Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: Recommendations to minimize the functional consequences

Abstract

Objective. To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.Methods. We performed a crossover, open-label study in 9 healthy volunteers. They received for 6 days 3 different treatments separated by 14 days of washout: 1) naproxen 2 hours before aspirin, 2) aspirin 2 hours before naproxen, and 3) aspirin alone. The primary end point was the assessment of serum thromboxane B 2 (TXB 2 ) 24 hours after the administration of naproxen 2 hours before aspirin on day 6 of treatment. In 5 volunteers, the rate of recovery of TXB 2 generation (up to 72 hours after drug discontinuation) was assessed in serum and in platelet-rich plasma stimulated with arachidonic acid (AA) or collagen. Conclusion. Sequential administration of 220 mg naproxen twice a day and low-dose aspirin interferes with the irreversible inhibition of platelet cyclooxygenase 1 afforded by aspirin. The interaction was smaller when giving naproxen 2 hours after aspirin. The clinical consequences of these 2 schedules of administration of aspirin with naproxen remain to be studied in randomized clinical trials. Results. Twenty-four hoursArthritis in general and osteoarthritis in particular are increasingly becoming global problems; however, at this time, there is no known cure for osteoarthritis. Most forms of treatment therefore have dealt with the alleviation and management of chronic pain, which can affect normal functioning and quality of life of patients.

Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

“…The drug-drug pharmacodynamic interaction has been characterized biochemically and in clinical studies designed to distinguish between a predominantly irreversible inhibition by aspirin and a predominately reversible inhibition by the NSAID (9-18). However, the deconvolution of reversible and irreversible antiplatelet effects can be challenging-particularly with drugs with variable and extended half-lives, such as naproxen (13,14,(16)(17)(18). We hypothesized that direct measurement of COX-1 acetylation by MS using a proteomics approach (25) would enable a quantitative analysis of the propensity of chemically distinct NSAIDs to cause the drug-drug interaction in vivo.…”

“…Experiments with radio-labeled aspirin in vitro and X-ray crystallography suggested that some but not all NSAIDs may compete with aspirin for binding COX-1 (9,10). This concept was borne out further in clinical studies that exploited the distinct recovery kinetics of platelet function between reversible COX inhibitors and the irreversible inhibitor aspirin to predict whether a drug-drug interaction might occur (11)(12)(13)(14)(15)(16)(17)(18). Again, heterogeneity was observed between studies, NSAIDs, doses, and time of dosing.…”

Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations.Diclofenac is not more dangerous

“…Irodalmi adatok alapján a két gyógyszercsoport együttes adásakor az ASA hatásának csökkenésére lehet számí-tani, így az atherothromboticus események kockáza-tának növekedése várható [8,9]. Az acetilszalicilsavval történő farmakodinámiás interferencia mértéke azonban az egyes NSAID-készítményeket összehasonlítva különböző mértékű.…”

Antithrombotic Drugs: Pharmacology and Implications for Dental Practice

“…5,6 Consideration regarding this issue may eventually prove moot because actual clinical relevance has been challenged impressively. Cryer et al 7 found thromboxane inhibition by aspirin to be reduced only 1% after 10 days of concurrent ibuprofen use, and Patel and Goldberg 8 found no increase in incidence of myocardial infarction over a 10-year period in patients with coronary disease taking ibuprofen with low-dose aspirin.…”

“…By this time the antiplatelet influence of aspirin will have been established. 6,9 Although low-dose aspirin does not introduce a major risk for bleeding following minor dental surgery, extensive surgery may require some consideration. This may be of even greater concern for patients medicated with thienopyridines such as clopidogrel (Plavix), but it is noteworthy that it was found insignificant following peripheral vascular surgery.…”