SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Flavamed Hustensaft 15 mg/5 ml oral solution 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 ml of oral solution contains 3 mg ambroxol hydrochloride. One measuring spoon with 5 ml of oral solution contains 15 mg ambroxol hydrochloride. Excipients with known effect Sorbitol 1.75 g/5 ml oral solution (see section 4.4 and 6.1) For the full list of excipients, see section PHARMACEUTICAL FORM Oral solution Clear, colourless to slightly brownish liquid with a fruity odour of raspberry 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Mucolytic therapy of productive cough associated with acute or chronic bronchopulmonary diseases Flavamed Hustensaft is indicated in children from two years, adolescents and adults. 4.2 Posology and method of administration Posology The following dosages are recommended for Flavamed Hustensaft: Children from 2 to 5 years: ½ a measuring spoon each with 2.5 ml oral solution is taken 3 times daily (equivalent to 22.5 mg ambroxol hydrochloride/day). Children from 6 to 12 years: 1 measuring spoon each with 5 ml oral solution is taken 2-3 times daily (equivalent to mg ambroxol hydrochloride/day). Adults and adolescents from 12 years: As a rule, 2 measuring spoons each with 5 ml oral solution are taken 3 times daily (equivalent to 90 mg ambroxol hydrochloride/day) during the first 2 to 3 days, then 2 measuring spoons each with 5 ml oral solution are taken 2 times daily (equivalent to 60 mg ambroxol hydrochloride/day). Note: The dose in adults can be increased up to 60 mg 2 times daily (equivalent to 120 mg ambroxol hydrochloride/day), where appropriate. See Section 4.4 for dosage in renal and hepatic diseases. - Page 1 of

2 Paediatric population See Section 4.3 for use in children under 2 years. See Section 4.4 for use in children from 2-4 years. Method and duration of administration Flavamed Hustensaft is for oral use. Flavamed Hustensaft is taken after meals with the aid of the measuring spoon. Flavamed Hustensaft should not be taken for longer than 4-5 days without the advice of a doctor. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Flavamed Hustensaft must not be used in children under two years. 4.4 Special warnings and precautions for use There have been reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP) associated with the administration of ambroxol. If symptoms or signs of a progressive skin rash (sometimes associated with blisters or mucosal lesions) are present, ambroxol treatment should be discontinued immediately and medical advice should be sought.because of a possible build-up of secretion, Flavamed Hustensaft should only be used with caution in disturbed bronchomotor function and large quantities of secretion (e.g. in the rare primary ciliary dyskinesia). Flavamed Hustensaft must only be used with particular caution (i.e. at longer intervals or at a reduced dose) in impaired renal function or a severe hepatic disease. In severe renal insufficiency, an accumulation of the metabolites of ambroxol formed in the liver must be expected. This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take Flavamed Hustensaft. Each measuring spoon with 5 ml of oral solution contains sorbitol 1.75 g (= 0.15 bread units). Sorbitol may have a mild laxative effect. The calorific value is 2.6 kcal/g sorbitol. Caution should be exercised in patients with histamine intolerance. Long-term therapy should be avoided in these patients, as ambroxol influences the histamine metabolism and may lead to symptoms of intolerance (e.g. headache, runny nose, itching). Since mucolytics may disrupt the gastric mucosal barrier ambroxol should be used with care in patients with a history of peptic ulcer disease. Paediatric population Persistent or recurrent cough in children beween 2-4 years requires medical diagnosis before treatment. 4.5 Interaction with other medicinal products and other forms of interaction On combined use of Flavamed Hustensaft with antitussives (cough-suppressant medicines), a dangerous build-up of secretion may develop due to the impaired cough reflex, meaning that the indication for this combination treatment should be examined particularly carefully. - Page 2 of

3 4.6 Fertility, pregnancy and lactation Pregnancy There are no sufficient data for the use of ambroxol in pregnant women. This particularly concerns the period up to the 28th week of pregnancy. Ambroxol has shown no teratogenic effects in animal-experiment studies (see Section 5.3). Flavamed Hustensaft should only be used in pregnancy after careful benefit/risk evaluation, particularly during the first trimester. Breast-feeding Ambroxol crosses into the breast milk in animals. As there is no adequate experience in humans to date, Flavamed Hustensaft should only be used in lactation after careful benefit/risk assessment. Fertility There are no sufficient data about the influence of ambroxol on fertility in humans. In animalexperiment studies, ambroxol showed no influence on fertility (see Section 5.3). 4.7 Effects on ability to drive and use machines There is no evidence for an effect on the ability to drive and use machines. Studies on the effects on the ability to drive and use machines have not been performed. 4.8 Undesirable effects The following frequencies are taken as a basis when evaluating undesirable effects: Very common: 1/10 Common: 1/100 to < 1/10 Uncommon: 1/1,000 to < 1/100 Rare: 1/10,000 to < 1/1,000 Very rare: < 1/10,000 Not known: Cannot be estimated from the available data Immune system disorders: Uncommon: Fever Rare: Hypersensitivity reactions Not known: Anaphylactic reactions including anaphylactic shock, angioedema and pruritus Nervous system disorders: Common: Dysgeusia (e.g. changed taste) Respiratory, thoracic and mediastinal disorders: Common: Oral and pharyngeal hypaesthesia Not known: Dry throat Gastrointestinal disorders Common: Nausea Uncommon: Vomiting, dry mouth, diarrhoea, dyspepsia and abdominal pain Skin and subcutaneous tissue disorders Rare: Rash, urticaria Not known: Severe cutaneous adverse reactions (including erythema multiforme, Stevens- Johnson syndrome/toxic epidermal necrolysis and acute generalized exanthematous pustulosis) - Page 3 of

