Nurofen Cold and Flu 200mg + 30mg 12 coated tablets

INDICATIONS

NUROFEN FLU AND COLDS 200 mg + 30 mg Coated Tablets, is indicated in adults and adolescents over 12 years of age. Treatment of cold and flu symptoms such as nasal and sinus congestion, pain, fever, sore throat, headache.

ACTIVE INGREDIENTS

One tablet contains: Ibuprofen 200 mg, Pseudoephedrine hydrochloride 30 mg Excipients with known effects: sodium, sunset yellow FCF (E 110). For the full list of excipients, see section 6.1.

EXCIPIENTS

Tricalcium phosphate, sodium carboxymethylcellulose, microcrystalline cellulose, povidone, methylhydroxypropylcellulose, magnesium stearate, talc, colourants: E 104, E 110, E 171.

CONTRAINDICATIONS AND SIDE EFFECTS

Hypersensitivity to the active substances or to any of the excipients listed in paragraph 6.1. Patients suffering from peptic ulcer. History of gastrointestinal hemorrhage or perforation related to previous active treatments or history of recurrent hemorrhage/peptic ulcer (two or more distinct episodes of demonstrated ulceration or bleeding). Subjects who have previously shown hypersensitivity reactions (such as nasal polyposis, asthma, rhinitis, angioedema or urticaria) following the use of ibuprofen, acetylsalicylic acid or other analgesics, antipyretics, other non-steroidal anti-inflammatory drugs (NSAIDs). Severe kidney or liver failure. Severe heart failure (NYHA class IV) Patients with serious cardiovascular diseases, tachycardia, hypertension, angina pectoris, hyperthyroidism, diabetes, pheochromocytoma, glaucoma, prostatic syndrome. Pregnancy. Breastfeeding (see section 4.6). Children under 12 years old. Patients taking or have taken monoamine oxidase inhibitors (MAOIs) in the previous 14 days (see section 4.5).

DOSAGE

Dosage Only for a short period of treatment. • maximum 5 days of therapy for the adult population; • 3 days maximum therapy for the pediatric population (12-18 years). Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see section 4.4). If the use of the medicine is necessary for more than 5 days in adults and for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted. Pediatric population: Do not administer to children under 12 years of age Adults and adolescents over 12 years old: The initial dose is 1-2 tablets per day, then, if necessary, 1-2 tablets every 4 hours. Do not exceed the dose of 6 tablets in 24 hours. Elderly: No changes to the recommended dosage are required in the elderly except in patients with renal or hepatic alterations for whom it is necessary to individually adapt the dosage. Method of administration: Oral use.

CONSERVATION

This medicinal product does not require any special storage conditions.

