手足が震える病気というと、一般の方は Parkinson病を思い浮かべるかもしれません。他にも、本態性振戦や甲状腺機能亢進症といった病気が知られています。

しかし、意外と見落とされやすく、忘れてはいけないのが薬剤性です。食思不振などで時折処方されるスルピリド (ドグマチール) や、喘息で処方される β刺激薬など、比較的よく見かけます。

International Journal of Infectious Diseaseという雑誌の 2012年8月号に、抗菌薬 バンコマイシンで、重篤な振戦が出現した症例が掲載されていました。

Severe tremor due to vancomycin therapy: a case report and literature review

Vancomycin is a popular antimicrobial used to treat a variety of Gram-positive infections. Its side effect profile has been well defined due to its high global utilization as a result of the emergence of antimicrobial-resistant organisms in recent decades. Despite its widespread use, however, various idiosyncratic reactions may occur without adequate or universal reporting. We present a case of severe tremor due to vancomycin that has not been previously reported in the literature. Our patient might have been prone to this adverse effect given an underlying essential tremor. Causality is presumed based on the temporal association, while the pathophysiological link remains elusive.

この患者さんは、ベースに本態性振戦があったようです。バンコマイシン点滴で心内膜炎/膿瘍を治療していたところ、2週間くらいして急に全身に激しい振戦を発症しました。その際、リファンピシン、セフトリアキソンが併用されており、バンコマイシン血中濃度は治療域でした。バンコマイシンを中止し、30分ほどで振戦はよくなりました。その後もバンコマイシンを継続しましたが、2回とも同様のイベントが起こりました。

ジフェンヒドラミンを前投薬とし、症状に対してロラゼパムを用いてみましたが、無効でした。イベント 3回とも、バンコマイシンを中止すると症状は改善しました。バンコマイシンをダプトマイシンに変えると、このようなイベントはなくなりました。

考察では、最初にバンコマイシンの副作用がまとめられています。

Common reactions due to vancomycin include ‘red man syndrome’ (an erythematous rash on the face and upper body with or without associated hypotension; a result of histamine release due to rapid drug administration), eosinophilia, reversible neutropenia, and phlebitis. Less common reactions include DRESS syndrome (drug rash with eosinophilia and systemic symptoms), drug fever, Stevens–Johnson syndrome, thrombocytopenia, and vasculitis. Vancomycin-associated nephrotoxicity appears to be dose-related, with increased incidence occurring with high trough levels,² or when combined with other nephrotoxic agents (e.g., aminoglycosides).

そして、バンコマイシンが原因と推測される振戦について、過去の知見をまとめています。何故振戦がみられるのか、機序については不明とされています。

A subsequent search of the Health Canada adverse events database (Canada Vigilance Summary of Reported Adverse Reactions) searched September 1, 2011, yielded six cases of tremor potentially related to vancomycin therapy. The Summary is a spontaneous voluntary reporting system aimed at detecting signals of potential health product safety issues during the post-market period. Of the six cases identified, the median patient age was 73 years, 67% were female, 33% were documented as serious reactions, and all but one case suspected vancomycin as the sole drug responsible for the adverse event. Associated symptoms included chills, pyrexia, rash, flushing, vomiting, dizziness, and abdominal pain. Doses ranged from 0.5 to 2g every 6–24h, and the duration of therapy ranged from 1 to 14 days. Data on prevalence of renal dysfunction/failure and trough levels were not available.

A similar search of the Federal Drug Administration (FDA) Adverse Drug Events Database (AERS/Medwatch) from 1997 to 2011 yielded a total of 34 reports of tremor in which vancomycin was the primary suspect drug. Thirty-one (91%) cases were in adults, of which 26 (76%) were male. The highest incidence (26%) was observed in those aged 80–89 years. Seventeen (50%) patients required hospitalization, and five (15%) cases were considered to be life-threatening. The most common associated symptoms included chills, pyrexia, dyspnea, and rigors.

また、バンコマイシン同様 MRSAまでカバーするスペクトラムを持つ抗菌薬テイコプラニンでも、軽いものの振戦が出現した報告があるそうです。

One case of tremor was reported in an open efficacy and safety study of teicoplanin – a related glycopeptide.⁵ Although the tremor was described as mild, therapy was discontinued.

バンコマイシンは、MRSAをカバーしないといけないシチュエーションなどでしばしば使用される抗菌薬ですから、診療科にかかわらず、このような副作用情報は知っておいた方が良いと思います。

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