Ibuprofen

Oral
Pain and inflammation associated with musculoskeletal and joint disorders
Adult: For short-term symptomatic relief of dysmenorrhoea, dental pain, post-operative pain, headache, low back pain, neuralgia, rheumatic disease (e.g. rheumatoid arthritis, ankylosing spondylitis, osteoarthritis), peri-articular conditions (e.g. capsulitis, bursitis, tendinitis, tenosynovitis), and soft-tissue injuries (e.g. sprains, strains): As conventional tab/cap, effervescent granules, oral susp:1,200-1,800 mg daily in divided doses. Max: 2,400 mg daily. As modified-release tab: 1,600 mg once daily (preferably in the early evening). In severe or acute cases, may increase to 2,400 mg daily, given in 2 divided doses. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Child: >12 yearsSame as adult dose. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Mild to moderate pain
Adult: For short-term symptomatic relief of dysmenorrhoea, dental pain, post-operative pain, headache, low back pain, neuralgia, rheumatic disease (e.g. rheumatoid arthritis, ankylosing spondylitis, osteoarthritis), peri-articular conditions (e.g. capsulitis, bursitis, tendinitis, tenosynovitis), and soft-tissue injuries (e.g. sprains, strains): As conventional tab/cap, effervescent granules, oral susp:1,200-1,800 mg daily in divided doses. Max: 2,400 mg daily. As modified-release tab: 1,600 mg once daily (preferably in the early evening). In severe or acute cases, may increase to 2,400 mg daily, given in 2 divided doses. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Child: >12 yearsSame as adult dose. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Juvenile rheumatoid arthritis
Child: As conventional tab/cap or oral susp: 30-40 mg/kg daily in 3-4 divided doses. Max: 2,400 mg daily. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Fever
Adult: As conventional tab/cap, effervescent granules: 200 mg 4-6 hourly, may increase to 400 mg as necessary. Max: 1,200 mg daily. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Child: As oral susp: 3-5 months weighing >5 kg: 50 mg tid. Max: 24 hours; 6-11 months 50 mg 3-4 times daily; 1-3 years 100 mg tid; 4-6 years 150 mg tid; 7-9 years 200 mg tid; 10-11 years 300 mg tid; >12 years Same as adult dose. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Post-immunisation pyrexia
Child: 50 mg, a second dose of 50 mg may be given after 6 hours if necessary.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Mild to moderate pain
Child: For short-term symptomatic relief of sore throat, teething pain, toothache, earache, headache, minor aches, and soft-tissue injuries (e.g. sprains): As oral susp: 3-5 months weighing >5 kg: 50 mg tid. Max: 24 hours; 6-11 months 50 mg 3-4 times daily; 1-3 years 100 mg tid; 4-6 years 150 mg tid; 7-9 years 200 mg tid; 10-12 years 300 mg tid. In severe symptoms, 30 mg/kg daily in 3 or 4 divided doses. Max: 2,400 mg. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Inflammation
Child: For short-term symptomatic relief of sore throat, teething pain, toothache, earache, headache, minor aches, and soft-tissue injuries (e.g. sprains): As oral susp: 3-5 months weighing >5 kg: 50 mg tid. Max: 24 hours; 6-11 months 50 mg 3-4 times daily; 1-3 years 100 mg tid; 4-6 years 150 mg tid; 7-9 years 200 mg tid; 10-12 years 300 mg tid. In severe symptoms, 30 mg/kg daily in 3 or 4 divided doses. Max: 2,400 mg. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Migraine
Adult: As conventional tab/cap: 200-400 mg tid as necessary. Acute migraine attacks: 400 mg as a single dose, to be given at the onset of symptoms. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Intravenous
Patent ductus arteriosus
Child: As ibuprofen lysine: To close clinically significant patent ductus arteriosus in premature infants (≤32 weeks) weighing 500-1,500 g when usual medical management (e.g. fluid restriction, diuretics, respiratory support) is ineffective: Initially, 10 mg/kg followed by 2 further doses of 5 mg/kg each after 24 and 48 hours. All doses are to be given via IV infusion over 15 minutes. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.
Reconstitution: IV: Dilute with appropriate amount of NaCl 0.9% inj, dextrose 5% inj, or lactated ringers solution to prepare the desired concentration. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).

