Ibuprofen

Registered South African indications:

• Pain
• Inflammation
• Fever

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity reactions after taking aspirin or other non-steroidal anti-inflammatory drugs
• Third trimester of pregnancy
• Severe renal impairment
• Severe hepatic impairment
• History of gastrointestinal bleeding or perforation related to previous non-steroidal anti-inflammatory therapy
• Active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding)
• Increased tendency to bleeding  
• Severe heart failure (NYHA Class IV)

Cautions

• First and second trimester of pregnancy
• Breastfeeding
• Female patients of reproductive potential
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Dehydration
• History of gastrointestinal disease
• Ulcerative colitis or Crohn's disease
• History of gastrointestinal ulcer, particularly if complicated with haemorrhage or perforation
• Current, or with a history of, bronchial asthma, chronic rhinitis or allergic diseases
• Cardiac impairment
• History of cardiac failure (NYHA II-III)
• Hypertension
• Risk of arterial thrombotic events (particularly at a high dose)
• Ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease
• Risk factors for cardiovascular events
  - Hypertension
  - Hyperlipidaemia
  - Diabetes mellitus
  - Smoking
• Systemic lupus erythematosus and mixed connective tissue disease
• High dose therapy
• Long-term therapy
• Patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion
• Varicella infections
• Frequent or daily headaches despite (or because of) the regular use of analgesic medication
• Presence of an infection
• Galactose intolerance (certain formulations)
• Lapp lactase deficiency (certain formulations)
• Glucose-galactose malabsorption (certain formulations)

Forms available in SA and covered in this monograph: tab, retard tab (ret tab), cap

Pain - mild to moderate

• Oral (tab, ret tab, cap): 1200-1800mg, dly in divided doses; Maintenance range: 600-1200mg, dly in divided doses. Max: 2400mg/24hrs

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In severe or acute conditions, it can be advantageous to increase the dose until the acute phase is brought under control, provided that the total daily dose ≤2400mg, in divided doses

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Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms

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Specific doses based on individual indications

Osteoarthritis
Rheumatoid arthritis

• Oral (tab): 400-800mg, 6-8hrly; Max: 2400mg/24hrs in acute phase; Max: 1200mg/24hrs in maintenance dose
• Oral (ret tab): 1600mg, given as a single dose early evening; In severe or acute conditions; Increase dose to 2400mg, taken in two divided doses, if needed (manufacturer recommendation)

Dysmenorrhoea

• Oral (tab): 400mg, 6-8hrly; Max: 1200mg/24hrs 
• Oral (cap): 400mg, 8hrly; Max: 1200mg/24hrs 

Migraine

• Oral (tab): 400mg, at onset of symptoms; Max: 800mg/24hrs 

Acute gout

• Oral (tab) : 600-800mg, 6-8hrly; Max: 2400mg/24hrs; Max duration: 3 days

Fever

• Oral (cap): 400mg, 8hrly; Max: 1200mg/24hrs; Max duration: 3 days

Ankylosing spondylitis
Non-articular rheumatism
Periarticular conditions
Soft-tissue injuries

• Oral (ret tab): 1600mg, given as a single dose early evening; In severe or acute conditions; Increase dose to 2400mg, taken in two divided doses, if needed (manufacturer recommendation)

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To be taken preferably with or after food, with plenty of fluid

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Use the lowest effective dose for the shortest possible duration of treatment

Paed. forms available in SA and covered in this monograph: sus

Pain - mild to moderate
Fever 

Younger than 3 months

• Not established for use

Between 3 months (≥5 kg) - 12 years

Oral (sus) 

• 20-30mg/kg/day, 6-8hrly if needed

Age	Weight	Dosing Interval
3-6 months	5-7.6 kg	50mg, 8hrly
6-12 months	7.7-9 kg	50mg, 6-8hrly
1-3 years	10-16 kg	100mg, 8hrly
4-6 years	17-20 kg	150mg, 8hrly
7-9 years	21-30 kg	200mg, 8hrly
10-12 years	31-40 kg	300mg, 8hrly