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 listed in Appendix V 4.9 Overdose a) Symptoms of an overdose No specific overdose symptoms have been reported in man to date. Based on accidental overdose and/or medication error reports the observed symptoms are consistent with the known side effects of ambroxol at recommended doses and may need symptomatic treatment. b) Therapeutic measures in overdose Acute measures such as instituting vomiting and gastric lavage are not generally indicated and are to be considered only in extreme overdose. A symptomatic therapy is recommended. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Cough and cold preparations, Mucolytics ATC code: R05CB06 Ambroxol, a substituted benzylamine, is a metabolite of bromhexine. It differs from bromhexine by the absence of a methyl group and the introduction of a hydroxyl group in the para-trans position of the cyclohexyl ring. Although its mechanism of action has yet to be completely elucidated, mucolytic and secretomotor effects have been found in various investigations. Action following oral administration commences after 30 minutes on average and persists for 6-12 hours depending on the extent of the single dose. In preclinical investigations, it increases the proportion of serous bronchial secretion. The transport of mucus is thought to be promoted by the reduction of viscosity and the activation of the ciliated epithelium. Ambroxol induces activation of the surfactant system by acting directly on the type II pneumocytes of the alveoles and the Clara cells in the region of the small airways. It promotes the formation and outward transfer of surface-active material in the alveolar and bronchial region of the foetal and adult lungs. These effects have been demonstrated in cell cultures and in vivo on various species. Following use of ambroxol, concentrations of the antibiotics amoxicillin, cefuroxime, erythromycin and doxycycline in the sputum and in the bronchial secretion are increased. To date, it has not been possible to surmise a clinical relevance from this. 5.2 Pharmacokinetic properties Ambroxol is practically completely absorbed following oral administration. T max following oral administration is 1-3 hours. The absolute bioavailability of ambroxol on oral administration is reduced by approx. one third by a first-pass effect. Renally excreted metabolites (e.g. dibromo anthranilic acid, glucuronides) are formed in the process. Binding to plasma proteins is approx. 85 % (80-90 %). The terminal half-life in the plasma is 7-12 hours. The plasma halflife of the sum of ambroxol and its metabolites is approx. 22 hours. Ambroxol crosses the placental barrier and passes into the cerebrospinal fluid and breast milk. - Page 4 of

5 Excretion is 90 % renal in the form of metabolites formed in the liver. Unchanged ambroxol accounts for less than 10 % of renal excretion. Due to the high protein binding and the high volume of distribution, as well as the slow redistribution from the tissue to the blood, major elimination of ambroxol through dialysis or forced diuresis is not expected. Clearance of ambroxol is diminished by % in severe hepatic diseases. In severe renal dysfunction, an accumulation of the metabolites of ambroxol must be expected. 5.3 Preclinical safety data Preclinical data based on conventional studies on the safety pharmacology, investigations on the toxicity following acute and repeated administration, genotoxicity and carcinogenicity show no particular risk for humans. Investigations of reproductive toxicity on the rat and rabbit have produced no evidence of a teratogenic potential up to a dose of 3 g/kg body weight and 200 mg/kg body weight respectively. The peri- and postnatal development of rats was impaired only at a dose of 500 mg/kg. Fertility disturbances in rats were not observed at a dose of up to 1.5 g/kg. Ambroxol clears the placental barrier and crosses into breast milk in animals. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Sorbitol, liquid non-crystallising (E420) Benzoic acid Glycerol 85 per cent Hydroxyethylcellulose Raspberry flavouring Purified water 6.2 Incompatibilities Not applicable 6.3 Shelf life 3 years; after first opening of the bottle: 6 months 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Amber glass bottle (glass type III) with a screw cap, a tamper evident closure and a measuring spoon The screw cap is made from polypropylene. Colour concentrate white serves as colouring agent. A 5 ml measuring spoon with ¼ and ½ graduation is part of the product. The measuring spoon is made from polypropylene. Pack sizes: 1 x 60 ml of oral solution 1 x 100 ml of oral solution Not all pack sizes may be marketed. - Page 5 of

6 6.6 Special precautions for disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 7. MARKETING AUTHORISATION HOLDER 8. MARKETING AUTHORISATION NUMBER(S) 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10. DATE OF REVISION OF THE TEXT - Page 6 of