{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:27:32Z","timestamp":1769747252903,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute zoster\u2010associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster\u2010associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster\u2010associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double\u2010blind, placebo\u2010controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster\u2010associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18\u2009mg\/kg (high dose), a single intravenous dose of fosphenytoin at 12\u2009mg\/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120\u2009min after dosing. Seventeen patients were randomly assigned to the low\u2010dose fosphenytoin group (<jats:italic>n<\/jats:italic>\u2009=\u20096, median age 62.5\u2009years, range 39\u201375\u2009years), high\u2010dose fosphenytoin group (<jats:italic>n<\/jats:italic>\u2009=\u20095, median age 69.0\u2009years, range 22\u201375\u2009years), and placebo group (<jats:italic>n<\/jats:italic>\u2009=\u20095, median age 52.0\u2009years, range 38\u201372\u2009years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high\u2010 and low\u2010dose fosphenytoin groups than in the placebo group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001 and <jats:italic>P<\/jats:italic>\u2009=\u20090.016, respectively). Responsiveness to intravenous fosphenytoin (\u22652\u2010point reduction in the numerical rating scale score from baseline to 120\u2009min after dosing) was inferred at plasma total phenytoin concentrations of 10\u201315\u2009\u03bcg\/mL. Treatment\u2010emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster\u2010associated pain.<\/jats:p><jats:p>Trial Registration: ClinicalTrials.gov NCT04139330.<\/jats:p>","DOI":"10.1111\/1346-8138.17054","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T09:35:28Z","timestamp":1703669728000},"page":"234-242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster\u2010associated pain: A placebo\u2010controlled randomized trial"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-1900","authenticated-orcid":false,"given":"Masako","family":"Iseki","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Juntendo University Faculty of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-7033","authenticated-orcid":false,"given":"Takenobu","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kawasaki Medical School General Medical Center  Okayama Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-888X","authenticated-orcid":false,"given":"Youichi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine University of Yamanashi  Chuo Yamanashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Majima","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shizuoka City Shizuoka Hospital  Shizuoka Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Pain Clinic NTT Medical Center Tokyo  Shinagawa Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-3993","authenticated-orcid":false,"given":"Daisuke","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Dermatology Aichi Medical University School of Medicine  Nagakute Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumimasa","family":"Amaya","sequence":"additional","affiliation":[{"name":"Department of Pain Management and Palliative Care Medicine Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-8427","authenticated-orcid":false,"given":"Toshio","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology Juntendo University Shizuoka Hospital  Izunokuni Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Inafuku","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kimitsu Chuo Hospital  Kisarazu Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshifumi","family":"Kosugi","sequence":"additional","affiliation":[{"name":"Department of Palliative Care Saga\u2010Ken Medical Centre Koseikan  Saga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Dermatology KKR Sapporo Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-5756","authenticated-orcid":false,"given":"Tokiko","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Division of Dermatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-5707","authenticated-orcid":false,"given":"Toshihisa","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Dermatology Takamatsu Red Cross Hospital  Takamatsu Kagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Nobelpharma Co., Ltd.  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