Nurofencaps 400mg 10 soft capsules

In compliance with article 118 "authorization of advertising to the public" of the legislative decree of 24 April 2006, number 219

INDICATIONS

This medicine is indicated in adults, children and adolescents weighing more than 40 kg (from 12 years of age) for the short-term symptomatic treatment of mild to moderate pain, such as headache, menstrual pain, toothache and pain associated with the common cold.

CONTRAINDICATIONS

• Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1. • Patients who have experienced hypersensitivity reactions (such as bronchospasm, asthma, rhinitis, angioedema or urticaria) associated with the use of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory products (NSAIDs). • History of gastrointestinal bleeding or perforation related to previous NSAID treatment • Patients with current peptic ulcer/haemorrhage or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding). • Patients with severe hepatic, renal or cardiac insufficiency (NYHA Class IV). See also section 4.4 • Patients with cerebrovascular bleeding or other active bleeding. • Patients with unclear hematopoiesis disorders. • Patients with severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake) • During the last trimester of pregnancy (see section 4.6). • Adolescents weighing less than 40 kg or children under 12 years of age.

WARNINGS AND PRECAUTIONS FOR USE

Side effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see below for gastrointestinal and cardiovascular risks). Caution is required in patients with the following conditions, which may worsen: • systemic lupus erythematosus and mixed connective tissue disease - for increased risk of aseptic meningitis (see section 4.8) • congenital disorders of porphyrin metabolism (e.g. Acute Intermittent Porphyria) • gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease (see section 4.8) • hypertension and/or heart failure (see sections 4.3 and 4.8) • renal failure, as renal function may be impaired (see sections 4.3 and 4.8) • liver dysfunction (see sections 4.3 and 4.8) • immediately after major surgery • In patients who experience allergic reactions to other substances, as they are at higher risk of developing hypersensitivity reactions even when using Nurofencaps • In patients suffering from hay fever, nasal polyps, respiratory disorders chronic obstructive disorders, or who have a history of allergic diseases, as there is an increased risk for these patients of developing allergic reactions. These can manifest themselves in the form of asthma attacks (so-called "analgesic asthma"), Quincke's edema or urticaria. Masking of symptoms of underlying infections Nurofencaps may mask the symptoms of infection, which could delay the initiation of appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Nurofencaps is administered for the relief of fever or pain related to infection, monitoring of the infection is advised. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. Gastrointestinal (GI) safety: Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions (see section 4.5) and should be avoided. Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2). Gastrointestinal haemorrhage, ulceration and perforation: Gastrointestinal haemorrhage, ulceration and perforation, which may be fatal, have been reported during treatment with all NSAIDs at any time, with or without warning symptoms or previous history of serious gastrointestinal events. When gastrointestinal bleeding or ulceration occurs following administration of ibuprofen, treatment should be discontinued. In the elderly and in patients with a history of ulcer, especially if complicated by haemorrhage or perforation (see section 4.3), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see section 4.5). Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly in the initial stages of treatment. Caution should be advised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs) or antiplatelet agents such as acetylsalicylic acid (see section 4.5). NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8). Severe skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at higher risk in the early stages of therapy: the onset of the reaction occurs in most cases within the first month of treatment. Acute generalized exanthematous pustulosis (PEAG) has been reported in connection with ibuprofen-containing medicinal products. Nurofencaps should be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as rash, mucosal lesions or any other sign of hypersensitivity. Chickenpox can exceptionally cause serious infectious complications to the skin and soft tissues. It is advisable to avoid using Nurofencaps in case of chickenpox. Cardiovascular and cerebrovascular effects: Before starting treatment in patients with a history of hypertension and/or heart failure, caution is required (consult your doctor or pharmacist) since fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). In general, epidemiological studies do not suggest that low doses of ibuprofen (e.g. ≤1200 mg per day) are associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration and high doses (2400 mg/day) should be avoided. Careful consideration must also be exercised before starting patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking habit) on long-term treatment, especially if high doses (2400 mg/day) of ibuprofen are necessary. Other considerations Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are observed very rarely. At the first signs of hypersensitivity reaction after administration/taking of Nurofencaps, therapy should be discontinued. The medical aid measures required based on the symptoms must be undertaken by specialized personnel. Ibuprofen, the active ingredient in Nurofencaps, can temporarily inhibit the function of platelets (thrombocyte aggregation), therefore it is recommended to carefully monitor patients with coagulation disorders. In case of prolonged administration of Nurofencaps, regular monitoring of liver values, renal function and blood counts is required. Prolonged use of any type of pain reliever for headaches can worsen symptoms. If this situation occurs or is suspected, the doctor should be consulted and treatment should be suspended. The diagnosis of headache due to medication abuse (medication overuse headache -MOH) should be suspected in patients who experience frequent or daily headaches despite or because of regular use of headache medications. The habitual use of analgesics, especially combinations of different analgesic active ingredients, can lead to permanent kidney damage with the risk of onset of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration. Side effects related to the active ingredient, in particular those relating to the gastrointestinal tract or central nervous system, may be increased by taking NSAIDs in combination with alcohol. There is some evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility through effect on ovulation. This effect is reversible after discontinuation of treatment. (see section 4.6). In dehydrated children and adolescents there is a risk of impaired kidney function. This medicine contains sorbitol: Patients suffering from rare hereditary problems of fructose intolerance should not take this medicine. This medicine contains Ponceau 4R (E124). May cause allergic reactions.

