SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT (Invented name), film-coated tablet 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Paracetamol..............................................................................................................................500.00 mg Chlorphenamine maleate..............................................................................................................4.00 mg For one film-coated tablet Excipients with known effect: Carmoisine (E122) For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Oblong purple film-coated tablet. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications This medicinal product is indicated for treatment, during the course of colds, rhinitis, rhinopharyngitis and flu-like conditions in adults and children aged over 15 years: of clear nasal discharge and watering of the eyes, of sneezing, of headaches and/or fever. 4.2 Posology and method of administration Posology Restricted to adults and children over the age of 15 years. Weight Dose per Administration Maximum daily dose (age) administration interval Adults and 1 tablet 4 hours 4 tablets children >50 kg i.e., i.e., (>15 years) 500 mg of paracetamol 2,000 mg of paracetamol 4 mg of chlorphenamine 16 mg of chlorphenamine Do not exceed the maximum posology of 4 tablets per 24 hours. Patients with renal failure In the event of renal failure and unless otherwise medically advised, it is recommended that the dose be reduced and that the minimum interval between the 2 doses be increased, based on the following table: 2 Creatinine Administration interval clearance ≥50 ml/min 4 hours 10–50 ml/min 6 hours <10 ml/min 8 hours The total dose of paracetamol should not exceed 3 g/day. Patients with hepatic failure In patients with active or compensated chronic hepatic disease, particularly those with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), and dehydration, the dose of paracetamol should not exceed 3 g/day. Special clinical situations The lowest possible effective daily dose of paracetamol should be used, without exceeding 60 mg/kg/day (without exceeding 3 g/day) in the following conditions: adults weighing less than 50 kg, mild-to-moderate hepatocellular insufficiency, chronic alcoholism, chronic malnutrition, dehydration. Maximum recommended doses: in adults and children over 50 kg, THE TOTAL PARACETAMOL DOSE SHOULD NOT EXCEED 4 GRAMS PER DAY (see section 4.9). in adults and children over 50 kg, THE TOTAL DOSE OF CHLORPHENAMINE MALEATE SHOULD NOT EXCEED 16 MILLIGRAMS PER DAY (see section 4.9). Method of administration Oral use. The tablets should be swallowed as they are with a drink (e.g. water, milk, fruit juice). Evening doses should be favoured because of the sedative effect of chlorphenamine maleate. Frequency of administration 1 tablet, to be renewed if needed, after a minimum of 4 hours, without exceeding 4 tablets per day. Duration of treatment If fever or pain persist for more than 3 days, or symptoms fail to improve after 5 days of treatment, the management of treatment should be reassessed. 4.3 Contraindications Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. In children under 15 years of age. Due to the presence of paracetamol: Severe hepatocellular insufficiency or active decompensated hepatic disease. Due to the presence of chlorphenamine maleate: 3 Risk of angle-closure glaucoma. Risk of urinary retention related to urethroprostatic disorders. 4.4 Special warnings and precautions for use In case of high or persistent fever, or if signs of superinfection occur or symptoms persist for more than 5 days, treatment must be reassessed. In order to avoid a risk of overdose check that there is no paracetamol or chlorphenamine maleate in the composition of the other medicinal products (medicinal products obtained with or without a prescription), respect the maximum recommended doses (see section 4.2). This medicinal product contains an azo colouring agent (E122) and may cause allergic reactions. Related to the presence of paracetamol: Paracetamol should be used with caution in the event of: weight <50 kg, mild-to-moderate hepatocellular insufficiency, renal failure (see table in section 4.2), glucose-6-phosphate dehydrogenase (G6PD) deficiency (which may lead to haemolytic anaemia), chronic alcoholism, excessive alcohol consumption (3 or more alcoholic drinks per day), anorexia, bulimia or cachexia, chronic malnutrition (low reserves of hepatic glutathione), dehydration, hypovolaemia (see section 4.2). Very rare cases of serious skin reactions have been reported. Patients should be informed of the early signs of these serious skin reactions