Meloxicam, an oxican derivative, is a member of the enolic acid group of non-steroidal anti-inflammatory drugs (NSAIDs). Meloxicam is chemically designated as 4-hydroxy-2-methyl-N-(5-methyl-2-thiazoyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide. The molecular weight is 351.4. Its empirical formula is C14H13N3O4S2
Mechanism of action
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic activities. The mechanism of action of meloxicam like that of other NSAIDs, may be related to prostaglandin synthetase (cyclo-oxygenase) inhibition.
After multiple oral doses the pharmacokinetics of meloxicam were dose-proportional over the range of 7.5 mg to 15 mg. Mean Cmax was achieved within four to five hours after a 7.5 mg meloxicam tablet was taken under fasted conditions, indicating a prolonged drug absorption. With multiple dosing, steady state concentrations were reached by day 5. A second meloxicam concentration peak occurs around 12 to 14 hours post-dose suggesting biliary recycling.
The mean volume of distribution (Vss) of meloxicam is approximately 10L. Meloxicam is ~99.4% bound to human plasma proteins (primarily albumin) within the therapeutic dose range.
Meloxicam is almost completely metabolized to four pharmacologically inactive metabolites
Meloxicam excretion is predominantly in the form of metabolites and occurs to equal extents in the urine and feces. The mean elimination half-life (t1/2)ranges from 15 hours to 20 hours. The elimination half-life is constant across dose levels indicating linear metabolism within the therapeutic dose range. Plasma clearance ranges from 7 to 9ml/min.
Following a single 15mg dose of meloxicam there was no marked difference in plasma concentrations in subjects with mild (Child-Pugh Class i) and moderate (Child-Pugh Class ii) hepatic impairment compared to healthy volunteers. Protein binding of meloxicam was not affected by hepatic insufficiency. No dose adjustment is necessary in mild to moderate hepatic insufficiency. Patients with severe hepatic impairment (Child-Pugh Class iii) have not been adequately studied.
Meloxicam pharmacokinetics have been investigated in subjects with different degrees of renal insufficiency. Total drug plasma concentrations decreased with the degree of renal impairment while free AUC values were similar. Total clearance of meloxicam increased in these patients probably due to the increase in free fraction leading to an increased metabolic clearance. There is no need for dose adjustment in patients with mild to moderate renal failure. Patients with severe renal insufficiency have not been adequately studied. The use of meloxicam in subject with severe renal impairment is not recommended.
Indications and usage
Carefully consider the potential benefits and risks of meloxicam and other treatment options before deciding to use meloxicam. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
Meloxicam is indicated for relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis.
Meloxicam is indicated for relief of the the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients 2 years of age and older.
Contraindicated in patients with known hypersensitivity
Should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal anaphylactic-like reactions to NSAIDs have been reported in such patients.
Contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Cardiovascular Thrombotic events
Clinical trials of several COX-2 selective and non-selective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke which can be fatal. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective doses should be used for the shortest duration possible.
NSAIDs, including meloxicam, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment throughout the course of therapy
Congestive heart failure and edema
Fluid retention and edema have been observed in some patients taking NSAIDs. Meloxicam should be used with caution in patients with fluid retention, hypertension or heart failure
Gastrointestinal (GI) effects
NSAIDs, including meloxicam can cause serious gastrointestinal adverse events including inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physician should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Advanced renal disease
Treatment with meloxicam is not recommended in patients with advanced renal disease
As with other NSAIDs, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam
NSAID, incluiding meloxicam, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome and toxic epidermal necrolysis, which can be fatal.
In late pregnancy, as with other NSAIDs, meloxicam should be avoided because it may cause premature closure of the ductus arteriosus.
Dosage and administration
Osteoarthritis and Rheumatoid arthritis
Carefully consider potential benefits and risks of meloxicam and other treatment options before deciding to use meloxicam. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. After observing the response to initiate therapy with meloxicam, the dose should be adjusted to suit an individual patient’s need.
For the relief of signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of meloxicam is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.
For the relief of the signs and symptoms of rheumatoid arthritis, the recommended starting and maintenance oral dose of meloxicam is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily. The maximum recommended daily oral dose of meloxicam is 15 mg. Meloxicam may be taken without regard to timing of meals.