WARNINGS

Side effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the sections below on Gastrointestinal and Cardiovascular Risks). Other NSAIDs: the use of NUROFEN COLD AND FLU should be avoided in conjunction with NSAIDs, including selective COX-2 inhibitors. Avoid the simultaneous use of two or more analgesics, antipyretics, non-steroidal anti-inflammatory drugs, as this leads to an increased risk of side effects. The use of NSAIDs must be carefully evaluated in patients suffering from coagulation disorders as a reduction in coagulability is possible. The same applies to patients being treated with oral anticoagulants, due to the possibility of an enhancement of the anticoagulant effect (see also section 4.5). Gastrointestinal safety: as with all anti-inflammatories, the drug should not be taken if the patient suffers from ulcers or gastric disorders. Gastrointestinal haemorrhage, ulceration and perforation: Gastrointestinal haemorrhage, ulceration and perforation, which may be fatal, have been reported at any time during treatment with all NSAIDs, with or without warning symptoms or previous history of serious gastrointestinal events. 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. The concomitant use of protective agents (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 below). 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 exercised in patients taking concomitant medications that may increase the risk of ulceration or haemorrhage, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5). When gastrointestinal bleeding or ulceration occurs in patients taking NUROFEN FLU AND COLDS, treatment should be discontinued. 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). Cardiovascular and cerebrovascular effects: caution is required (discuss with your doctor or pharmacist) before starting treatment in patients with a positive history of hypertension and/or heart failure since fluid retention, hypertension and edema have been found in association with treatment with NSAIDs. 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). In general, 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 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. Be careful consideration must also be exercised before starting long-term treatment for patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking habit), especially if high doses (2400 mg/day) of ibuprofen are necessary. 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). In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases in the early stages of treatment. NUROFEN FLU AND COLDS should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Severe skin reactions: Severe skin reactions, such as acute generalized exanthematous pustulosis (PEAG), may occur with medicines containing ibuprofen and pseudoephedrine. This acute pustular eruption may occur within the first 2 days of treatment, with fever and numerous, small, mostly non-follicular pustules resulting from a widespread edematous erythema and localized mainly on the skin folds, trunk and upper limbs. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema or numerous small pustules are observed, the administration of Nurofen Flu and Cold should be stopped and appropriate measures taken if necessary. Respiratory disorders: bronchospasm may occur in patients with bronchial asthma or current or previous allergic diseases. Do not take the product in cases of asthma and allergy to acetylsalicylic acid unless after consulting your doctor (see paragraph 4.3). SLE and mixed connective tissue disease: in case of systemic lupus erythematosus and mixed connective tissue disease it may lead to an increased risk of aseptic meningitis (see section 4.8). Renal function: renal failure, as renal function may be impaired (see sections 4.3 and 4.8). Liver function: liver dysfunction (see sections 4.3 and 4.8). Impaired female fertility: see paragraph 4.6 regarding female fertility. To be used with caution in combination with antihypertensives including neuronal adrenergic blockers and beta blockers (see section 4.5). To be used with caution with other sympathomimetic agents such as decongestants, appetite suppressants and amphetamine psycho-stimulants (see section 4.5). To be used with caution in case of hyperexcitation. If hallucinations, restlessness or sleep disturbances occur during administration of the medicine, use of the medicine should be discontinued. Elderly: Elderly patients present a higher frequency of adverse reactions to NSAIDs, in particular gastrointestinal haemorrhage and perforation which can be fatal (see section 4.2). Pediatric population: In dehydrated adolescents there is a risk of impaired renal function. Ischemic colitis: Some cases of ischemic colitis have been reported with pseudoephedrine. If sudden abdominal pain, rectal bleeding, or other symptoms of ischemic colitis develop, pseudoephedrine should be discontinued and a physician should be consulted. Ischemic optic neuropathy Cases of ischemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or reduction in visual acuity occurs, for example in the case of a scotoma. Masking of symptoms of underlying infections Nurofen Flu and Cold can mask the symptoms of infection, which could delay starting 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 Nurofen Flu and Cold is administered for the relief of fever or pain related to infection, monitoring of the infection is recommended. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. This medicinal product contains: • less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”; • sunset yellow dye FCF (E 110), which can cause allergic reactions.

INTERACTIONS

Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal haemorrhage (see section 4.4). Corticosteroids: increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4). The product must not be taken by patients being treated with monoamine oxidase inhibitors and for 14 days following the cessation of such treatment. The product may enhance the effect of other sympathomimetic agents, such as decongestants. The effect of pseudoephedrine could be reduced by guanethidine, reserpine and methyldopa and could be influenced by tricyclic antidepressants. In turn, pseudoephedrine may reduce the effect of guanethidine and may increase the possibility of arrhythmias in digitized patients, or in patients taking anticholinergics (including tricyclic antidepressants) or quinidine. 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 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. These interactions should be considered in patients taking NUROFEN FLU AND COLDS concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy. Acetylsalicylic acid: concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects (see section 4.4). Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the 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 use of two or more NSAIDs should be avoided as it may increase the risk of adverse events (see section 4.4). Cardiac glucosides: NSAIDs can worsen heart failure, reduce GFR (glomerular filtration rate) and plasma levels of glucosides. Lithium. There is evidence of the possibility of a potential increase in lithium levels in the blood. Methotrexate. There is evidence of the possibility of an increase in plasma levels of methotrexate. Cyclosporins: increase the risk of nephrotoxicity. Mifepristone: NSAIDs cannot be administered for 8-12 days following administration of mifepristone as NSAIDs may reduce the effect of mifepristone. Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are administered with tacrolimus. Zidovudine: Increased risk of hematological toxicity when NSAIDs are used concomitantly with Zidovudine. There is evidence of increased risk of hemarthrosis and hematoma in HIV-positive haemophilia patients if treated simultaneously with zidovudine and ibuprofen. Quinolone antibiotics: Data from animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures. Ergot alkaloids (ergotamine and methysergide): increased risk of ergotism. Appetite suppressants (anorectics) and amphetamine-like psychostimulants: risk of hypertension. Oxytocin: risk of hypertension

