MELOZEN 15

Indications

• Pain and inflammation in musculoskeletal disorders
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis

Dosage

Children: For children aged 16-17 years, the dose is 7.5 mg once daily, increased if necessary up to 15 mg once daily. For children aged 12-17

Adults: The typical adult dosage is 15 mg once daily, reduced to 7.5 mg once daily if necessary.

Mechanism of action

Meloxicam inhibits prostaglandin synthetase (cyclooxygenase 1 and 2) enzymes, resulting in decreased synthesis of prostaglandins that sensitize neuronal pain receptors. This inhibition leads to its analgesic and anti-inflammatory effects. It preferentially inhibits COX-2, which may reduce gastrointestinal irritation compared to non-selective NSAIDs.

Pharmacodynamics

Meloxicam exhibits anti-inflammatory, analgesic, and antipyretic effects. It has been shown to decrease markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), in patients with rheumatoid arthritis. While meloxicam is designed to cause less gastrointestinal irritation due to its COX-2 selectivity, it still carries risks associated with gastrointestinal symptoms, including inflammation, bleeding, and ulceration.

Pharmacokinetics

Meloxicam is well-absorbed following oral administration, with peak plasma concentrations typically reached within 4 to 5 hours. It has a half-life of approximately 15 to 20 hours, allowing for once-daily dosing. The drug is extensively metabolized in the liver, and its metabolites are primarily excreted in the urine. Patients with renal or hepatic impairment may require dose adjustments or careful monitoring due to altered pharmacokinetics.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• History of gastrointestinal bleeding related to previous NSAID therapy
• History of significant renal impairment
• History of coronary artery bypass graft surgery
• History of hypersensitivity to aspirin or any other NSAID, including those who have experienced asthma, angioedema, urticaria, or rhinitis precipitated by these agents

Adverse effects

• Gastrointestinal discomfort
• Gastrointestinal bleeding
• Nausea
• Vomiting
• Headache
• Constipation
• Diarrhea
• Renal impairment
• Cardiovascular events
• Delayed onset of labor
• Potential exacerbation of asthma symptoms

Interactions

• Increased risk of gastrointestinal side effects when used with other NSAIDs
• May interfere with the effects of antihypertensive medications
• Caution advised with anticoagulants due to increased bleeding risk
• May reduce the effectiveness of diuretics

Precautions

• Use with caution in patients with a history of gastrointestinal disorders, such as ulcerative colitis or Crohn's disease
• Use with caution in elderly patients due to increased risk of serious side effects
• Monitor renal function in patients with renal impairment
• Long-term use may lead to decreased female fertility, which is reversible upon discontinuation

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risk of fetal ductus arteriosus closure and potential persistent pulmonary hypertension in the newborn.

Breast-feeding

Use with caution; present in milk in animal studies, manufacturer advises avoiding use during breastfeeding.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Meloxicam 7.5 mg oral tablets
• Meloxicam 15 mg oral tablets
• Meloxicam 500 mg oral suspension

Mechanism of action

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. Meloxicam, an oxicam derivative that is structurally related to piroxicam, is a nonsteroidal anti-inflammatory agent (NSAIA) exhibiting analgesic, antipyretic, and anti-inflammatory actions. In vitro and in vivo studies indicate that meloxicam inhibits the cyclooxygenase-2 (COX-2) isoform of prostaglandin endoperoxide synthase (prostaglandin G/H synthase [PGHS]) to a greater extent than the COX-1 isoform. However, meloxicam's COX-2 selectivity is dose dependent and is diminished at higher dosages. Therefore meloxicam sometimes has been referred to as a "preferential" rather than "selective" COX-2 inhibitor. To investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC), and to explore its mechanism. MTT colorimetry was used to determine the adhesion effect of PMN to HSC. Cell-ELISA and RT-PCR methods were used to determine the expression of ICAM-1 and VCAM-1. Nuclear transcription factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA) method. Meloxicam was found to effectively inhibit TNF-alpha (50 u.mL-1 for 12 hr) and IL-1 beta (50 u.mL-1 for 12 hr)-induced adhesion of PMN to HSC (IC50 3.38 X 10(-7) mol.L-1 and 3.56 X 10(-6) mol.L-1, respectively) in a concentration-dependent manner. ICAM-1 protein and mRNA expression induced by TNF-alpha (50 u.mL-1) were inhibited by meloxicam at 1 X 10(-6)-1 X 10(-5) mol.L-1. The activation of NF-kappa B was also inhibited by meloxicam at 1 X 10(-6)-1 X 10(-5) mol.L-1. These results suggest that meloxicam inhibit TNF-alpha stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-kappa B. /Investigators/ compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E2 (PGE2) production. In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B2 (TXB2) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE2 and 7 alpha-hydroxy-5, 11-diketo-tetranor-prosta-1, 16-dionic acid (PGE-M), the index metabolites of renal and total body PGE2 synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry. Maximum platelet aggregation and TXB2 formation were almost completely inhibited by indomethacin (-87% and -99%, respectively; p < 0.001, each) as compared to control (100%), but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE2 excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE2 excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001). /This/ data shows, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.

Pharmacodynamics

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.