BRUFENLIK 400 mg ibuprofen oral suspension in sachet - 20 sachets

Indicated for the short-term symptomatic treatment of mild-moderate pain and/or fever in adults and children over 6 years of age (> 20 kg).

Active Ingredients

Each sachet (10 ml) contains 200 mg ibuprofen. Each sachet (10 ml) contains 400 mg ibuprofen. Excipient(s) with known effect Each sachet (10 ml) contains 2500 mg maltitol (E 965), 20 mg sodium benzoate (E 211), 14 mg ethanol, 48 mg propylene glycol and 17 mg sodium. Each sachet (10 ml) contains 5000 mg maltitol (E 965), 10 mg sodium benzoate (E 211), 0.0017 mg benzyl alcohol and 58 mg sodium. For the full list of excipients, see section 6.1.

Excipients

Glycerol, Liquid Maltitol E965, Xanthan Gum, Citric Acid, Sodium Citrate, Sodium Benzoate E211, Sodium Saccharin, Purified Water. Only 200 mg : Microcrystalline Cellulose, Polysorbate 80, Orange Flavor containing Propylene Glycol and Ethanol. Only 400 mg: Sodium Chloride, Hypromellose, Strawberry Flavor containing Benzyl Alcohol, Thaumatin E957.

Dosage

Dosage Therapy should be started with the lowest effective dose, which may subsequently be adjusted, depending on the therapeutic response and any undesirable effects (see section 4.4). Adults and adolescents over 12 years of age ( ≥ 40 kg) The dose of ibuprofen depends on the age and body weight of the patient. The maximum single daily dose for adults and adolescents should not exceed 400 mg ibuprofen. More than 400 mg at a time does not provide a better analgesic effect. A total dose should not exceed 1,200 mg ibuprofen in 24 hours. Initial dose, 200 mg or 400 mg ibuprofen. If necessary, additional doses of 1 or 2 sachets (200 mg to 400 mg ibuprofen) may be taken up to 3-4 times daily at intervals of 4-6 hours. If this medicine is needed for more than 3 days in children and adolescents, or if symptoms worsen, a doctor should be consulted.

Paediatric population Children 6-12 years (20 kg-39 kg) The maximum total daily dose of ibuprofen is 30 mg per kg of body weight, divided into 3-4 single doses at intervals of 6-8 hours. The maximum recommended daily dose should not be exceeded.

Brufenlik 200 mg is not indicated for children under 6 years of age (<20 kg). Other more suitable ibuprofen formulations are available for this population. Elderly No specific dosage adjustment is necessary unless renal or hepatic function is impaired, in which case the dosage should be assessed individually. Caution should be exercised with dosing in this group. Renal impairment In patients with mild to moderate renal impairment, a dose reduction is not necessary (for patients with severe renal insufficiency, see section 4.3). Hepatic impairment In patients with mild to moderate hepatic impairment, a dose reduction is not necessary (for patients with severe hepatic dysfunction, see section 4.3) Method of administration For oral use. Mix the contents of the sachet well before swallowing by pressing the top and bottom of the sachet several times with the fingers. The contents of the sachet cannot be divided between doses and the entire contents of the sachet must be used. In order to achieve a faster onset of action, the dose may be taken on an empty stomach. Patients with gastric sensitivity problems are advised to take ibuprofen with food.

