ジスロマックで血管死増加

昔（昭和50年頃）、ナウゼリン注射薬で死亡例が相次ぎ、昭和53年に発売中止になりました。

ナウゼリンの死亡原因は、アナフィラキシーでは無く、Torsades de pointes という致死的不整脈が原因であるということでした。

このTorsades de pointesは、ナウゼリン以外でも14員環系マクロライドでも起きることが報告されています。

QT延長を起こす薬剤ののリストでは重要視されていなかったので、あまり危険だと思っていなかったのですが、AZMも心血管死リスクを上げるようです。

特に胃腸炎で脱水があるときは要注意です。

ペニシリン系やセフェム系では2～3倍量投与が安全且つ有効な投与法として確立されていますが、個人的にはマクロライドの倍量投与は危険なのではないかと思っています。

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文献：Ray WA et al.Azithromycin and the Risk of Cardiovascular Death.N Engl J Med 2012; 366:1881-1890.

　テネシー州メディケイドコホートを対象に、アジスロマイシンと心血管死の関連調査。アジスロマイシン使用者は抗菌薬非使用に比べ心血管死リスク、全死因死亡リスクが増加した（ハザード比2.88、1.85）。アモキシリン使用者と比べても心血管死リスク、全死因死亡リスク増加と関連していた（同2.49、2.02）。

Azithromycin and the Risk of Cardiovascular Death

Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall, B.S., Patrick G. Arbogast, Ph.D., and C. Michael Stein, M.B., Ch.B.

N Engl J Med 2012; 366:1881-1890 May 17, 2012

Background

Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.

Methods

We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score–matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).

Results

During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.

Conclusions

During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.)