INTERACTIONS

Acetylsalicylic acid (low dose). Concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects. Experimental data suggest that ibuprofen can competitively inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when the two drugs are administered simultaneously. Although there are uncertainties regarding the extrapolation of these data to the clinical situation, the possibility cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of acetylsalicylic acid at low doses. No relevant clinical effects are considered likely following occasional use of ibuprofen (see section 5.1). Other NSAIDs including selective cyclooxygenase-2 inhibitors. Concomitant administration of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to the synergistic effect. The concomitant use of ibuprofen with other NSAIDs should therefore be avoided (see section 4.4) Digoxin. Phenytoin, Lithium. The simultaneous use of Nurofencaps with digoxin, phenytoin or lithium. may increase serum levels of these medicines. With correct use (maximum for 4 days) it is not usually necessary to control the levels of lithium, dioxin, phenytoin in the serum. Corticosteroids. Corticosteroids may increase the risk of adverse reactions, especially of the gastrointestinal tract (gastrointestinal ulceration or haemorrhage) (see section 4.3) Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4). Anticoagulants. NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4) Probenecid and sulfinpyrazone. Medicines containing probenecid or sulfinpyrazone may delay the excretion of ibuprofen Diuretics, ACE inhibitors and Angiotensin II antagonists. NSAIDs can reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) co-administration of an ACE inhibitor, a beta-blocker or an angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy, and periodically thereafter Potassium-sparing diuretics. Co-administration of Nurofencaps and potassium-sparing diuretics may cause hyperkalemia. Methotrexate. Administration of Nurofencaps in the 24 hours before and after the administration of methotrexate may lead to an increase in plasma levels of methotrexate and an increase in its toxic effects. Cyclosporine. Coadministration with some nonsteroidal anti-inflammatory drugs increases the risk of liver injury from cyclosporine. This effect cannot also be excluded for the association of ciclosporin with ibuprofen. Tacrolimus. the risk of nephrotoxicity increases if the two medicines are administered simultaneously. Zidovudine. There is evidence of an increased risk of haemarthrosis and haematoma in HIV-positive haemophilia patients if treated simultaneously with zidovudine and ibuprofen. There is a risk of increased haematological toxicity when NSAIDs are administered with zidovudine. Sulfonylureas Clinical investigations have highlighted interactions between non-steroidal anti-inflammatory drugs and anti-diabetics (Sulfonylureas). Although no interactions between antidiabetics and ibuprofen have been described so far, it is recommended to monitor plasma glucose levels as a precaution in case of co-administration. Quinolone antibiotics Experimental animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of having seizures. Mifepristone: NSAIDs should not be used for 8-12 days after administration of Mifepristone as NSAIDs may reduce the effect of Mifepristone. CYP2C9 inhibitors: Concomitant administration of ibuprofen and CYP2C9 inhibitors may potentiate exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), increased exposure to S(+)-ibuprofen by approximately 80% to 100% was observed. Ibuprofen dose reduction should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with voriconazole and fluconazole.

