IV fosphenytoin appears to be a promising alternative treatment for acute zoster-associated pain: Study

The researchers revealed a rapid analgesic effect of a single dose of IV fosphenytoin for acute ZAP in patients with HZ for whom nonopioid drugs had shown an insufficient analgesic effect. "Therefore, IV fosphenytoin is promising as a potential alternative treatment for acute ZAP," they wrote.

Herpes zoster (HZ) is a common viral disease caused by reactivation of the varicella-zoster virus, which lies latent in the dorsal root ganglia of the cranial and spinal nerves after primary varicella-zoster virus infection. Most patients with herpes zoster develop acute zoster-associated pain. Nonopioid analgesics are usually used for treating acute ZAP but are frequently ineffective.

Masako Iseki, Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan, and colleagues administered IV fosphenytoin, the prodrug of phenytoin, to patients with acute ZAP to investigate its analgesic safety and efficacy.

They conducted a phase II, double-blind, placebo-controlled, randomized trial at 13 medical institutions in Japan of IV fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect.

The patients were randomly assigned in a 1:1:1 ratio to receive a single IV dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or a placebo.

The study's primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min following the dosing.

The study led to the following findings:

• Seventeen patients were assigned randomly to the low-dose fosphenytoin group (n = 6, median age 62.5 years), high-dose fosphenytoin group (n = 5, median age 69.0 years), and placebo group (n = 5, median age 52.0 years). One patient was excluded because of investigational drug dilution failure.
• This study was discontinued due to the influences of coronavirus disease 2019.
• The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group.
• Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10–15 μg/mL.
• Treatment-emergent adverse events caused no safety concerns in the clinical setting, and intravenous fosphenytoin was well tolerated.

"Intravenous fosphenytoin appears to be a promising and effective alternative treatment for acute zoster-associated pain," the researchers wrote. "A further confirmatory clinical study is required."

Reference:

Iseki, M., Yamamoto, T., Ogawa, Y., Majima, Y., Abe, Y., Watanabe, D., Amaya, F., Hasegawa, T., Inafuku, K., Kosugi, T., Nomura, Y., Deguchi, T., Hamada, T., Shimizu, K., Arai, S., Takahashi, M., Hamada, I., Ishikawa, Y., & Kawashima, M. (2024). Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster-associated pain: A placebo-controlled randomized trial. The Journal of Dermatology, 51(2), 234-242. https://doi.org/10.1111/1346-8138.17054