Mahé Isabelle, Caulin Charles, Bergmann Jean-François
Service Médecine A, Hôpital Lariboisière, Paris, France.
Drug Saf. 2004;27(5):325-33. doi: 10.2165/00002018-200427050-00004.
Paracetamol (acetaminophen) is the analgesic and antipyretic therapy of choice for patients receiving oral anticoagulation. It is widely used by patients in both prescription and over-the-counter products, resulting in frequent co-prescription with oral anticoagulants, especially in elderly patients. Indeed, older patients are the most likely to receive this combination of drugs because indications for both oral anticoagulation and analgesic therapy increase with age. For many years reports have presented evidence both for and against the idea that paracetamol may potentiate the anticoagulant effect of oral anticoagulants, thus increasing haemorrhagic risk in patients receiving this combination of drugs. This issue has continued to be a matter of debate in recent publications. No clear practical conclusion can be drawn from the studies because of methodological bias and the lack of clinical relevance. No prospective, randomised study assessing the effect of paracetamol on the anticoagulant effect of oral anticoagulants as used in clinical practice (i.e. the types of patients and dosages used in clinical practice) are available in the literature. The implications are considerable since on the one hand, the ingestion of paracetamol may be a cause of altered anticoagulation in patients who regularly take oral anticoagulation and who may have a haemorrhagic risk factor; and on the other hand, paracetamol might be the analgesic drug of choice that can be used without the need for any restrictions in patients receiving oral anticoagulant drugs. A comprehensive search of Medline and EMBASE for studies and case reports from 1966-2002 was performed in order to review the available literature on the interaction between paracetamol and oral anticoagulant drugs. In conclusion, the potential interaction between oral anticoagulant drugs and paracetamol is an important unanswered question, due to the growing incidence of the concomitant use of these drugs and the possible bleeding implications. The association between paracetamol and the occurrence of excessive INR values remains controversial due to lack of prospective clinical studies assessing the effect of the prescription of paracetamol in patients receiving long-term oral anticoagulation in clinical conditions. Such a study is currently ongoing.
对乙酰氨基酚(醋氨酚)是接受口服抗凝治疗患者的首选止痛和解热药物。它在处方药和非处方药产品中都被患者广泛使用,导致其与口服抗凝剂经常联合处方,尤其是在老年患者中。事实上,老年患者最有可能接受这种药物组合,因为口服抗凝治疗和止痛治疗的适应症都随年龄增加。多年来,关于对乙酰氨基酚是否可能增强口服抗凝剂的抗凝作用从而增加接受这种药物组合治疗的患者出血风险的观点,有支持和反对的证据。在最近的出版物中,这个问题仍然是一个争论的焦点。由于方法学上的偏差和缺乏临床相关性,从这些研究中无法得出明确的实际结论。文献中没有前瞻性、随机研究评估在临床实践中使用的对乙酰氨基酚对口服抗凝剂抗凝作用的影响(即临床实践中使用的患者类型和剂量)。其影响相当大,因为一方面,对乙酰氨基酚的摄入可能是定期服用口服抗凝剂且可能有出血风险因素的患者抗凝改变的一个原因;另一方面,对乙酰氨基酚可能是在接受口服抗凝药物治疗的患者中无需任何限制即可使用的首选止痛药物。为了回顾关于对乙酰氨基酚与口服抗凝药物相互作用的现有文献,对1966年至2002年期间Medline和EMBASE上的研究和病例报告进行了全面检索。总之,由于这些药物联合使用的发生率不断增加以及可能的出血影响,口服抗凝药物与对乙酰氨基酚之间的潜在相互作用是一个重要的未解决问题。由于缺乏评估在临床情况下接受长期口服抗凝治疗的患者使用对乙酰氨基酚处方效果的前瞻性临床研究,对乙酰氨基酚与国际标准化比值(INR)过高之间的关联仍存在争议。这样一项研究目前正在进行中。