necrolysis when treated with phenytoin. 1

Intravenous phenytoin can cause “purple‑glove” syndrome, local tissue necrosis, and phlebitis, especially when administered rapidly or without proper dilution. Reported cases involve multiple sources. [1][2]3

Rapid intravenous infusion of phenytoin may produce hypotension, bradyarrhythmias, impaired myocardial contractility, dysrhythmias, and even cardiac arrest. These events have been documented in both pediatric and adult populations. [1][2][4][5]

Dilution: Phenytoin must be diluted in normal saline; it is incompatible with glucose‑containing solutions. [4][5]
Infusion rate limits: Do not exceed 1 mg·kg⁻¹·min⁻¹ in children or 50 mg·min⁻¹ in adults to reduce cardiovascular and tissue‑injury risk. [4][5]6
Monitoring: Continuous heart‑rate monitoring is required; the infusion rate should be reduced if the heart rate falls by ≥10 beats·min⁻¹. [4][5]
Alternative formulation: Fosphenytoin is preferred over phenytoin when available because it carries a lower risk of adverse cardiac effects and local tissue complications. [1][2][3][4]5

Neonates: Due to reduced plasma protein binding, neonates are at higher risk of phenytoin toxicity; phenobarbital is recommended as the first‑line antiepileptic in this age group. [4][5]