Meloxicam

Meloxicam is an oxicam NSAID with preferential COX-2 inhibition at low doses, allowing once-daily dosing in osteoarthritis and rheumatoid arthritis. Selectivity is lost at 15 mg daily or more.

Class. NSAID (oxicam), preferential COX-2 inhibitor.

Mechanism. Inhibition of cyclo-oxygenase, with greater activity at COX-2 at 7.5 mg. Little effect on platelet thromboxane at low dose.

Pharmacokinetics. Oral bioavailability about 89%, unaffected by food. Peak 5 to 6 hours. Protein binding over 99%. Half-life about 20 hours. Hepatic metabolism by CYP2C9 (major) and CYP3A4; renal and faecal excretion of inactive metabolites. Steady state in about 3 to 5 days.

Indications are symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Use is also common for chronic musculoskeletal pain.

Adults

• Osteoarthritis: 7.5 mg once daily; if needed, increase to 15 mg once daily.
• Rheumatoid arthritis and ankylosing spondylitis: 15 mg once daily; reduce to 7.5 mg once daily if possible.
• Maximum 15 mg daily. No loading dose.
• Haemodialysis: maximum 7.5 mg daily.
• Older adults or high-risk patients: 7.5 mg daily.

Children. Juvenile idiopathic arthritis (specialist, from 2 years in some regions): 0.125 mg/kg once daily, maximum 7.5 mg. In other regions it is not advised under 16 years.

Parenteral. Intramuscular formulations exist in some markets for short courses; use the local label.

Poor CYP2C9 metabolisers. Start at half the usual dose when genotype or poor response to CYP2C9 substrates is known.

Contraindications. Active or previous gastrointestinal ulcer, bleeding or perforation; severe heart failure; severe renal impairment not on dialysis; severe hepatic impairment; third trimester; aspirin-exacerbated respiratory disease or other NSAID hypersensitivity; around coronary artery bypass surgery; suspected dengue; children under 2 years.

Boxed-warning-level risks. Arterial thrombotic events; gastrointestinal bleeding, ulceration and perforation.

Adverse effects. Common: dyspepsia, nausea, abdominal pain, headache, diarrhoea, oedema and raised blood pressure. Serious: gastrointestinal haemorrhage, acute kidney injury, hyperkalaemia, heart failure, hepatitis, anaphylaxis and severe skin reactions.

Interactions. Bleeding with anticoagulants, antiplatelets, corticosteroids and SSRIs; kidney injury with ACE inhibitors, angiotensin receptor blockers and diuretics; raised lithium and methotrexate levels; nephrotoxicity with ciclosporin, tacrolimus and tenofovir disoproxil. Colestyramine speeds meloxicam elimination.

Common prescribing errors. Assuming COX-2 preference is safe in cardiovascular disease or in people on aspirin; using 15 mg in older adults or in dialysis; adding a second NSAID.

Special groups

• Pregnancy: avoid from 20 weeks and in the third trimester; before 20 weeks use only when needed.
• Breastfeeding: avoid; limited data, ibuprofen preferred.
• Older adults: use 7.5 mg daily with gastroprotection.
• Kidney impairment: avoid if creatinine clearance is under 15 mL/min without dialysis; use caution under 30 mL/min.
• Liver impairment: avoid in severe disease; no adjustment in mild to moderate.
• Regional: avoid in dehydration and suspected dengue. Check creatinine before use in people taking tenofovir disoproxil.

Formulations. Tablets 7.5 and 15 mg, orodispersible tablets, suspension 7.5 mg/5 mL, suppositories and injection in some markets.

Administration. Once daily with or without food; take with a meal if dyspepsia occurs.

Baseline. Blood pressure, creatinine and eGFR, cardiovascular and ulcer history, liver enzymes if chronic disease, concurrent medicines.

Monitoring. Blood pressure and creatinine within 2 weeks of starting in high-risk patients. Haemoglobin if gastrointestinal symptoms develop. Liver enzymes periodically in long-term use.

Therapeutic drug monitoring. Not used.

Stopping thresholds. Stop for gastrointestinal bleeding, creatinine rise of 30% or more, new heart failure or severe hypertension, severe rash or bronchospasm.

Referral and escalation. Inadequate response after 2 weeks at the maximum dose needs review for alternative therapy. Gastrointestinal bleeding, anaphylaxis or oliguria needs emergency assessment.