Although meloxicam inhibits formation of thromboxane A, it does not appear to do so at levels that would interfere with platelet function.A pooled analysis of randomized, controlled studies of meloxicam therapy of up to 60 days duration found that meloxicam was associated with a statistically significantly lower number of thromboembolic complications than the NSAID diclofenac (0.2% versus 0.8% respectively) but a similar incidence of thromboembolic events to naproxen and piroxicam.In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. Cardiovascular
People with hypertension, high cholesterol, or diabetes are at risk for cardiovascular side effects. People with family history of heart disease, heart attack, or stroke should tell their treating physician as the potential for serious cardiovascular side effects is significant. Gastrointestinal
NSAIDs cause and increase the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Elderly patients are at greater risk for serious gastrointestinal events. Mouth
It is recommended to withhold meloxicam use for at least four to six half-lives prior to surgical or dental procedures due to increased risk for taste perversion, ulcerative stomatitis and dry mouth. Mechanism of action
Meloxicam blocks cyclooxygenase (COX), the enzyme responsible for converting arachidonic acid into prostaglandin H2—the first step in the synthesis of prostaglandins, which are mediators of inflammation.
Meloxicam has been shown, especially at low therapeutic doses, to selectively inhibit COX-2 over COX-1.Meloxicam concentrations in synovial fluid range from 40% to 50% of those in plasma. The free fraction in synovial fluid is 2.5 times higher than in plasma, due to the lower albumin content in synovial fluid as compared to plasma. The significance of this penetration is unknown, but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models. Pharmacokinetics
Absorption
The bioavailability of meloxicam is decreased when administered orally compared to an equivalent IV bolus dose. Use of oral meloxicam following a high-fat breakfast increases the mean peak drug levels by about 22%; however, the manufacturer does not make any specific meal recommendations. In addition, the use of antacids does not show pharmacokinetic interactions. Distribution
The mean volume of distribution of meloxicam is approximately 10L. It is highly protein-bound, mainly to albumin. Metabolism
Meloxicam is extensively metabolized in the liver by the enzymes CYP2C9 and CYP3A4 (minor) into four inactive metabolites. Peroxidase activity is thought to be responsible for the other two remaining metabolites. Excretion
Meloxicam is predominantly excreted in the form of metabolites and occurs to equal extents in the urine and feces. Traces of unchanged parent drug are found in urine and feces. The mean elimination half-life ranges from 15 to 20 hours. Specific populations
Geriatrics
Use of meloxicam is not recommended in people with peptic ulcer disease or increased gastrointestinal bleed risk, including those over 75 years of age or those taking medications associated with bleeding risk.