Intravenous
Fever
Adult: For short-term symptomatic treatment when administration by IV route is clinically justified or when other routes of administration are not possible: Initially, 400 mg, may be followed by 400 mg 4-6 hourly or 100-200 mg 4 hourly as necessary via IV infusion over 30 minutes. Max: 3,200 mg daily. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Child: For short-term symptomatic treatment when administration by IV route is clinically justified or when other routes of administration are not possible: 6-9 years weighing 20-29 kg: 200 mg tid. Max: 600 mg; 10-11 years weighing 30-39 kg: 200 mg 4 times daily. Max: 800 mg; 12-17 years weighing >40 kg: 200-400 mg tid. Max: 1,200 mg. All doses to be given via IV infusion over 30 minutes. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.
Reconstitution: IV: Dilute with appropriate amount of NaCl 0.9% inj, dextrose 5% inj, or lactated ringers solution to prepare the desired concentration. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).

Intravenous
Pain
Adult: For short-term symptomatic treatment of acute moderate pain, when administration by IV route is clinically justified or when other routes of administration are not possible: 400-800 mg 6 hourly as necessary via IV infusion over 30 minutes. Max: 3,200 mg daily. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Child: For short-term symptomatic treatment of acute moderate pain, when administration by IV route is clinically justified or when other routes of administration are not possible: 6-9 years weighing 20-29 kg: 200 mg tid. Max: 600 mg; 10-11 years weighing 30-39 kg: 200 mg 4 times daily. Max: 800 mg; 12-17 years weighing >40 kg: 200-400 mg tid. Max: 1,200 mg. All doses to be given via IV infusion over 30 minutes. Use the lowest effective dose for the shortest duration of time. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.
Reconstitution: IV: Dilute with appropriate amount of NaCl 0.9% inj, dextrose 5% inj, or lactated ringers solution to prepare the desired concentration. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).

Topical/Cutaneous
Pain and inflammation associated with musculoskeletal and joint disorders
Adult: For short-term symptomatic relief of backache, rheumatic and muscular pain, sprains, strains and sports injuries: As 5% or 10% gel: Apply 50-125 mg (4-10 cm of 5% gel or 2-5 cm 10% gel) onto the affected area up to 4 times daily, allow at least 4 hours intervals between successive applications.
Child: >12 years Same as adult dose.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Special Populations: Pharmacogenomics: Ibuprofen is often administered as a racemic mixture of its 2 enantiomers (R)-ibuprofen and (S)-ibuprofen where only the (S)-ibuprofen inhibits the cyclooxygenase enzymes. CYP2C9 isoenzyme is the primary enzyme metabolising (S)-ibuprofen. CYP2C9 is a highly polymorphic gene which may influence metabolism and clearance of ibuprofen, thus affecting drug exposure and potential safety. Genetic testing may be considered. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of March 2020: CYP2C9 normal metaboliser Patient with normal metabolism. CPIC recommends to initiate treatment with the recommended starting dose. CYP2C9 intermediate metaboliser (activity score of 1.5) Patient with mildly reduced metabolism. CPIC recommends to initiate treatment with the recommended starting dose. Use the lowest effective dosage for the shortest duration (in accordance with prescribing information and consistent with individual patient treatment goals). CYP2C9 intermediate metaboliser (activity score of 1) Patient with moderately reduced metabolism where higher plasma concentrations may increase the risk of toxicities. CPIC recommends to initiate treatment with the lowest recommended starting dose. Cautiously titrate dose upward to clinical effect or maximum recommended dose. Use the lowest effective dosage for the shortest duration (in accordance with prescribing information and consistent with individual patient treatment goals). Monitor for adverse events (e.g. blood pressure, kidney function) during therapy. CYP2C9 poor metaboliser Patient who has significantly reduced metabolism and prolonged half-life where higher plasma concentrations may increase the risk and severity of toxicities. CPIC recommends to initiate therapy with 25-50% of the lowest recommended starting dose. Cautiously titrate dose upward to clinical effect or 25-50% of the maximum recommended dose. Use the lowest effective dosage for the shortest duration (in accordance with prescribing information and consistent with individual patient treatment goals). Upward dose titration should not occur until after steady-state is reached (at least 5 days following 1st dose). Monitor for adverse events (e.g. blood pressure, kidney function) during therapy. Alternatively, may consider other therapy not metabolised by CYP2C9. CYP2C9 According to CPIC, CYP2C9*1 is a normal function allele. Individuals carrying CYP2C9*1 allele in combination with another normal function allele may have an increased metabolism of ibuprofen as compared to those carrying at least 1 copy of a decreased or no function allele. However, other genetic and clinical factors may also influence the metabolism of ibuprofen. According to CPIC, CYP2C9*2 is a decreased function allele. Individuals carrying CYP2C9*2 allele in combination with a normal, decreased allele, or no function allele may have decreased metabolism of ibuprofen as compared to those with 2 normal function alleles. However, other genetic and clinical factors may also influence the metabolism of ibuprofen. According to CPIC, CYP2C9*3 is a no function allele. Individuals carrying the CYP2C9*3 allele in combination with a normal, decreased, or no function allele may have decreased metabolism of ibuprofen as compared to those with 2 normal function alleles. However, other genetic and clinical factors may also influence the metabolism of ibuprofen.

