Department of Medicine, University of Toronto, Ont., Canada.
CMAJ. 2011 Feb 22;183(3):303-7. doi: 10.1503/cmaj.100702. Epub 2011 Jan 17.
The macrolide antibiotics clarithromycin and erythromycin may potentiate calcium-channel blockers by inhibiting cytochrome P450 isoenzyme 3A4. However, this potential drug interaction is widely underappreciated and its clinical consequences have not been well characterized. We explored the risk of hypotension or shock requiring hospital admission following the simultaneous use of calcium-channel blockers and macrolide antibiotics.
We conducted a population-based, nested, case-crossover study involving people aged 66 years and older who had been prescribed a calcium-channel blocker between Apr. 1, 1994, and Mar. 31, 2009. Of these patients, we included those who had been admitted to hospital for the treatment of hypotension or shock. For each antibiotic, we estimated the risk of hypotension or shock associated with the use of a calcium blocker using a pair-matched analytic approach to contrast each patient's exposure to each macrolide antibiotic (erythromycin, clarithromycin or azithromycin) in a seven-day risk interval immediately before admission to hospital and in a seven-day control interval one month earlier.
Of the 7100 patients admitted to hospital because of hypotension while receiving a calcium-channel blocker, 176 had been prescribed a macrolide antibiotic during either the risk or control intervals. Erythromycin (the strongest inhibitor of cytochrome P450 3A4) was most strongly associated with hypotension (odds ratio [OR] 5.8, 95% confidence interval [CI] 2.3-15.0), followed by clarithromycin (OR 3.7, 95% CI 2.3-6.1). Azithromycin, which does not inhibit cytochrome P450 3A4, was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8). We found similar results in a stratified analysis of patients who received only dihydropyridine calcium-channel blockers.
In older patients receiving a calcium-channel blocker, use of erythromycin or clarithromycin was associated with an increased risk of hypotension or shock requiring admission to hospital. Preferential use of azithromycin should be considered when a macrolide antibiotic is required for patients already receiving a calcium-channel blocker.
大环内酯类抗生素克拉霉素和红霉素可能通过抑制细胞色素 P450 同工酶 3A4 来增强钙通道阻滞剂。然而，这种潜在的药物相互作用被广泛低估，其临床后果尚未得到很好的描述。我们探讨了同时使用钙通道阻滞剂和大环内酯类抗生素后发生低血压或休克需要住院治疗的风险。
我们进行了一项基于人群的、嵌套的病例交叉研究，纳入了 1994 年 4 月 1 日至 2009 年 3 月 31 日期间接受钙通道阻滞剂治疗的年龄在 66 岁及以上的人群。在这些患者中，我们纳入了因低血压或休克住院治疗的患者。对于每种抗生素，我们使用配对分析方法估计与使用钙阻滞剂相关的低血压或休克风险，将每个患者在住院前 7 天的风险间隔内和一个月前的 7 天对照间隔内暴露于每种大环内酯类抗生素（红霉素、克拉霉素或阿奇霉素）进行对比。
在因低血压而接受钙通道阻滞剂治疗而住院的 7100 名患者中，有 176 名患者在风险间隔或对照间隔内接受了大环内酯类抗生素治疗。红霉素（最强的细胞色素 P450 3A4 抑制剂）与低血压的相关性最强（比值比 [OR] 5.8，95%置信区间 [CI] 2.3-15.0），其次是克拉霉素（OR 3.7，95% CI 2.3-6.1）。不抑制细胞色素 P450 3A4 的阿奇霉素与低血压风险增加无关（OR 1.5，95% CI 0.8-2.8）。我们在仅接受二氢吡啶类钙通道阻滞剂的患者的分层分析中也得到了类似的结果。
在接受钙通道阻滞剂治疗的老年患者中，使用红霉素或克拉霉素与低血压或休克需要住院治疗的风险增加相关。当需要大环内酯类抗生素治疗已经接受钙通道阻滞剂的患者时，应优先考虑使用阿奇霉素。
