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Effects of oxametacin on coumarin anticoagulation and on platelet function in humans
Insights
Oxametacin (Flogar) potentiates anticoagulant effects in patients taking warfarin, necessitating dose adjustments. It did not significantly inhibit platelet aggregation in healthy volunteers.
Area of Science:
- Pharmacology
- Clinical Medicine
- Drug Interactions
Background:
- Anticoagulant therapy is crucial for preventing thromboembolic events.
- Non-steroidal anti-inflammatory drugs (NSAIDs) can affect hemostasis.
- Oxametacin is an NSAID with potential effects on coagulation.
Purpose of the Study:
- To evaluate the interaction between oxametacin and warfarin in anticoagulated patients.
- To assess the ex vivo antiplatelet effects of oxametacin compared to aspirin and indomethacin.
Main Methods:
- 12 chronically anticoagulated patients received oxametacin (100 mg TID).
- Thrombotest, prothrombin time, and activated partial thromboplastin time were monitored.
- Ex vivo platelet aggregation and 5-HT release were measured in volunteers after drug administration.
Main Results:
- Oxametacin significantly decreased Thrombotest percentages and prolonged clotting times.
- One-third of patients required warfarin dose adjustments.
- Oxametacin did not exhibit a clear-cut inhibitory effect on platelet aggregation.
Conclusions:
- Oxametacin potentiates the effects of warfarin, requiring careful monitoring and potential dose adjustments in anticoagulated patients.
- Oxametacin lacks significant ex vivo antiplatelet activity comparable to aspirin.
Abstract:
In 12 chronically anticoagulated patients the administration of 1-p-chlorobenzoyl-5-methoxy-2-methyl-3-indoacetohydroxamic acid (oxametacin, Flogar), three times 100 mg a day, decreased the thrombotest percentage from a mean of 11.2% to a mean of 8.3% after one week and of 7.8% after two weeks of treatment. A potentiating effect of oxametacin was also found when the prothrombin time or the activated partial thromboplastin time were used as parameters. In one third of our patients an adaptation of the coumarin dose or even an interruption in the warfarin administration was necessary. Although no severe bleedings occurred, care should be taken in prescribing oxametacin to anticoagulated patients. In a second part of this study we compared the ex vivo effects of a single oral dose of 1 g of acetylsalicylic acid, 50 mg of indometacin and 100 mg of oxametacin in human volunteers. Platelet aggregation and 5HT--14C release induced by collagen. Thrombofax, ADP, adrenaline (epinephrine), bovine plasma and ristocetin were measured before, 1 and 24 h after drug administration. A clear-cut inhibitory effect as induced by acetylsalicylic acid was not found for oxametacin.