Celecoxib

Celecoxib is a selective COX-2 inhibitor with a sulphonamide moiety. It spares platelet function and carries a lower rate of upper gastrointestinal complications than nonselective NSAIDs in patients not on aspirin, but it retains cardiovascular and renal risks.

Class. Coxib (selective COX-2 inhibitor).

Mechanism. Selective, reversible inhibition of COX-2. No clinically relevant inhibition of platelet thromboxane at usual doses.

Pharmacokinetics. Peak about 3 hours, delayed by a high-fat meal. Protein binding about 97%. Half-life about 11 hours. Hepatic metabolism mainly by CYP2C9 (minor CYP3A4); inactive metabolites excreted in urine and faeces.

Indications are osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute pain, dysmenorrhoea and juvenile idiopathic arthritis. It is used as a component of multimodal perioperative analgesia in some units.

Adults

• Osteoarthritis: 200 mg once daily, or 100 mg twice daily.
• Rheumatoid arthritis: 100 to 200 mg twice daily.
• Ankylosing spondylitis: 200 mg daily (single or divided); if the response is inadequate after 6 weeks, increase to 400 mg daily.
• Acute pain and dysmenorrhoea (where licensed): 400 mg first dose, then a further 200 mg on day 1 if needed, then 200 mg twice daily as needed.
• Maximum 400 mg daily in most practice. No titration other than use of the lowest effective dose.
• Preoperative single doses of 200 to 400 mg are used in some units; evidence is mixed.

Children over 2 years (juvenile idiopathic arthritis, specialist)

• 10 to 25 kg: 50 mg twice daily.
• Over 25 kg: 100 mg twice daily.

Dose changes

• CYP2C9 poor metabolisers (known genotype): start at half the lowest usual dose.
• Concurrent fluconazole: halve the celecoxib dose.

Contraindications. Hypersensitivity to sulphonamides or NSAIDs, including aspirin-exacerbated respiratory disease; active gastrointestinal ulcer or bleeding; established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or heart failure (class II to IV); severe hepatic impairment; severe renal impairment; third trimester; around coronary artery bypass surgery; suspected dengue.

Boxed-warning-level risks. Arterial thrombotic events (myocardial infarction, stroke), risk rising with dose and duration; gastrointestinal bleeding, ulceration and perforation, with reduced benefit over nonselective NSAIDs when aspirin is also taken.

Adverse effects. Common: dyspepsia, abdominal pain, diarrhoea, headache, dizziness, oedema and hypertension. Serious: myocardial infarction, stroke, heart failure, gastrointestinal bleeding, acute kidney injury, hyperkalaemia, hepatitis, anaphylaxis, severe skin reactions and DRESS.

Interactions. Fluconazole and other CYP2C9 inhibitors raise levels. Bleeding with anticoagulants, aspirin, corticosteroids and SSRIs. Kidney injury with ACE inhibitors, angiotensin receptor blockers and diuretics. Raised lithium and methotrexate. Celecoxib inhibits CYP2D6 and may raise levels of metoprolol and some antidepressants.

Common prescribing errors. Using a coxib for gastrointestinal protection in patients who also take aspirin without a proton pump inhibitor; ignoring a sulphonamide allergy; double-dosing with another NSAID; using it in established cardiovascular disease.

Special groups

• Pregnancy: avoid from 20 weeks and in the third trimester; before 20 weeks use only if necessary.
• Breastfeeding: low milk levels; short use acceptable only if no alternative.
• Older adults: lowest dose, blood pressure and renal checks.
• Kidney impairment: avoid if creatinine clearance is under 30 mL/min.
• Liver impairment: reduce the dose by 50% in moderate impairment (Child-Pugh B); avoid in severe impairment.
• Regional: co-trimoxazole is widely used, so ask about previous sulphonamide reactions; avoid in dehydration and suspected dengue.

Formulations. Capsules 100 and 200 mg.

Administration. Take with food to reduce dyspepsia, and with a meal when 400 mg is used. Capsules may be opened and mixed into apple sauce or similar for swallowing difficulty.

Baseline. Blood pressure, cardiovascular history, creatinine and eGFR, liver function, sulphonamide allergy, aspirin use and concurrent medicines.

Monitoring. Blood pressure and creatinine within 2 weeks in high-risk patients. Liver enzymes if prolonged therapy. Review need at each visit.

Therapeutic drug monitoring. Not used.

Stopping thresholds. Stop for chest pain, new heart failure, uncontrolled hypertension, gastrointestinal bleeding, creatinine rise of 30% or more, jaundice, rash or hypersensitivity.

Referral and escalation. Cardiovascular events, bleeding, anuria or anaphylaxis need emergency care. Persistent need over 3 months needs specialist review.