title: Does paracetamol potentiate the effects of oral anticoagulants?: a literature review.
abstract: 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.
authors.affiliation: Service Médecine A, Hôpital Lariboisière, Paris, France. isabelle.mahe@lrb.ap-hop-paris.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mahé
authors.forename: Charles
authors.initials: C
authors.lastname: Caulin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bergmann
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000494:pharmacology*; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male
chemical_list: D018712:Analgesics, Non-Narcotic; D000925:Anticoagulants; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System