mobic and Hemorrhage

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1), thereby inhibiting platelet function via blockade of thromboxane A2 (TxA2) formation, and COX-2, the enzyme that mediates inflammatory responses. Meloxicam is a relatively COX-2-selective anti-arthritis drug that shows significant TxA2 inhibition, albeit less than traditional NSAIDs. A randomized, double-blind, placebo-controlled trial was conducted in 79 healthy adults to compare the effects of once-daily therapeutic (7.5 mg, 15 mg) and supratherapeutic (30 mg) doses of meloxicam with extended-release indomethacin (Indo-ER 75 mg once daily) on bleeding time, TxA2 formation, and platelet aggregation. The authors measured platelet aggregation to COX-1-dependent (ADP arachidonate) and COX-1-independent (high-dose collagen) agonists, bleeding time, serum TxB2, and clotting times (aPTT and PT) after 8 days' administration and at 3 and 6 hours after steady-state dosing. Meloxicam significantly decreased TxB2 production compared with placebo in a dose-dependent fashion, reaching a peak of 77% inhibition 6 hours after 30 mg meloxicam; Indo-ER blocked TxB2 formation by 96% at the same time point. However, neither acute nor 8 days' administration of meloxicam at any dose caused a significant increase in bleeding time or inhibition of platelet aggregation to any agonist when compared with placebo. By contrast, Indo-ER significantly increased the bleeding time and inhibited platelet aggregation to COX-1-dependent agonists 6 hours after dosing. Clotting times were unaffected by any drug. It was concluded that unlike nonselective NSAIDs, meloxicam's blockade of TxA2 formation (even at supratherapeutic doses) does not reach levels that result in decreased in vivo platelet function, as measured by bleeding time and aggregometry. In this study of healthy subjects, meloxicam did not interfere with platelet-mediated hemostasis.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Bleeding Time; Blood Coagulation; Blood Platelets; Double-Blind Method; Female; Hemorrhage; Humans; Indomethacin; Male; Meloxicam; Middle Aged; Partial Thromboplastin Time; Platelet Aggregation; Platelet Count; Prothrombin Time; Thiazines; Thiazoles; Thromboxane B2

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.

Topics: Adenosine Diphosphate; Administration, Intravenous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Specimen Collection; Collagen; Cyclooxygenase Inhibitors; Drug Compounding; Epinephrine; Female; Healthy Volunteers; Hemorrhage; Humans; Ketorolac; Male; Meloxicam; Nanoparticles; Pain; Platelet Aggregation; Platelet Function Tests; Reagent Kits, Diagnostic

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase > or =15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of > or =15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Drug Interactions; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Meloxicam; Middle Aged; Retrospective Studies; Risk Factors; Thiazines; Thiazoles; Warfarin

The purpose of this study was to investigate the effects of ellagic acid on platelet expression via the cyclooxygenase (COX) pathway by examining its effects on platelet activation and comparing them with known COX inhibitors in male Sprague-Dawley rats. Ellagic acid is a major compound found in certain fruits and nuts. It has been attributed as having anti-inflammatory, free radical scavenging, and coagulation properties as well as effects on tumor genesis in multiple forms of cancer. We assessed the similarities of ellagic acid to known COX-2 specific and nonspecific COX inhibitors by examining their effects on platelet activation via use of P-selectin flow cytometry. Compared with the vehicle group, both the ellagic acid (P = .035) and the ketorolac (P = .038) groups demonstrated a significant decrease in platelet activation (P = .026). Furthermore, compared with all other groups, ellagic acid plus ketorolac group showed a significant decrease in platelet activation (P = .01). Our findings suggest that ellagic acid is likely a nonspecific COX inhibitor. It also suggests that combining ellagic acid with a known nonspecific COX inhibitor such as ketorolac may cause a significant decrease in platelet activity and an increase in blood loss.

Topics: Anesthesia; Animals; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dietary Supplements; Drug Evaluation, Preclinical; Drug Therapy, Combination; Ellagic Acid; Flow Cytometry; Hemorrhage; Herb-Drug Interactions; Ketorolac; Male; Meloxicam; P-Selectin; Phytotherapy; Platelet Activation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles

Although during treatment of arthrosis with meloxicam the level of thromboxan A2 decreases, thrombocyte functions are not affected. Meloxicam in therapeutic doses doesn't increase the risk of haemorrhage. Previously it was suspected that co-administration of salicylates with certain other non-steroid antiinflammatory drugs (NSAIDs) will suppress the effect of salicylate. Van Ryn et al have proved that this is not the case with salicylate plus meloxicam therapy. It is hypothesized that meloxicam loosely binds to the cyclooxygenase-1 (COX-1) enzyme and salicylate can easily replace it.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Hemorrhage; Humans; Meloxicam; Osteoarthritis; Salicylates; Thiazines; Thiazoles