Piroxicam

Piroxicam is an oxicam NSAID with a very long half-life that allows once-daily dosing. Its gastrointestinal toxicity and serious skin reactions are greater than those of most other NSAIDs, so it is limited to specialist initiation and second-line use in several regions.

Class. Nonselective NSAID (oxicam).

Mechanism. Reversible inhibition of COX-1 and COX-2, with some effect on neutrophil function.

Pharmacokinetics. Well absorbed; peak 3 to 5 hours. Protein binding over 99%. Half-life about 50 hours, so steady state takes 7 to 12 days and effects persist for days after stopping. Hepatic CYP2C9 hydroxylation and glucuronidation; renal and faecal excretion.

Where it is still used, indications are symptomatic osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute musculoskeletal conditions.

Adults

• Chronic arthritis: 20 mg once daily. Maximum 20 mg daily in most practice; some labels permit 30 mg daily.
• Acute gout: 40 mg once daily for 4 to 6 days.
• Acute musculoskeletal disorders: 40 mg once daily for the first 2 days, then 20 mg once daily for 7 to 14 days.
• Intramuscular: 20 mg once daily in some markets for a short course.
• No loading dose beyond the first-day doses given here; no formal titration.

Children. Not advised outside specialist rheumatology practice.

Older adults. Avoid where possible; if used, 10 mg to 20 mg daily with gastroprotection.

Duration. Review at 14 days for acute indications; long-term use is not preferred.

Contraindications. Active or previous gastrointestinal ulcer, bleeding or perforation; history of severe skin reaction to piroxicam; severe heart failure; severe renal or hepatic impairment; third trimester; aspirin-exacerbated respiratory disease or other NSAID hypersensitivity; around coronary artery bypass surgery; concurrent anticoagulants; suspected dengue.

Boxed-warning-level risks. Gastrointestinal bleeding, ulceration and perforation (higher than most NSAIDs); arterial thrombotic events; severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, usually early in treatment.

Adverse effects. Common: dyspepsia, nausea, abdominal pain, oedema, headache, tinnitus. Serious: gastrointestinal haemorrhage, acute kidney injury, hepatitis, severe skin reactions, photosensitivity, anaphylaxis and cytopenias.

Interactions. Bleeding with anticoagulants, antiplatelets, corticosteroids and SSRIs; kidney injury with ACE inhibitors, angiotensin receptor blockers and diuretics; raised lithium and methotrexate; reduced clearance with CYP2C9 inhibitors. Colestyramine hastens elimination.

Common prescribing errors. Expecting prompt effect from dose changes (steady state is slow); restarting after a skin reaction; prescribing for a long course in older adults; combining with another NSAID.

Special groups

• Pregnancy: avoid from 20 weeks and in the third trimester.
• Breastfeeding: avoid; prefer ibuprofen.
• Older adults: avoid.
• Kidney impairment: avoid if creatinine clearance is under 30 mL/min.
• Liver impairment: avoid in severe disease.
• Regional: avoid in dehydration and suspected dengue; avoid in people taking tenofovir disoproxil without renal monitoring.

Formulations. Capsules 10 and 20 mg, dispersible tablets 10 and 20 mg, suppositories and injection in some markets, topical gel.

Administration. Once daily with food. Ensure the full capsule contents are swallowed.

Baseline. Blood pressure, creatinine, ulcer and cardiovascular history, liver enzymes, concurrent medicines and a history of drug rash.

Monitoring. Skin and mucosa during the first weeks. Blood pressure and creatinine within 2 weeks in high-risk patients. Haemoglobin if gastrointestinal symptoms develop.

Therapeutic drug monitoring. Not used.

Stopping thresholds. Stop at the first rash, mucosal lesion or blistering, or for gastrointestinal bleeding, creatinine rise of 30% or more, new heart failure or bronchospasm.

Referral and escalation. Any rash with fever or mucosal involvement needs emergency assessment for severe cutaneous adverse reaction. Gastrointestinal bleeding needs urgent endoscopy planning.