Older than 12 years

• See adult dosage

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Doses should be taken at least 4 hours apart. The recommended dose should not be exceeded

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Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms

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For children <6 months: if symptoms worsen or persist for >24 hours (3 doses), consult a doctor

For children >6 months: if symptoms worsen or persist for >3 days, consult a doctor

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Post-immunisation fever 

• Oral (sus) Initial: 50mg; Repeat dose after 6hrs if needed; Max: 100mg/24hrs

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If the fever is not reduced, consult a doctor

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Juvenile rheumatoid arthritis

• Oral (sus): 30-40mg/kg/day in 3-4 divided doses

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 To be taken preferably with or after food

Pregnancy

• First and second trimester: Caution; not recommended
• Third trimester: Contraindicated
• Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, the administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre and post-implantation losses and embryo/foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period
• During the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible
• During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to the following:
  - Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)
  - Renal dysfunction, which may progress to renal failure with oligohydramnios
• At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to the following:
  - Possible prolongation of bleeding time
  - Inhibition of uterine contractions, which may result in delayed or prolonged labour
• Consequently, ibuprofen is contraindicated during the third trimester of pregnancy

Breastfeeding

• Caution
• In the limited studies available, NSAIDs can appear in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding

Fertility

• The use of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ibuprofen should be considered

Renal Impairment

• Mild to moderate: Caution; dose adjustment recommended
• Severe: Contraindicated

Renal Impairment	Dose
Mild to moderate	Reduce dose by 50%; Max duration: 10 days
Severe	Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
  The dose should be reduced by 50% in patients with elevated hepatic enzymes
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended
  The lowest effective dose should be used and for the shortest possible duration

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Paraesthesia
• Somnolence
• Insomnia
• Anxiety
• Depression
• Confusional state
• Fatigue
• Aseptic meningitis

Cardiovascular Disorders

• Cardiac failure
• Myocardial infarction
• Hypertension
• Oedema

Respiratory Disorders

• Asthma
• Bronchospasm
• Dyspnoea
• Rhinitis

Gastrointestinal Disorders

• Dyspepsia
• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Flatulence
• Constipation
• Melaena
• Haematemesis
• Gastrointestinal haemorrhage
• Gastritis
• Duodenal ulcer
• Gastric ulcer
• Mouth ulceration
• Gastrointestinal perforation
• Pancreatitis
• Exacerbation of colitis
• Exacerbation of Crohn's disease

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Hepatic failure
• Abnormal hepatic function

Genitourinary Disorders

• Nephrotoxicity
  - Tubulointerstitial nephritis
  Nephrotic syndrome
• Renal failure

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritus
• Purpura
• Angioedema
• Photosensitivity reaction
• Erythema multiforme
• Bullous reactions
  - Stevens-Johnson syndrome
  - Toxic epidermal necrolysis
• Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
• Acute generalised exanthematous pustulosis (AGEP)

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Anaphylactic reaction
• Leukopenia
• Thrombocytopenia
• Neutropenia
• Agranulocytosis
• Aplastic anaemia
• Haemolytic anaemia

Sensory Disorders

• Visual impairment
• Optic neuritis
• Toxic optic neuropathy
• Impaired hearing
• Tinnitus
• Vertigo

• Antihypertensives
• ACE inhibitors
• Angiotensin-II receptor antagonists
• Beta-blockers
• Diuretics
• Cardiac glycosides
• Cholestyramine
• Lithium
• Methotrexate
• Ciclosporin
• Mifepristone
• Cyclooxygenase-2 selective inhibitors
• Aspirin
• Corticosteroids
• Anticoagulants
• Warfarin
• Quinolone antibiotics
• Sulfonylureas
• Antiplatelet agents
• Selective serotonin reuptake inhibitors
• Tacrolimus
• Zidovudine
• Aminoglycosides
• Ginkgo biloba
• CYP2C9 inhibitors
• Voriconazole
• Fluconazole
• Alcohol