SIDE EFFECTS

The list of the following side effects includes those that have been observed during treatment with ibuprofen at self-medication doses (up to a maximum of 1200mg per day) and with sympathomimetics including pseudoephedrine for short periods of administration. Side effects associated with the administration of ibuprofen and sympathomimetics such as pseudoephedrine are listed below according to system organ class and frequency. For the frequency of occurrence of side effects, the following expressions are used: Very common (≥ 1/10) Municipality ( _≥ 1/100, <1/10) Uncommon ( _≥ 1/1000, <1/100) Rare ( _≥ 1/10.000, <1/1000) Very rare (<1/10,000) Not known (frequency cannot be estimated from the available data) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table of side effects

Blood and lymphatic system disorders - Frequency: Uncommon. Adverse Reaction: Hypersensitivity reactions characterized by urticaria and pruritus²

Blood and lymphatic system disorders - Frequency: Very rare. Adverse Reaction: Hematopoietic disorders¹. Severe hypersensitivity reactions. Symptoms may be: swelling of the face, tongue and larynx, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).²

Psychiatric disorders - Frequency: Not known. Adverse Reaction: Insomnia, anxiety, restlessness, agitation, hallucinations.

Nervous system disorders - Frequency: Uncommon. Adverse Reaction: Headache, tremors.

Nervous system disorders - Frequency: Very rare. Adverse Reaction: Aseptic meningitis³

Eye disorders - Frequency: Not known. Adverse Reaction: Ischemic optic neuropathy.

Cardiac disorders - Frequency: Not known. Adverse Reaction: Heart failure and edema4, tachycardia, chest pain, arrhythmia, palpitations.

Vascular disorders - Frequency: Not known. Adverse Reaction: Hypertension4.

Respiratory, thoracic and mediastinal disorders - Frequency: Not known. Adverse Reaction: Reactivity of the respiratory system including asthma, bronchospasm or dyspnoea²

Gastrointestinal disorders - Frequency: Uncommon. Adverse Reaction: Abdominal pain, nausea and dyspepsia5.

Gastrointestinal disorders - Frequency: Rare. Adverse Reaction: Diarrhoea, flatulence, constipation and vomiting.

Gastrointestinal disorders - Frequency: Very rare. Adverse Reaction: Peptic ulcer, gastrointestinal perforation or haemorrhage, melena, haematemesis, sometimes fatal, particularly in the elderly (see section 4.4). Ulcerative stomatitis, mouth ulcerations, gastritis.

Gastrointestinal disorders - Frequency: Not known. Adverse Reaction: Dry mouth. Exacerbation of colitis and Crohn's disease (see section 4.4). Ischemic colitis.

Hepatobiliary disorders - Frequency: Very rare. Adverse Reaction: Liver disorders.

Skin and subcutaneous tissue disorders - Frequency: Uncommon. Adverse Reaction: Skin rashes ²

Skin and subcutaneous tissue disorders - Frequency: Very rare. Adverse Reaction: Bullous reactions including Stevens-Johnson syndrome, erythema multiforme and Toxic Epidermal Necrolysis may occur.

Skin and subcutaneous tissue disorders - Frequency: Not known. Adverse Reaction: Hyperhidrosis. Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Severe skin reactions, including acute generalized exanthematous pustulosis (PEAG). Photosensitivity reactions

Musculoskeletal system and connective tissue disorders - Frequency: Not known. Adverse Reaction: Muscle weakness.

Renal and urinary disorders - Frequency: Very rare. Adverse Reaction: Severe renal failure 6.

Renal and urinary disorders - Frequency: Not known. Adverse Reaction: Urinary retention.

General disorders and conditions relating to the administration site - Frequency: Not known. Adverse Reaction: Irritability, thirst.

Diagnostic tests - Frequency: Very rare. Adverse Reaction: Decreased hemoglobin level in the blood.

