Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Ann Pharmacother. 2013 Nov;47(11):1420-8. doi: 10.1177/1060028013500940.
During the 2009 H1N1 influenza pandemic, the UK Medicines and Healthcare Products Regulatory Agency received case reports suggesting a potentiation of warfarin anticoagulation by the antiviral drug oseltamivir. We evaluated this putative interaction using Medicare data.
To determine the frequency of bleeding following addition of oseltamivir or comparator drugs among Medicare beneficiaries taking warfarin.
This was a retrospective cohort evaluation using Medicare nationwide data. Cohort members were Medicare Parts A, B, and D beneficiaries from June 30, 2006 to October 31, 2010 receiving warfarin for at least 1 month prior to a concomitant drug of interest (oseltamivir, ampicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and angiotensin-converting enzyme (ACE) inhibitors). Bleeding within 14 days of new prescriptions for oseltamivir or comparators was identified using inpatient or emergency department ICD-9 (International Classification of Diseases, ninth revision) discharge diagnosis codes for gastrointestinal hemorrhage, epistaxis, hematuria, and intracranial bleeding. Patients with bleeding within 30 days preceding the prescription concomitant to warfarin were excluded.
With concomitant ACE inhibitors as reference, adjusted odds ratios (ORs) for any bleeding events within 14 days were 1.47 (95% confidence interval [CI] = 1.08-1.88), 1.24 (95% CI = 0.97-1.57), and 2.74 (95% CI = 2.53-3.03), for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively. In a sensitivity analysis, adjusted ORs over a 7-day period were 1.89 (95% CI = 1.29-2.59), 1.47 (95% CI = 1.06-2.02), and 3.07 (95% CI = 2.76-3.49) for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively.
Bleeding with oseltamivir plus warfarin was not significantly increased over a 14-day observation period; a sensitivity analysis showed a statistically significant increase over a 7-day period; in contrast, the data consistently showed the known tendency of TMP-SMX to potentiate the effects of warfarin. The results should be interpreted with the limitations of this approach in mind, including the inability to control for unmeasured confounders.
在 2009 年 H1N1 流感大流行期间，英国药品和保健品管理局收到病例报告，提示抗病毒药物奥司他韦增强了华法林的抗凝作用。我们使用医疗保险数据评估了这种潜在的相互作用。
确定在接受华法林治疗的医疗保险受益人群中，加用奥司他韦或对照药物后出血的频率。
这是一项使用医疗保险全国范围数据的回顾性队列评估。队列成员为 2006 年 6 月 30 日至 2010 年 10 月 31 日接受至少 1 个月华法林治疗的医疗保险 A、B 和 D 部分受益人的合并药物（奥司他韦、氨苄西林、甲氧苄啶-磺胺甲恶唑（TMP-SMX）和血管紧张素转换酶（ACE）抑制剂）。使用住院或急诊 ICD-9（国际疾病分类，第 9 版）出院诊断代码识别奥司他韦或对照药物新处方后 14 天内的出血事件，用于胃肠道出血、鼻出血、血尿和颅内出血。排除在与华法林同时服用的处方前 30 天内有出血事件的患者。
以 ACE 抑制剂为参照，奥司他韦、氨苄西林、TMP-SMX 与华法林联合治疗后 14 天内任何出血事件的调整比值比（OR）分别为 1.47（95%置信区间[CI] = 1.08-1.88）、1.24（95% CI = 0.97-1.57）和 2.74（95% CI = 2.53-3.03）。在一项敏感性分析中，7 天内调整后的 OR 分别为 1.89（95% CI = 1.29-2.59）、1.47（95% CI = 1.06-2.02）和 3.07（95% CI = 2.76-3.49）。
在 14 天的观察期内，奥司他韦与华法林联合使用的出血风险并未显著增加；敏感性分析显示在 7 天内有统计学意义的增加；相反，数据一致显示 TMP-SMX 增加华法林效果的已知倾向。应该考虑到这种方法的局限性来解释结果，包括无法控制未测量的混杂因素。