None routine. Specific cases may require

• Renal function
• Hepatic function
• Blood pressure
• Cardiac function
• Full blood count
• Weight
• Ophthalmic examination

Medication overuse headache (MOH)

• The diagnosis of MOH should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of analgesic medication. Patients with MOH should not be treated by increasing the dose of the analgesic and, rather, in such cases, the use of analgesics should be discontinued

Risk of GI bleeding, ulceration or perforation

• The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest dose available
• Combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered for these patients and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk

Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and anti-pyretic activity. The therapeutic effect, as a non-steroidal anti-inflammatory drug (NSAID), is thought to result from its inhibitory effect on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

Tablet 200mg

• Austell Ibuprofen (Austell)
• Austifen (Austell)
• Betagesic (Adcock Ingram)
• Betaprofen (Ranbaxy Pharmaceuticals)
• Brufen (Abbott) originator
• Dynofen (Akacia)
• Iboflam (Pharmacorp)
• Ibu 200 (Innovata)
• Ibucare (Austell)
• Ibucine (Pharmaceutical Contr)
• Ibunate (Gulf Drug)
• Ibuprofen Reckitt 200 (Reckitt Benckiser)
• Ibusor (Indo)
• Inza (Pharmacare)
• Lenafen (Pharmacare)
• Nurofen (Reckitt Benckiser)
• Ranfen (Ranbaxy)
• Unifen (Unimed Healthcare)

Capsule 200mg

• Advil liqui-gel (Pfizer) originator

Tablet 400mg

• Adco-ibuprofen (Adcock Ingram)
• Austell ibuprofen (Austell)
• Austifen (Austell)
• Betaprofen fc (Ranbaxy Pharmaceuticals)
• Bren (Medicine Developers)
• Brufen (Abbott) originator
• Ibucare (Austell)
• Ibucine (Pharmaceutical Contr)
• Inza (Pharmacare)
• Nurofen Period Pain (Reckitt Benckiser) originator
• Ranfen (Ranbaxy SA)
• Unifen 400 (Svizera SA)

Capsule 400mg

• Advil liqui-gel (Pfizer) originator

Tablet 600mg

• Brufen (Abbott) originator
• Ibucare (Austell)
• Sandoz-Ibuprofen (Sandoz SA)

Tablet 800mg

• Brufen Retard (Abbott) originator

Suspension (per 5ml) 100mg 

• Brufen (Abbott) originator
• Ibucine Paediatric Suspension (Pharmaceutical Contr)
• Ibugesic (Cipla Medpro)
• Inflamax (Pharmaceutical Contr)
• Nurofen for children sugar free (Reckitt Benckiser) originator
• Nurofen for children Strawberry (Reckitt Benckiser) originator

Also available in the following forms: Gel and injection.

COMBINATION PREPARATIONS

Ibuprofen/ Paracetamol

Tablet 200mg/350mg

• Ibumol (Pharmacare) originator

Tablet 400mg/325mg 

• Mypaid forte (Adcock Ingram) originator

Capsule 200mg/250mg

• Dentopain (Sandoz)
• Ibupain (Sandoz)
• Mypaid (Adcock Ingram) originator
• Panado Plus (Adcock)

Syrup (per 10ml) 200mg/250mg

• Ibumol (Pharmacare)
• Lotem (Adcock Ingram) originator

Paracetamol/ Codeine/ Ibuprofen

Capsule 250mg/10mg/200mg

•  Dentopain Forte (Sandoz)
•  Gen-Payne(Adcock Ingram)
•  Ibupain Forte (Sandoz)
•  Myprodol (Adcock Ingram) originator

Capsule 350mg/10mg/200mg 

• Mybucod (Pharmacare)
• Mybulen (Pharmacare)

Suspension (per 10ml) 250mg/200mg

• Mybulen (Pharmacare)
• Myprodol (Adcock) originator