IBUPROFEN WELL PHARMACEUTICALS

For oral administration and short-term use only. 4). The patient should consult a doctor if the symptoms persist or worsen, or the product is required for more than 10 days.

Adolescents (age range: ≥ 12 years to < 18 years):

If this medicinal product is required for more than 3 days, or if symptoms persist or worsen, consult your doctor. Take one or two capsules with water to start with, repeat up to three times a day as required. Leave at least 4 hours between doses and do not take more than six capsules in any 24-hour period.

Not suitable for children under 12 years.

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200 mg ibuprofen per day), in short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.

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 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). System Organ Class Frequency Adverse Event Blood and Lymphatic System Disorders Very rare Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Uncommon Hypersensitivity reactions consisting of1:

Urticaria and pruritus Very rare Severe hypersensitivity reactions. Symptoms could be facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Immune System Disorders Not Known Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea.

Uncommon HeadacheNervous System Disorders Very rare Aseptic meningitis2 Cardiac Disorders Not Known Cardiac failure and oedema. Kounis syndrome. Vascular Disorders Not Known Hypertension Uncommon Abdominal pain, nausea, 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 Uncommon Various skin rashes Very rare Severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)).

Skin and Subcutaneous Tissue Disorders Not Known Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) Acute generalised exanthematous pustulosis (AGEP) Photosensitivity reactions Renal and Urinary Disorders Very rare Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Not Known Renal insufficiency, Renal tubular acidosis3, ureteric colic, dysuria. g. 4 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).

3*Renal 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. 4This is possibly associated with the mechanism of action of the non-steroidal anti-inflammatory drugs.

If signs of an infection occur or get worse during use of Ibuprofen the patient is therefore recommended to go to a doctor without delay. It is to be investigated whether there is an indication for anti-infective/antibiotic therapy.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see 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 history of, bronchial asthma or allergic disease. 8). 8) There is a risk of renal impairment in dehydrated children and adolescents. 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 heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

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

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. 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.

Impaired female fertility:

There is some evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment. 8). GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of 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 the 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. 8). Most of these reactions occurred within the first month. If signs and symptoms suggestive of these reactions appear ibuprofen should be withdrawn immediately and an alternative treatment considered (as appropriate).

Masking of symptoms of underlying infections Ibuprofen can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella.

When ibuprofen is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non- hospital settings, the patient should consult a doctor if symptoms persist or worsen.

Lactose intolerance:

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactase malabsorption should not take this medicine.

Intolerance to some sugars:

Patients with rare hereditary problems of galactose intolerance, fructose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

The label will include:

Read the enclosed leaflet before taking this product Do not take if you: • have (or […]

Hypersensitivity to ibuprofen or to any of the excipients. g. asthma, rhinitis, angioedema or urticaria), in response to ibuprofen, 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, related to previous NSAIDs therapy. 4). 6 Fertility, pregnancy and lactation). Children under 12 years.