Department of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
J Clin Pharmacol. 2010 Jun;50(6):693-8. doi: 10.1177/0091270009351885. Epub 2010 Jan 15.
Amiodarone inhibits the metabolism of warfarin. Previous studies characterizing this drug interaction have focused on the effect of adding amiodarone to stable doses of warfarin. The objective of this study was to assess whether simultaneous initiation of warfarin and amiodarone results in early alteration of the international normalized ratio (INR) response to warfarin. Patients initiated on warfarin and amiodarone during the same hospitalization were included in the amiodarone (AMIO) group. Patients initiated on warfarin alone (n = 42) were identified for the CONTROL group. The AMIO and CONTROL groups were matched based on age, gender, and ejection fraction <40% using propensity score matching (final n = 18 patients per group). Total and average daily warfarin dose was lower in the AMIO group, yet INR values were similar on each day between the 2 groups. More patients in the AMIO group had an INR greater than 2 during the 5-day observation period as compared to the CONTROL group. In addition, there were trends toward greater deviation from INR values expected with a 5-mg daily warfarin dose among AMIO group patients. Simultaneous initiation of warfarin and amiodarone leads to an enhanced pharmacodynamic response to warfarin early in therapy. Although these data should be viewed as hypothesis generating, cautious dosing and monitoring with simultaneous initiation of warfarin and amiodarone may be warranted.
胺碘酮抑制华法林的代谢。之前研究药物相互作用的特征主要集中在添加胺碘酮对稳定剂量华法林的影响。本研究的目的是评估同时开始使用华法林和胺碘酮是否会导致华法林的国际标准化比值（INR）反应早期改变。在同一住院期间开始使用华法林和胺碘酮的患者被纳入胺碘酮（AMIO）组。单独开始使用华法林的患者（n=42）被纳入对照组（CONTROL）。使用倾向评分匹配（最终每组 18 例患者），根据年龄、性别和射血分数<40%对 AMIO 组和 CONTROL 组进行匹配。AMIO 组的总剂量和平均日剂量较低，但两组之间的 INR 值在每天都相似。与 CONTROL 组相比，AMIO 组在 5 天观察期内有更多的患者 INR 大于 2。此外，AMIO 组患者的 INR 值与每天 5 毫克华法林剂量的预期值之间存在更大的偏差趋势。华法林和胺碘酮同时开始使用会导致治疗早期对华法林的药效学反应增强。尽管这些数据应被视为假设产生，但同时开始使用华法林和胺碘酮时，谨慎的剂量和监测可能是必要的。
