IBUPROFEN

Posology During short-term use, if symptoms persist or worsen the patient should be advised to consult a doctor. 4). 4). If in children and adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

If in adults the product is required for more than 10 days, or if the symptoms worsen the patient should consult your doctor.

Children and Adolescents between 12 and 18 years:

Take 1 or 2 tablets with water, up to 3 times a day as required.

Adults:

Take 1 or 2 tablets with water, up to three times a day as required. Leave at least four hours between doses. Do not take more than 1200mg (6 tablets) in any 24 hour period.

Children under 12 years of age:

Not recommended. Method of administration For oral administration and short term use only. The tablets should be swallowed whole with a drink of water.

Adverse events which have been associated with Ibuprofen are given below, listed by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse events are presented in order of decreasing seriousness. The following list of adverse effects relates to those experienced with ibuprofen at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

The adverse events observed most often are gastrointestinal in nature. Adverse events are mostly dose-dependent, in particular the risk of occurrence of gastrointestinal bleeding is dependent on the dosage range and duration of treatment.

4).

Immune system disorders:

Uncommon: hypersensitivity reactions1 with urticaria and pruritus Very rare: Severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock) Not known: Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea Blood and lymphatic system disorders: Very rare: Haematopoietic disorders (anaemia, hemolytic anemia, aplastic anemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis).

First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained nose and skin bleeding and bruising.

Skin and subcutaneous tissue disorders:

Uncommon: Various skin rashes Very rare: Severe cutaneous adverse reactions (SCARs) (including Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis).

Not known:

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) and Acute Generalised Exanthematous Pustulosis (AGEP), Photosensitivity reactions Nervous system disorders: Uncommon: Headache Very rare: Aseptic Meningitis2 Cardiac disorders: Not known: Cardiac failure and oedema, angina pectoris, Kounis syndrome Vascular Disorders: Not known: Hypertension Respiratory, thoracic and mediastinal disorders: Very rare: Asthma, bronchospasm, dyspnoea and wheezing Gastrointestinal disorders: Uncommon: Abdominal pain, nausea and dyspepsia Rare: Diarrhoea, flatulence, constipation and vomiting Very rare: Peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly.

4) Hepatobiliary disorders: Very rare: Liver disorders, especially in long-term treatment, hepatitis and jaundice Metabolism and Nutrition disorders: Not known: Hypokalaemia3, Decreased Appetite Renal and urinary disorders: Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Haematuria, interstitial nephritis, nephrotic syndrome, proteinuria Not known:

Renal insufficiency, Renal tubular acidosis3, Ureteric colic, dysuria.

Eye disorders:

Very rare: Visual disturbance Ear and labyrinth disorders: Very rare: Tinnitus and vertigo Psychiatric disorders: Very rare: Nervousness General disorders and administration site conditions: Very rare: Peripheral oedema Investigations: Very rare: Decreased haematocrit and haemoglobin levels Description of Selected Adverse Reactions 1 Hypersensitivity reactions have been reported following treatment with ibuprofen.

These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm, dyspnoea or (c) assorted skin disorders, including rashes of various types pruritus, urticaria, purpura, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

2The pathogenic mechanism of drug-Induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation).

Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with ibuprofen, in patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

3Renal tubular acidosis and hypokalaemia have been reported in the post- marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

2 and GI and cardiovascular risks below). The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:

Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease. 5). 8) Aseptic meningitis: Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy.

Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

Renal:

Renal impairment as renal function may further deteriorate. 8). There is a risk of renal impairment in dehydrated children and adolescents. Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion.

In these patients, the administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly.

8). Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

8).

Cardiovascular and cerebrovascular effects:

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or mild to moderate heart failure as fluid retention; hypertension and oedema have been reported in association with NSAID therapy.

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). g. ≤1200mg/day) is associated with an increased risk of myocardial infarction.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.

g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) particularly if high doses of ibuprofen (2400 mg/day) are required. Cases of Kounis syndrome have been reported in patients treated with Ibuprofen Tablets. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.

Haematological effects:

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

Impaired female fertility:

There is limited evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. The use of ibuprofen therefore, 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. This is reversible upon withdrawal of treatment. 8). GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

3), and in the elderly. These patients should commence treatment on the lowest dose available. Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

5) When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Severe cutaneous adverse reactions (SCARs):

Severe […]

g. asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs. • Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

• History of gastrointestinal bleeding or perforation, relating to previous NSAIDs therapy. 6)