Department of Pharmacy, Chi Mei Medical Center, Tinan, Taiwan.
Eur J Clin Pharmacol. 2009 Dec;65(12):1237-43. doi: 10.1007/s00228-009-0698-4.
To quantify the effect of exposures to digoxin–clarithromycin interactions on the risk of digoxin toxicity requiring hospitalizations in a population-based manner in a Taiwanese population.
This is a retrospective population-based nested case–control study. Data were retrieved from the National Health Insurance Research Database. Heart failure (HF) patients newly treated with digoxin between 1 January 2001 and 31 December 2004 were retrieved from the database as the study cohort. Case patients, admitted to the hospitals with the diagnosis of digoxin intoxication (ICD-9 code 972.1) were identified from the study cohort and compared with the matched controls for the receipt of clarithromycin.
A total of 154,058 patients were identified as the study cohort; from these, 595 cases and 27,020 matched controls were selected for study. The prescription of clarithromycin at 7, 14, and 30 days prior to the index date was associated with a 4.36- (95% CI 1.28–14.79), 5.07- (95% CI 2.36–10.89), and 2.98-fold (95% CI 1.59–5.63) increase in hospitalization for digoxin intoxication, respectively. The results of the dose–response relationship also indicated that clarithromycin prescribed with a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55.41-fold (95% CI 9.31–329.9) increase of the risk, which is significantly greater than that prescribed with a 1–2 PDD/DDD ratio (adjusted OR 4.81; 95% CI 1.88–12.30) or with a <1 PDD/DDD ratio (adjusted OR 0.78; 95% CI 0.19–3.20).
This study provides empirical evidence that digoxin–clarithromycin interactions do increase the risk of hospitalization for digoxin intoxication in HF patients and that this risk could reach as high as 55.4-fold. We strongly recommend that the combined use of digoxin with clarithromycin should be avoided and that digoxin concentrations should be monitored closely in situations where the combination can not be avoided.
以人群为基础，量化地高辛-克拉霉素相互作用暴露对台湾人群中地高辛中毒住院风险的影响。
这是一项回顾性基于人群的巢式病例对照研究。数据来自国家健康保险研究数据库。从数据库中检索 2001 年 1 月 1 日至 2004 年 12 月 31 日期间新接受地高辛治疗的心力衰竭（HF）患者作为研究队列。从研究队列中确定因地高辛中毒（ICD-9 代码 972.1）入院的病例患者，并与接受克拉霉素的匹配对照进行比较。
共确定 154058 名患者作为研究队列；从这些患者中，选择了 595 例病例和 27020 例匹配对照进行研究。在索引日期前 7、14 和 30 天内开具克拉霉素处方与住院治疗地高辛中毒的风险分别增加 4.36 倍（95%CI 1.28-14.79）、5.07 倍（95%CI 2.36-10.89）和 2.98 倍（95%CI 1.59-5.63）。剂量-反应关系的结果还表明，处方每日剂量（PDD）/定义每日剂量（DDD）比值>2 的克拉霉素与风险增加 55.41 倍（95%CI 9.31-329.9）相关，这明显大于 1-2 PDD/DDD 比值（调整后的 OR 4.81；95%CI 1.88-12.30）或<1 PDD/DDD 比值（调整后的 OR 0.78；95%CI 0.19-3.20）的比值。
本研究提供了经验证据，表明地高辛-克拉霉素相互作用确实会增加心力衰竭患者地高辛中毒住院的风险，并且这种风险可能高达 55.4 倍。我们强烈建议避免地高辛与克拉霉素联合使用，并在无法避免联合使用的情况下密切监测地高辛浓度。