and the onset of a skin rash or any other signs of hypersensitivity leading to the discontinuation of treatment. Related to the presence of chlorphenamine maleate: This medicinal product should be used with caution in patients (particularly elderly patients) with: a higher sensitivity to orthostatic hypotension, vertigo, and sedation, chronic constipation (risk of paralytic ileus), possible prostatic hypertrophy, severe hepatic and/or renal failure, due to the risk of accumulation. Due to the presence of chlorphenamine, it is not recommended to take alcoholic drinks, medicinal products containing alcohol or sedatives (barbiturates in particular) during treatment, because they potentiate the sedative effect of antihistamines (see section 4.5). 4.5 Interaction with other medicinal products and other forms of interaction Related to the presence of paracetamol: Combinations requiring precautions for use + Antivitamin K Increased risk on the effect of antivitamin K and the risk of haemorrhage in the event that paracetamol is taken at maximum doses (4 g/day) for at least 4 days. 4 More frequent INR controls. Potential adjustment of the antivitamin K dosage during treatment with paracetamol and after its discontinuation. + Interactions with laboratory tests: Administration of paracetamol can cause errors in blood glucose tests using the glucose oxidase peroxidase method in the event of abnormally high concentrations. Administration of paracetamol can cause errors in blood uric acid assays using the phosphotungstic acid method. Related to the presence of chlorphenamine maleate: Combinations not recommended + Alcohol (drink or excipient) Increased sedative effect of H1 antihistamine by alcohol. Impaired alertness may make driving and use of machines dangerous. Avoid the consumption of alcoholic drinks and medicinal products containing alcohol. + Sodium oxybate Increased central nervous system depression. Impaired alertness may make driving and use of machines dangerous. Combinations to be taken into consideration + Other atropinic medicinal products: imipraminic antidepressants, most atropinic H1 antihistamines, anticholinergic antiparkinson agents, atropinic antispasmodics, disopyramide, phenothiazine neuroleptics and clozapine. Addition of atropinic undesirable effects such as urinary retention, constipation, dryness of the mouth. + Other sedative medicinal products: morphine derivatives (analgesics, antitussives and substitution treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines (meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1 antihistamines, centrally-acting antihypertensives; other: baclofen and thalidomide. Increased central nervous system depression. Impaired alertness may make driving and use of machines dangerous. 4.6 Fertility, pregnancy and lactation Pregnancy Studies in animals did not show evidence of a teratogenic or foetotoxic effect from paracetamol. Clinically, the results from epidemiology studies seem to rule out a specific malformation or foetotoxic effect from paracetamol or chlorphenamine. Prospective data on pregnant women exposed to paracetamol overdoses did not show an increased risk of malformation. Therefore, the use of this medicinal product during pregnancy and breast-feeding should only be considered if necessary. The recommended dosage and duration of treatment must be strictly respected. In the case of administration at the end of pregnancy, take into account the possible repercussions of the atropinic and sedative properties of chlorphenamine for newborns. 5 Breastfeeding It is not known whether chlorphenamine is excreted in breast milk. Given the possibilities of the newborn’s sedation or paradoxical excitation, this medicinal product is not recommended during breast- feeding. Fertility Due to a potential mechanism of action on cyclooxygenase and prostaglandin synthesis, paracetamol may alter fertility in women, by a reversible effect on ovulation upon discontinuation of treatment. Effects on male fertility have been observed in an animal study. The relevance of these effects in humans is unknown. 4.7 Effects on ability to drive and use machines (Invented name), film-coated tablet has a major influence on the ability to drive and use machines. Attention is drawn, particularly for drivers of vehicles and operators of machines, to the risks of sleepiness associated with the use of this medicinal product, especially at the beginning of treatment. This phenomenon is increased by the consumption of alcoholic drinks, or alcohol-containing medicinal products or sedative medicinal products. It is better to start this treatment in the evening. 4.8 Undesirable