IBUPROFEN

4). Posology Adults, the elderly and children over 12 years: 200mg - 400mg, up to three times a day as required. To be taken preferably after food.

PL 33414/0085 Page 2 of 17 Children under 12 years of age:

Not recommended for children for children under the age of 12 years. 3 – Contraindications).

Hepatic impairment:

For patients with mild to moderate hepatic impairment (see section

). 8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products.

Ibuprofen should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity. In exceptional cases, varicella can be at the origin of serious cutaneous and soft tissues infectious complications.

To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of Ibuprofen in case of varicella. Masking of symptoms of underlying infections: ‘Migrafen 400 / Ebufac’ 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 ‘Migrafen 400 / Ebufac’ 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. PL 33414/0085 Page 6 of 17 Haematological effects Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and prolong bleeding time in normal subjects.

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.

Impaired female 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.

Excipients Iboprufen tablets contain sucrose and should not be given to patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

5 Interaction with other medicinal products and other forms of interaction Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.

Antihypertensives, beta-blockers and diuretics:

NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors, angiotensin-II receptor antagonists beta-blockers and diuretics. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides:

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Cholestyramine:

The concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.

Lithium:

Decreased elimination of lithium.

Methotrexate:

NSAIDs may inhibit the tubular secretion of methotrexate and reduce clearance of methotrexate.

Ciclosporin:

Increased risk of nephrotoxicity.

Mifepristone:

A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that coadministration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy.

4).

Aspirin (Acetylsalicylic acid):

As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects. Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly.

Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded.

1). 4). 4).

Quinolone antibiotics:

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Sulfonylureas:

NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen. 4).

Tacrolimus:

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine:

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent […]

3-Contraindications). 4). The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days. If in adolescents (between 12 and 18 years) this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

Leave at least four hours between doses and do not take more than 1200 mg in any 24 hour period. Method of administration For oral administration . It is recommended that patients with sensitive stomachs take Ibuprofen with food. To be taken preferably with or after food, with plenty of fluid.

Ibuprofen tablets should be swallowed whole and not chewed, broken, crushed or sucked on to avoid oral discomfort and throat irritation. 1. g. asthma, rhinitis, angioedema or urticaria) after taking ibuprofen, aspirin or other non-steroidal antiinflammatory drugs.

Ibuprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Ibuprofen should not be used in patients with active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding. 4). 6 ). 2, and GI and cardiovascular risks below). As with other NSAIDs, ibuprofen may mask the signs of infection. 5). The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of analgesic medication.

Patients with medication overuse headache should not be treated by increasing the dose of the analgesic. In such cases the use of analgesic should be discontinued. The concomitant consumption of excessive alcohol with NSAIDs, including ibuprofen may increase the risk of adverse effects on the gastrointestinal tract, such as GI haemorrhage or the central nervous system, possibly due to an additive effect.

2). Paediatric population There is a risk of renal impairment in dehydrated children and adolescents. Gastrointestinal bleeding, ulceration and perforation GI bleeding, ulceration or perforation, which can be fatal, have been reported for all NSAIDs at anytime 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. g. 5). PL 33414/0085 Page 4 of 17 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.

g. 5). When GI bleeding or ulceration occurs in patients receiving Ibuprofen, the treatment should be withdrawn. 8). Respiratory disorders and hypersensitivity reactions Caution is required if Ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma, chronic rhinitis or allergic diseases since NSAIDs have been reported to precipitate bronchospasm, urticaria or angioedema in such patients.

Cardiovascular, renal and hepatic impairment The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. The habitual concomitant intake of various similar painkillers further increases this risk.

Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. 3). Ibuprofen should be given with care to patients with a history of heart failure or hypertension […]

1. g. asthma, rhinitis, angioedema or urticaria) after taking ibuprofen, aspirin or other non-steroidal antiinflammatory drugs. Ibuprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Ibuprofen should not be used in patients with active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding). Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding.

4). 6 ). PL 33414/0085 Page 3 of 17