Meloxicam

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve various types of pain, including pain caused by musculoskeletal conditions, osteoarthritis, and rheumatoid arthritis. With a longer half-life than most other NSAIDS, it is a favorable option for those who require once-daily dosing. Meloxicam is available in oral, transdermal, and intravenous formulations. It is a preferential COX-2 inhibitor, purportedly reducing the risk of adverse gastrointestinal tract effects, however, this is a topic of controversy.

Meloxicam is an NSAID used to treat osteoarthritis in adults, rheumatoid arthritis in adults, and juvenile rheumatoid arthritis in pediatrics.

Meloxicam is indicated for the symptomatic treatment of arthritis and osteoarthritis. In addition, it is indicated for the pauciarticular and polyarticular course of Juvenile Rheumatoid Arthritis (JRA) in patients aged 2 years old or above. Off-label uses include the treatment of dental or post-surgical pain. In addition to the above, meloxicam has also been studied in the treatment of neuropathic pain.

Meloxicam, together with the local anesthetic bupivacaine, is indicated for the production of postsurgical analgesia in adult patients for up to 72 hours following bunionectomy, open inguinal herniorrhaphy or total knee arthroplasty.

• Dental Pain
• Neuropathic Pain
• Osteoarthritis (OA)
• Pain
• Inflammatory
• Pauciarticular juvenile rheumatoid arthritis
• Polyarticular juvenile rheumatoid arthritis
• chronic or unspecified
• Postoperative pain
• Rheumatoid Arthritis

Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug.

In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events.

A note on gastrointestinal effects

As meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration. In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those on diclofenac. GI events were found to be less severe in the meloxicam-treated patients.

Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation.

The absolute bioavailability oral capsules after a dose was 89% in one pharmacokinetic study. Cmax was reached 5–6 hours after administration of a single dose given after the first meal of the day. The Cmax doubled when the drug was administered in the fasting state. Despite this, meloxicam can be taken without regard to food, unlike many other NSAIDS.

Meloxicam formulated for instillation with bupivacaine produced varied systemic measures following a single dose of varying strength. In patients undergoing bunionectomy, 1.8 mg of meloxicam produced a C_max of 26 ± 14 ng/mL, a median T_max of 18 h, and an AUC_∞ of 2079 ± 1631 ng*h/mL. For a 9 mg dose used in herniorrhaphy, the corresponding values were 225 ± 96 ng/mL, 54 h, and the AUC_∞ was not reported. Lastly, a 12 mg dose used in total knee arthroplasty produced values of 275 ± 134 ng/mL, 36 h, and 25,673 ± 17,666 ng*h/mL.

The volume of distribution of meloxicam is 10-15L. Because of its high binding to albumin, it is likely to be distributed in highly perfused tissues, such as the liver and kidney. Meloxicam concentrations in synovial fluid, measured after an oral dose, is estimated at 40% to 50% of the concentrations measured in the plasma. This drug is known to cross the placenta in humans.

Meloxicam is about 99.4% protein bound, primarily to albumin.

Meloxicam is mainly eliminated through metabolism. Its metabolites are cleared through renal and fecal elimination. Less than 10 About 1.6% of the parent drug is excreted in the feces.

The half-life of meloxicam is approximately 20 hours, which is considerably longer than most other NSAIDS. It can therefore be dosed without the need for slow-release formulations.

Meloxicam applied together with bupivacaine for postsurgical analgesia had a median half-life of 33-42 hours, depending on dose and application site.

After an oral dose, the total clearance of meloxicam is 0.42–0.48 L/h. The FDA label indicates a plasma clearance from 7 to 9 mL/min. No dose changes are required in mild to moderate renal or hepatic impairment. The use of meloxicam in patients with severe renal or hepatic impairment has not been studied. FDA prescribing information advises against it.

The oral LD50 in rats is 98 mg/kg. Signs and symptoms of overdose with meloxicam may include shallow breathing, seizure, decreased urine output, gastrointestinal irritation, nausea, vomiting, gastrointestinal bleeding, and black tarry stools. In the case of an overdose, offer supportive treatment and attempt to remove gastrointestinal contents. Cholestyramine has been shown to enhance the elimination of meloxicam.

• Avoid alcohol. The risk of gastrointestinal bleeding may be increased.
• Take with or without food. The absorption is unaffected by food.

• Osteoarthritis: 7.5 mg/day. If necessary, in the absence of improvement, the dose may be increased to 15 mg/day.
• Rheumatoid arthritis: 15 mg/day. In elderly patients the recommended dose for long term treatment is 7.5 mg/day.
• Ankylosing spondylitis: 15 mg/day. In elderly patients the recommended dose is 7.5 mg/day.