Should be taken with food.

Hypersensitivity to ibuprofen; history of hypersensitivity reaction (e.g. bronchospasm, asthma, urticaria, angioedema, rhinitis) to aspirin or other NSAIDs. History of gastrointestinal bleeding, perforation, or ulceration related to NSAID therapy; active, or history of recurrent peptic ulcer or gastrointestinal haemorrhage (≥2 distinct episodes of proven ulceration or bleeding); conditions involving an increased tendency to bleeding; application on broken or damaged skin (topical). Ibuprofen lysine: Proven or suspected infection that is left untreated; congenital heart disease whom patency of PDA is necessary for satisfactory pulmonary or systemic blood flow (e.g. pulmonary artesia, severe tetralogy of Fallot, severe coarctation of the aorta); thrombocytopenia, coagulation defects, confirmed or suspected necrotising enterocolitis. Severe heart failure (New York Heart Association Class IV). Patients undergoing CABG surgery. Severe renal and hepatic impairment. Pregnancy (3rd trimester).

Patient with history of ulcer (especially if complicated with haemorrhage or perforation); history of ulcerative colitis or Crohn's disease; history of bronchial asthma, chronic rhinitis, allergic disease; CV disease, risk factors of CV disease (e.g. mild to moderate CHF, ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, CVA, hypertension, hyperlipidaemia, diabetes mellitus, smoking); recent MI, SLE, mixed connective tissue disorders, acute intermittent porphyria, coagulation disorder, varicella infection; elevated total bilirubin (ibuprofen lysine). Dehydrated, hypovolaemic patients; heavy alcohol drinkers. CYP2C9 intermediate or poor metabolisers; patients carrying CYP2C9*1, CYP2C9*2, or CYP2C9*3 allele. Patient undergoing surgery. Mild to moderate renal and hepatic impairment. Children and elderly. Pregnancy (1st and 2nd trimester) and lactation. Patient Counselling This drug may cause dizziness, drowsiness, fatigue, or visual disturbances, if affected, do not drive or operate machinery. Avoid excessive exposure of treated area to sunlight (topical). Monitoring Parameters Obtain CBC, chemistry profile, occult blood loss and periodic LFTs. Monitor response (e.g. pain, range of motion, grip strength, mobility, ADL function), inflammation; renal function (e.g. urine output, serum BUN and creatinine), blood pressure. Assess for weight gain, oedema, bleeding, bruising, gastrointestinal effects (e.g. abdominal pain, bleeding, dyspepsia), mental confusion or disorientation. Perform periodic ophthalmic exams (prolonged therapy).