Warnings

General Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to achieve symptomatic control (see section 4.2, and gastrointestinal and cardiovascular effects listed below). Headache may occur during prolonged use of analgesics and should not be treated with higher doses of the medicinal product. Active substance-related undesirable effects, especially those involving the gastrointestinal tract or the central nervous system, may be increased during use of NSAIDs following concomitant alcohol consumption. Elderly Elderly patients are subject to an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal. Gastrointestinal bleeding, ulceration and perforation NSAIDs should be administered with caution to patients with a history of peptic ulceration and other gastrointestinal disease as these conditions may be exacerbated (see section 4.3). Gastrointestinal bleeding, ulceration or perforation have been reported with all NSAIDs at any time during treatment. These events can be fatal and may occur with or without warning symptoms or a history of serious GI events. 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 bleeding or perforation, and in the elderly. These patients should start treatment on the lowest dose available. Co-administration with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and for patients taking concomitant low dose aspirin/aspirin or other drugs likely to increase GI risk (see section 4.5). The concomitant administration of ibuprofen and other NSAIDs, including cyclooxygenase-2 (Cox-2) selective inhibitors, should be avoided due to the increased risk of ulceration or bleeding (see section 4.5). Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly in the initial stages of treatment. Caution should be exercised in treating patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet drugs such as acetylsalicylic acid/aspirin (see section 4.5). If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn. Respiratory disorders Caution should be exercised if ibuprofen is administered to patients with a previous or concomitant history of bronchial asthma, chronic rhinitis or allergic disease since NSAIDs have been reported to precipitate bronchospasm, urticaria or angioedema in these patients. Allergic reactions Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are observed very rarely. At the first signs of a hypersensitivity reaction following the intake/administration of ibuprofen, therapy should be discontinued. The required medical measures should be carried out by specialist personnel. Caution is necessary in patients who have had allergic or hypersensitivity reactions to other substances, since these patients may be at increased risk of hypersensitivity reactions following the intake of ibuprofen. There is an increased risk of allergic reactions in patients suffering from hay fever, nasal polyps or chronic obstructive respiratory diseases. Such reactions may present as asthma attacks (so-called analgesic asthma), Quincke's edema or urticaria. Impaired renal and hepatic function Caution is necessary in patients with renal, hepatic or cardiac impairment since the use of NSAIDs may cause deterioration of renal function. Habitual concomitant intake of similar analgesics further increases this risk. For patients with renal, hepatic or cardiac insufficiency, use the lowest effective dose for the shortest possible duration of treatment (see section 4.3). 400 mg sachets: see also section “Information on excipients (benzyl alcohol)”. Cardiovascular and cerebrovascular effects Caution is required (discuss with your doctor or pharmacist) before starting treatment in patients with a history of hypertension and/or heart failure, as fluid retention and oedema have been reported in association with NSAID therapy. Clinical trials suggest that use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a modest increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low doses of ibuprofen (e.g. ≤1200 mg/day) are 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. Careful consideration should also be exercised before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses (2400 mg/day) of ibuprofen are required. Serious skin reactions Serious skin reactions, some of them fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, eosinophilia and systemic symptoms (DRESS syndrome), have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions in the early stages of therapy, with the onset of the reaction occurring in most cases within the first month of treatment. Acute generalized exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing medicinal 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. Exceptionally, chickenpox may be the cause of serious infectious complications of the skin and soft tissue. At present, the active role of NSAIDs in the worsening of these infections cannot be excluded. Therefore, it is advisable to avoid the use of ibuprofen in case of chickenpox. Masking of symptoms of underlying infections Brufenlik may mask the symptoms of infection, which may delay the initiation of adequate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When Brufenlik is administered for the relief of infection-related fever or pain, monitoring for infection is advised. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen . Renal effects Caution should be exercised when initiating treatment with ibuprofen in patients with considerable dehydration. There is a risk of impaired renal function especially in dehydrated children and adolescents and in the elderly. As with other NSAIDs, prolonged administration of ibuprofen in animals has resulted in renal papillary necrosis and other pathological renal changes. Cases of renal toxicity have also been observed in patients in whom prostaglandins play a compensatory role in the maintenance of renal perfusion. In these patients, administration of NSAIDs may cause a dose-dependent reduction in prostaglandin production and, secondarily, in renal blood flow, which may result in renal failure. Patients most at risk of these reactions are those with impaired renal function, heart failure, liver dysfunction, the elderly and all patients taking diuretics and ACE inhibitors. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. Haematological effects Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and prolong bleeding time in normal subjects. Aseptic meningitis Aseptic meningitis has been observed on rare occasions in patients receiving ibuprofen. Although this is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been observed in patients without underlying chronic disease. Fertility There is evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility due to an effect on ovulation. This is reversible upon discontinuation of treatment (see section 4.6). Information on excipients 200 mg Ibuprofen 200 mg contains: • maltitol (E 965). Patients with rare hereditary problems of fructose intolerance should not take this medicine; • 20 mg sodium benzoate (E211) in each sachet equivalent to 2 mg/ml; • 17 mg sodium per 10 ml sachet, equivalent to 1% of the WHO recommended maximum daily intake of 2 g sodium for an adult; • orange flavour containing 14 mg alcohol (ethanol), in each 10 ml sachet. The amount in each sachet of this medicine is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will not produce any noticeable effects. • 48 mg propylene glycol in each sachet, equivalent to 4.8 mg/ml. 400 mg Ibuprofen 400 mg contains: • maltitol (E 965). Patients with rare hereditary problems of fructose intolerance should not take this medicine. • 10 mg sodium benzoate (E 211) in each sachet equivalent to 1 mg/ml; • 58 mg sodium per sachet, equivalent to 3% of the WHO recommended maximum daily intake of 2 g sodium for an adult. • Strawberry flavour containing 0.0017 mg benzyl alcohol in each 10 ml sachet. Benzyl alcohol may cause allergic reactions. Large volumes should be used with caution and only if necessary, especially in pregnant women and patients with hepatic or renal insufficiency due to the risk of accumulation and toxicity (metabolic acidosis). (See “Cardiac failure, renal and hepatic impairment” above and section 4.6).

Conservation

This medicinal product does not require any special storage conditions.

Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - In patients who have experienced asthma, urticaria or allergic reactions after taking acetylsalicylic acid or other NSAIDs; - Severe heart failure (NYHA class IV). - Severe hepatic insufficiency - Severe renal insufficiency (glomerular filtration rate less than 30 ml/min). - Disorders involving an increased tendency to bleeding or active bleeding. - History of gastrointestinal bleeding or perforation related to previous NSAID treatment. - Active gastric or duodenal ulcer or history of recurrent gastrointestinal ulcer/bleeding (two or more clear episodes of demonstrable ulceration or bleeding). During the last trimester of pregnancy.

Side effects

Adverse reactions possibly related to ibuprofen are listed below by frequency and MedDRA system organ class. Frequency groups are classified according to the following categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare ((≥1/10,000, <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data):

The adverse reactions observed with ibuprofen are generally common to other NSAIDs. Gastrointestinal disorders The most commonly observed adverse events are gastrointestinal in nature. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, gastrointestinal haemorrhage and exacerbation of colitis and Crohn's disease have been reported following the administration of ibuprofen (see section 4.3). Less frequently, gastritis, duodenal ulcer and gastric ulcer and gastrointestinal perforation have been observed. A transient burning sensation in the mouth or throat may occur with ibuprofen suspension or ibuprofen granules. Immune system disorders Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity including asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) various skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely, erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis). Infections and infestations Exacerbation of infection-related skin inflammation (e.g. development of necrotising fasciitis) has been described in conjunction with the use of NSAIDs. If signs of an infection appear or worsen during the use of ibuprofen, the patient should be advised to consult a doctor immediately. Skin and subcutaneous tissue disorders In exceptional cases, serious skin infections and soft tissue complications may occur in the course of varicella infection (see also “Infections and infestations” and section 4.4). Cardiac and vascular disorders Clinical trials suggest that use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a modest increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4). 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.

Overdose

Toxicity In children or adults, signs and symptoms of toxicity have generally not been observed at doses below 100 mg/kg. However, in some cases supportive treatment may be necessary. Children have been observed to show signs and symptoms of toxicity after ingestion of ibuprofen at doses of 400 mg/kg or more. In cases of severe poisoning, metabolic acidosis may occur. Symptoms Most patients who have ingested significant amounts of ibuprofen will experience symptoms within 4 to 6 hours. The most commonly reported symptoms of overdose include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, convulsions, and loss of consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnoea, CNS and respiratory depression have also been reported rarely. Cardiovascular toxicity including hypotension, bradycardia and tachycardia has been reported. Renal failure and liver damage may occur in cases of significant overdose. Significant overdoses are generally well tolerated provided no other medicinal products are involved. Treatment There is no specific antidote for ibuprofen overdose. Patients should be treated symptomatically as needed. Activated charcoal should be considered within one hour of ingestion of a potentially toxic amount. Serum electrolyte balance should be corrected if necessary. Contact your local poison control center for the most up-to-date information.

Pregnancy

Pregnancy Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo-foetal development. Data from epidemiological studies suggest an increased risk of miscarriage, cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has induced increased pre- and post-implantation loss and embryo-foetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenesis period. From the 20th week of pregnancy onwards, the use of ibuprofen may cause oligohydramnios resulting from fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible on discontinuation. In addition, cases of constriction of the ductus arteriosus have been reported following treatment in the second trimester, most of which resolved after discontinuation of treatment. Therefore, ibuprofen should not be given during the first and second trimester of pregnancy unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as low as possible. Antenatal monitoring for oligohydramnios and constriction of the ductus arteriosus should be considered after exposure to ibuprofen for several days from gestational week 20 onwards. Ibuprofen should be discontinued if oligohydramnios or constriction of the ductus arteriosus is observed. 400 mg sachets: Brufenlik 400 mg oral suspension in sachet also contains benzyl alcohol and, due to the risk of accumulation and toxicity (metabolic acidosis) associated with high volumes of benzyl alcohol, caution should be exercised in pregnant women. See also section 4.4 “Information on excipients (benzyl alcohol)”. In the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: - cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension), - renal dysfunction, which may progress to renal failure with oligohydramnios (see above); - At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate, at the end of pregnancy, to: - a possible prolongation of bleeding time, - an inhibition of uterine contractions, resulting in a delay or prolongation of labour. Consequently, ibuprofen is contraindicated during the third trimester of pregnancy. Breastfeeding 200 mg sachets : Ibuprofen is excreted in breast milk, but at therapeutic doses during short-term treatment the risk of influence on the infant seems unlikely. If, however, long-term treatment is prescribed, early weaning should be considered. 400 mg sachets: Ibuprofen is excreted in breast milk, but at therapeutic doses during short-term treatment the risk of influence on the infant seems unlikely. However, Brufenlik 400 mg oral suspension in sachet contains benzyl alcohol and, due to the risk of accumulation and toxicity (metabolic acidosis) associated with high volumes of benzyl alcohol, caution should be exercised in breast-feeding women (see also section 4.4 “Information on excipients (benzyl alcohol)”. However, if long-term treatment is prescribed, early weaning should be considered. 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, discontinuation of ibuprofen treatment should be considered (see section 4.4).