Ibuprofen

Ibuprofen is a propionic acid nonselective cyclo-oxygenase inhibitor with analgesic, antipyretic and anti-inflammatory effects. It has the most favourable gastrointestinal and cardiovascular profile among nonselective NSAIDs at analgesic doses, and is the usual first-line NSAID for acute pain, fever and dysmenorrhoea.

Class. Nonselective NSAID (propionic acid derivative).

Mechanism. Reversible inhibition of COX-1 and COX-2, reducing prostaglandin and thromboxane synthesis. The S-enantiomer is the active form.

Pharmacokinetics. Oral bioavailability over 80%. Peak at 1 to 2 hours, delayed by food. Analgesic onset about 30 minutes, duration 4 to 6 hours. Protein binding over 98%. Half-life about 2 hours. Hepatic oxidation (CYP2C9) and glucuronidation with renal excretion of metabolites.

Dose-response. Analgesic effect plateaus near 400 mg a dose; anti-inflammatory effect needs 1.2 to 2.4 g daily.

Indications are mild to moderate pain, fever, dysmenorrhoea, dental and postoperative pain, renal colic (adjunct), inflammatory musculoskeletal conditions, and closure of patent ductus arteriosus in preterm infants.

Adults

• Analgesia, fever, dysmenorrhoea: 200 to 400 mg orally every 6 to 8 hours with food. Maximum 1.2 g daily without supervision; maximum 2.4 g daily when prescribed.
• Inflammatory musculoskeletal disease: 400 to 600 mg three to four times daily; 1.2 to 2.4 g daily in divided doses. Maximum 2.4 g daily.
• Intravenous (postoperative, where available): 400 mg infused over 30 minutes every 6 hours. Hydrate first. Usual duration is under 48 hours. Maximum 2.4 g daily in most practice; some labels allow up to 3.2 g.
• No loading dose. Titrate to the lowest effective dose.

Children over 3 months and over 5 kg

• Oral 5 to 10 mg/kg every 6 to 8 hours. Maximum 30 mg/kg in 24 hours (up to 40 mg/kg in some labels), and not above 2.4 g daily.
• Juvenile idiopathic arthritis (specialist): 30 to 40 mg/kg daily in 3 to 4 divided doses.
• Not for children who are dehydrated, vomiting repeatedly or have suspected dengue or other haemorrhagic fever.

Preterm infants (specialist, neonatal unit). For patent ductus arteriosus, 10 mg/kg intravenously, then 5 mg/kg at 24 and 48 hours.

Gastroprotection. Add a proton pump inhibitor (for example omeprazole 20 mg daily) for age over 65, previous ulcer or bleed, or concurrent anticoagulant, antiplatelet, corticosteroid or SSRI use.

Contraindications. Active or previous peptic ulcer or gastrointestinal bleeding or perforation; previous NSAID-related bleed; severe heart failure; severe renal impairment (creatinine clearance under 30 mL/min); severe hepatic impairment; third trimester; hypersensitivity, including aspirin-exacerbated asthma, rhinosinusitis or urticaria; around coronary artery bypass surgery; active bleeding; suspected dengue until excluded.

Boxed-warning-level risks. Arterial thrombotic events (myocardial infarction and stroke), more evident at 2.4 g daily; gastrointestinal bleeding, ulceration and perforation, which may occur without warning symptoms.

Adverse effects. Common: dyspepsia, nausea, abdominal pain, headache, dizziness, fluid retention and raised blood pressure. Serious: gastrointestinal haemorrhage, acute kidney injury, hyperkalaemia, bronchospasm, anaphylaxis, severe skin reactions, aseptic meningitis (especially in lupus), hepatotoxicity and cytopenias.

Interactions

• Aspirin: ibuprofen can block the antiplatelet effect of low-dose aspirin. Take aspirin at least 30 minutes before, or 8 hours after, ibuprofen.
• Anticoagulants, antiplatelets, corticosteroids, SSRIs: additive bleeding risk.
• ACE inhibitors, angiotensin receptor blockers and diuretics: acute kidney injury and blunted antihypertensive effect (the “triple whammy” when all three are combined).
• Lithium: raised lithium levels. Methotrexate: reduced clearance, serious toxicity at high dose. Ciclosporin and tacrolimus: nephrotoxicity. Tenofovir disoproxil: additive renal injury. Quinolones: seizure risk.

Common prescribing errors. Giving to a hypovolaemic or dehydrated patient; combining two NSAIDs or an NSAID with aspirin for pain; omitting gastroprotection in high-risk patients; continuing after a new rise in creatinine.

Special groups

• Pregnancy: avoid from 20 weeks (foetal renal impairment, oligohydramnios) and absolutely in the third trimester (ductus arteriosus constriction). Before 20 weeks use only when needed, at the lowest dose for the shortest time. Paracetamol is preferred.
• Breastfeeding: low milk concentrations; acceptable for short courses.
• Older adults: higher risk of bleeding, kidney injury and heart failure; start low and add gastroprotection.
• Kidney impairment: creatinine clearance 30 to 59 mL/min, lowest dose for the shortest time with renal function checks; under 30 mL/min, avoid.
• Liver impairment: avoid in severe disease; use caution in mild to moderate.
• Regional: avoid in dehydrating illness, in suspected dengue, and when volume depletion from gastroenteritis is possible. Check creatinine before use in people taking tenofovir disoproxil.

Formulations. Tablets 200, 400 and 600 mg, modified-release capsules, oral suspension 100 mg/5 mL, and intravenous solution where available.

Administration. Oral doses are taken with or after food. Intravenous concentrate must be diluted to 4 mg/mL or less in 0.9% sodium chloride or 5% glucose and infused over at least 30 minutes.

Baseline. Blood pressure, creatinine and eGFR in older adults and those with risk factors, volume status, ulcer history, asthma history and concurrent medicines.

Monitoring. Blood pressure, fluid status and creatinine within 1 to 2 weeks if treatment continues beyond a short course in high-risk patients. Haemoglobin and stool for melaena if gastrointestinal symptoms occur. Liver enzymes if prolonged.

Therapeutic drug monitoring. Not used.

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

Referral and escalation. Melaena, haematemesis, oliguria, severe hypertension or anaphylaxis needs emergency assessment. Persistent need beyond 10 to 14 days warrants review of the underlying cause.