Significant: New-onset hypertension or exacerbation of hypertension, platelet aggregation, prolong bleeding time, elevated transaminase levels, hyperkalaemia, drowsiness, dizziness, blurred or diminished vision, scotomata, changes in colour vision; photosensitivity (topical); renal papillary necrosis (prolonged use), mask symptoms of infection, Na and fluid retention, oedema, risk for impairment of female fertility. Rarely, aseptic meningitis, severe blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia). Ear and labyrinth disorders: Tinnitus. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, flatulence, diarrhoea, dyspepsia, constipation, melaena, haematemesis. General disorders and administration site conditions: Fatigue; pain and burning sensation in the administration site (inj). Investigations: Increased lactate dehydrogenase (inj). Metabolism and nutrition disorders: Hypokalaemia, hypernatraemia, hypoalbuminaemia (inj). Nervous system disorders: Headache. Psychiatric disorders: Nervousness. Renal and urinary disorders: Urinary retention (inj). Skin and subcutaneous tissue disorders: Rash, pruritus. Vascular disorders: Hypotension (inj).
Potentially Fatal: CV thrombotic events (e.g. MI or stroke), gastrointestinal ulceration, inflammation, perforation or haemorrhage; rarely, severe hepatic reactions (e.g. fulminant hepatitis, liver necrosis, hepatic failure); very rarely, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalised exanthematous pustulosis (AGEP); drug eosinophilia and systemic symptoms (DRESS) or multiorgan hypersensitivity reactions.

Symptoms: Headache, drowsiness, dizziness, loss of consciousness, convulsions, disorientation, excitation, fainting, tinnitus, nausea, vomiting, abdominal pain, diarrhoea, gastrointestinal bleeding, nystagmus, hypothermia, hypotension, bradycardia, tachycardia, apnoea, CNS and respiratory depression, acute renal failure, liver damage, lethargy, metabolic acidosis, prolonged prothrombin time or INR, coma. Management: Supportive and symptomatic treatment. Consider giving activated charcoal, inducing emesis with ipecac syrup, or performing gastric lavage within 1 hour of ingestion. Ensure good urine output. Monitor renal and liver function. Administer IV diazepam for frequent or prolonged convulsions.

May increase risk of ulceration or bleeding with other NSAIDs, oral corticosteroid, anticoagulants (e.g. warfarin), anti-platelet (e.g. aspirin), SSRIs. May reduce the effect of antihypertensives (e.g. ACE inhibitors, angiotensin II receptor antagonist, β blockers); natriuretic effect of diuretics. May increase the toxicity and plasma concentration of cardiac glycosides. Decreases excretion of lithium, methotrexate, aminoglycosides. Increased risk of nephrotoxicity with ciclosporin, tacrolimus. May increase the risk of convulsions with quinolone antibiotics. May potentiate the effects of sulfonylureas. Increased risk of haematological toxicity with zidovudine. Concomitant use with CYP2C9 inhibitors (e.g. fluconazole, vorizonazole) may increase plasma concentration of ibuprofen.

Food intake decreases absorption rate. May increase risk of bleeding with Ginkgo Biloba. May increase the risk of gastrointestinal bleeding with alcohol.

May alter the result of urine detection of phencyclidine. May produce a false-positive aldosterone/renin ration (ARR).

Ibuprofen, an NSAID, has analgesic, anti-inflammatory and antipyretic properties. It inhibits cyclooxygenase-1 and 2 thereby, reducing the production of prostaglandin precursors.
Onset: Oral: Analgesic: Within 30-60 minutes.
Duration: Antipyretic: 6-8 hours (oral).
Absorption: Rapidly absorbed from the gastrointestinal tract; partially into the skin. Food intake decreases absorption rate. Bioavailability: 80%. Time to peak plasma concentration: 1-2 hours (tab); 1 hour (oral susp).
Distribution: Enters breast milk. Volume of distribution: 0.12 L/kg (oral). Plasma protein binding: >99%.
Metabolism: Metabolised in the liver via oxidation.
Excretion: Mainly via urine (45-80% as metabolites, approx 1% as unchanged drug, 14% as conjugated); faeces. Elimination half-life: Approx 2 hours (oral); 2.22-2.44 hours (IV).

Intravenous: Solution for infusion: Store between 15-30°C. Protect from light. Oral: Store below 25°C. Protect from moisture. Topical/Cutaneous: Store below 25°C. Protect from moisture.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

G02CC01 - ibuprofen ; Belongs to the class of antiinflammatory products for vaginal administration used in the treatment and prevention of inflammation.
M02AA13 - ibuprofen ; Belongs to the class of non-steroidal antiinflammatory preparations for topical use. Used in the treatment of joint and muscular pains.
M01AE01 - ibuprofen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.
C01EB16 - ibuprofen ; Belongs to the class of other cardiac preparations.
R02AX02 - ibuprofen ; Belongs to the class of other throat preparations.