Description of some side effects 1) Examples of hematopoietic disorders include anemia, leukopenia, thrombocytopenia, pancytopenia, and agranulocytosis. The first symptoms are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe feeling of tiredness, unexplained bleeding and bruising. 2) Hypersensitivity reactions: these reactions include a) non-specific allergic reactions and anaphylaxis, b) respiratory tract reactivity including asthma, worsening of asthma, bronchospasm or dyspnoea or c) various skin conditions such as various skin rashes, pruritus, urticaria, purpura, angioedema and very rarely bullous and exfoliative dermatitis including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme, d) cross-reactivity reactions with pseudoephedrine 3) The pathogenesis of drug-induced aseptic meningitis is not completely known. However, the data available on aseptic meningitis related to the administration of NSAIDs leads us to think of an immune hypersensitivity reaction (due to a temporary relationship with the intake of the medicine and the disappearance of symptoms after discontinuation of treatment). Of note, individual cases of aseptic meningitis symptoms (such as stiff neck, headache, nausea, vomiting, fever and disorientation) have been observed during treatment with ibuprofen in patients with autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease). 4) 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) 5) Gastrointestinal: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). 6) Especially during long treatments, associated with an increase in serum urea and edema. Also includes papillary necrosis. Gastrointestinal intolerance, bleeding, sweating, dizziness, precordial pain, difficulty urinating and insomnia may occur. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous 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-reazioniavverse.

OVERDOSE

Symptoms Nausea, vomiting, abdominal pain and more rarely diarrhea may occur. Tinnitus, headaches and gastrointestinal bleeding may also occur. In more severe cases of poisoning, central nervous system toxicity is observed, manifested by dizziness, drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop seizures. In cases of severe poisoning, metabolic acidosis and a prolongation of the prothrombin time/INR may occur, probably caused by interference with the action of coagulation factors present in the circulation. Acute renal failure, liver damage and respiratory depression may also occur. In asthmatic subjects, asthma exacerbation may occur. As with other sympathomimetics, an excessive dose of pseudoephedrine can cause symptoms related to central nervous system disorders and cardiovascular stimulation, including: irritability, restlessness, tremors, thirst, blurred vision, anxiety anxiety, insomnia, fever, sweating, exophthalmos, hallucinations, muscle weakness, palpitations, convulsions, urinary retention, hypertension, difficulty urinating, nausea, vomiting, tachycardia and cardiac arrhythmias. Treatment Treatment must be symptomatic and supportive, particularly of the cardiovascular and respiratory systems, and must include maintaining a patent airway and monitoring cardiac function and vital signs until the patient is stabilized. Oral administration of activated charcoal should be considered if the patient presents within 1 hour of ingesting a potentially toxic quantity. If necessary, corrective intervention of serum electrolytes should be used. Seizures should be treated with intravenous benzodiazepines if they are frequent or prolonged. Administer bronchodilators in case of asthma. The elimination of pseudoephedrine can be accelerated by acid diuresis or dialysis. Hypertensive phenomena can be treated with IV alpha receptor blocking drugs. Cardiac arrhythmias may require the use of beta-adrenergic blocking agents after administration of alpha-adrenergic blockers. Hyperexcitability and hallucinations can be treated with chlorpromazine.

PREGNANCY AND BREASTFEEDING

The product should not be used during pregnancy and breastfeeding. Pregnancy: Inhibition of prostaglandin synthesis can negatively affect pregnancy and/or embryo/foetal development. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in the early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was thought to increase with the dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-foetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals to which prostaglandin synthesis inhibitors were administered during the organogenetic period. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can expose the fetus to: - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); - renal dysfunction which may progress to renal failure with oligo-hydramnios; The mother and newborn, at the end of pregnancy, are exposed to: - possible prolongation of bleeding time, an anti-aggregating effect which can occur even at very low doses; - inhibition of uterine contractions resulting in delayed or prolonged labor. There is the possibility of an association between the onset of fetal anomalies and taking pseudoephedrine in the first trimester of pregnancy. Breastfeeding: Although ibuprofen is present in breast milk in very low concentrations, pseudoephedrine is secreted into milk in significant quantities; for this reason the product must not be used during breastfeeding. Fertility: As with other NSAIDs, the use of NUROFEN FLU AND COLDS can alter female fertility due to its effect on ovulation. It is therefore not recommended in women wishing to conceive.

EFFECTS ON DRIVING ABILITY

Not applicable