SIDE EFFECTS

The list of the following side effects includes all side effects that have been recognized during treatment with ibuprofen, even those observed during prolonged high-dose therapy in patients with rheumatism. The frequencies reported, which extend beyond reports of very rare side effects, refer to short periods of treatment for daily doses up to a maximum of 1200 mg of ibuprofen for oral pharmaceutical forms and up to a maximum of 1800 mg for suppositories. It should be taken into account that the following adverse reactions are predominantly dose-dependent and vary from individual to individual. The most commonly observed adverse reactions are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of ibuprofen (see section 4.4). Less frequently, gastritis was observed. In particular, the risk of gastrointestinal bleeding depends on the dosage and duration of treatment. Edema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg/day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). Hypersensitivity reactions have been reported and may manifest as: (a) non-specific allergic reactions and anaphylaxis; (b) respiratory tract reactivity, such as asthma, aggravated asthma, bronchospasm, dyspnea; (c) various skin reactions, such as pruritus, urticaria, angioedema and more rarely bullous and exfoliative dermatoses (including epidermal necrolysis and erythema multiforme). The patient should be informed to immediately inform the doctor and stop taking Nurofencaps if any of the above-mentioned adverse reactions occur. Please note that for each frequency group, side effects are presented in order of decreasing seriousness:

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)

Not known (frequency cannot be estimated from the available data)

Infections and infestations. Very rare: Exacerbation of infection-related inflammation (e.g. development of necrotizing fasciitis) has been described with the use of non-steroidal anti-inflammatory drugs. This is potentially associated with the mechanism of action of nonsteroidal anti-inflammatory drugs. If signs of infection appear or worsen while using Nurofencaps, the patient is recommended to contact a doctor immediately. The possible indication for anti-infective/antibiotic therapy must be evaluated. Symptoms of aseptic meningitis such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed during treatment with ibuprofen. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue disease) appear to be predisposed. Pathologies of the blood and lymphatic system. Very rare: haematopoietic disorders (anaemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first manifestations may be: fever, sore throat, superficial ulcers of the oral cavity, flu-like symptoms, severe fatigue, nasal and skin bleeding. In these cases the patient must be informed to immediately suspend therapy, to avoid taking any analgesic or antipyretic self-medication medicines and to consult the doctor. For prolonged therapy the blood count must be checked regularly. Immune system disorders (hypersensitivity). Uncommon: hypersensitivity reactions with urticaria and itching, as well as asthma attacks (possibly with fall in blood pressure). Very rare: severe generalized hypersensitivity reactions. Symptoms may be: swelling of the face, tongue and larynx, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Exacerbation of asthma and bronchospasm. Psychiatric disorders. Very rare: psychotic reactions, depression. Nervous system disorders. Uncommon: central nervous system disorders such as headache, dizziness, drowsiness, agitation, irritability or tiredness. Eye pathologies. Uncommon: visual disturbances. Ear and labyrinth disorders. Rare: tinnitus, hearing impairment. Cardiac diseases. Very rare: palpitations, heart failure, myocardial infarction. Vascular pathologies. Very rare: arterial hypertension, vasculitis. Gastrointestinal disorders. Common: gastrointestinal disorders such as dyspepsia, heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation and slight gastrointestinal blood loss which in exceptional cases can cause anemia; Uncommon: Gastrointestinal ulcers, potentially with perforation and gastrointestinal bleeding. Ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4), gastritis; Very rare: esophagitis, pancreatitis, formation of diaphragmatic-like intestinal strictures. The patient should be advised to discontinue the medicinal product and seek immediate medical attention if severe upper abdominal pain, melena or haematemesis occurs. Hepatobiliary disorders. Very rare: liver dysfunction, liver damage, especially following long-term treatment, liver failure, acute hepatitis. Pathologies of the skin and subcutaneous tissue. Uncommon: various skin rashes; Very rare: bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), alopecia. In exceptional cases, serious skin infections and soft tissue complications may occur during a chickenpox infection (see also “Infections and infestations”). Not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acute generalized exanthematous pustulosis (PEAG). Photosensitivity reactions. Renal and urinary disorders. Rare: Kidney tissue damage (papillary necrosis) and high concentrations of uric acid in the blood may rarely occur. High concentrations of urea in the blood; Very rare: edema formation, particularly in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis which may be accompanied by acute renal failure. Kidney function should therefore be checked regularly. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Diagnostic tests. Rare: decreased hemoglobin levels.