Etoricoxib

Etoricoxib is a highly selective COX-2 inhibitor with once-daily dosing and rapid onset, used for arthritis, acute gout and short-term acute pain. Its main hazards are hypertension and arterial thrombotic events.

Class. Coxib (selective COX-2 inhibitor).

Mechanism. Selective inhibition of COX-2 with minimal effect on platelet thromboxane at therapeutic doses.

Pharmacokinetics. Oral bioavailability about 100%. Peak about 1 hour. Protein binding about 92%. Half-life about 22 hours. Hepatic metabolism mainly by CYP3A4, with renal excretion of metabolites.

Indications are osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute gouty arthritis and short-term relief of acute pain after dental surgery.

Adults and adolescents over 16 years

• Osteoarthritis: 30 mg once daily; if inadequate, 60 mg once daily.
• Rheumatoid arthritis and ankylosing spondylitis: 90 mg once daily.
• Acute gout: 120 mg once daily, used only during the acute symptomatic period. Maximum duration 8 days.
• Acute postoperative dental pain: 90 mg once daily for a maximum of 3 days.
• Maximum 60 mg daily for osteoarthritis and 90 mg daily for the other chronic indications; 120 mg is for acute gout alone.
• No loading dose. Titrate to the lowest effective dose.

Hepatic dose limits. Child-Pugh 5 to 6: maximum 60 mg once daily. Child-Pugh 7 to 9: 30 mg once daily (or 60 mg every second day). Child-Pugh over 9: do not use.

Children. Not advised under 16 years.

Rifampicin. Rifampicin lowers etoricoxib exposure. Dose adjustment is directed by the local label.

Contraindications.

• Uncontrolled hypertension (persistently over 140/90 mmHg).
• Established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or heart failure (class II to IV).
• Active gastrointestinal ulcer or bleeding.
• Severe hepatic impairment.
• Creatinine clearance under 30 mL/min.
• Hypersensitivity to NSAIDs including aspirin-exacerbated respiratory disease.
• Third trimester and breastfeeding.
• Around coronary artery bypass surgery.
• Suspected dengue.
• Inflammatory bowel disease.

Boxed-warning-level risks. Arterial thrombotic events (myocardial infarction, stroke); gastrointestinal bleeding, ulceration and perforation; severe skin reactions; hypertension.

Adverse effects. Common: hypertension, oedema, dyspepsia, headache, dizziness, raised transaminases, fatigue. Serious: myocardial infarction, stroke, heart failure, gastrointestinal haemorrhage, acute kidney injury, hepatitis, anaphylaxis, severe skin reactions and bronchospasm.

Interactions. Warfarin: INR rises, so monitor INR after starting. Rifampicin lowers etoricoxib levels. Raised lithium and methotrexate. Oral contraceptives: ethinyloestradiol exposure increases at the 120 mg dose. Bleeding with aspirin, anticoagulants and corticosteroids. Kidney injury with ACE inhibitors, angiotensin receptor blockers and diuretics. Blunted effect of antihypertensives.

Common prescribing errors. Using in patients with unrecognised hypertension; exceeding 8 days at 120 mg; prescribing to people with cardiovascular disease; omitting hepatic dose limits; adding a second NSAID.

Special groups

• Pregnancy: avoid; risk of foetal renal injury and ductal constriction.
• Breastfeeding: avoid.
• Older adults: lowest dose with blood pressure monitoring.
• Kidney impairment: avoid if creatinine clearance is under 30 mL/min.
• Liver impairment: maximum 60 mg daily (Child-Pugh 5 to 6) or 30 mg daily (Child-Pugh 7 to 9); avoid in severe disease.
• Regional: availability and licensed indications vary; check the local label. Avoid in dehydration and suspected dengue.

Formulations. Tablets 30, 60, 90 and 120 mg.

Administration. Swallow whole with or without food. An empty stomach gives a faster onset when rapid relief is wanted.

Baseline. Blood pressure (must be controlled), cardiovascular history, creatinine and eGFR, liver function, ulcer history and concurrent medicines.

Monitoring. Blood pressure within 2 weeks of starting and periodically. Creatinine in high-risk patients. Liver enzymes if prolonged therapy. INR in people on warfarin.

Therapeutic drug monitoring. Not used.

Stopping thresholds. Stop for sustained blood pressure over 140/90 mmHg, chest pain, new heart failure, gastrointestinal bleeding, jaundice, creatinine rise of 30% or more or severe rash.

Referral and escalation. Hypertensive urgency, cardiovascular symptoms, bleeding, anaphylaxis or oliguria need emergency care. Need beyond the short course in gout or acute pain needs review of the underlying diagnosis.