Carbocisteine 750mg/5ml sugar-free syrup

Oral solution. Clear, amber-coloured liquid, with raspberry odour.

4.1 Therapeutic indications Carbocisteine 750mg/5ml sugar-free syrup is indicated in adults and children over 15 years for the adjunctive therapy of respiratory tract disorders characterised by excessive, viscous mucus, including chronic obstructive airways disease.4.2 Posology and method of administration **Posology** For use in adults and children over 15 years of age only. **Adults** The recommended starting dose is 750mg carbocisteine three times a day which is 5ml three times a day (total 15ml/day). When symptoms improve, the daily dose may be reduced to 750mg twice a day which is 5ml two times a day (total 10ml/day). The maximum daily dose is 2250mg which is 15ml/day. **Elderly** **The same as the adult dosage.** ***Paediatric population*** Children over 15 years of age: The same as the adult dosage. Children under 15 years of age: Not recommended. **Method of administration** This medicine is for oral use. Use the measuring device to measure the appropriate amount. The measuring cup is graduated per 2.5 ml and 5 ml. Filling the measuring cup up to the graduation of 5 ml corresponds to 750 mg of carbocisteine. **Do not exceed the stated dose.** **A smaller volume of this product is needed, compared to other carbocisteine products, to achieve the same recommended dose.**4.3 Contraindications • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. •Active peptic ulceration.4.4 Special warnings and precautions for use **Special warning** This medicine contains sodium methyl para-hydroxybenzoate (E219) and may cause allergic reactions (possible delayed). This medicine contains 288.4 mg (12.53mmol) sodium per 15ml, equivalent to 14.4% of the WHO recommended maximum daily intake of the 2 g sodium for an adult. **Precautions for use** Caution is recommended in the elderly, in those with a history of gastroduodenal ulcers, or those taking concomitant medications known to cause gastrointestinal bleeding. Since mucolytics may disrupt the gastric mucosal barrier, caution should be taken in patients with a history of peptic ulcers. If gastrointestinal bleeding occurs, patients should discontinue medication.4.5 Interaction with other medicinal products and other forms of interaction The combination of mucolytics with antitussives and/or substances that dry out secretions (atropinic) is not recommended.4.6 Fertility, pregnancy and lactation **Pregnancy** There are no available data on carbocisteine use in pregnant women. No conclusions can be drawn regarding whether or not carbocisteine is safe for use during pregnancy. The use of carbocisteine in pregnant women is not recommended, especially during the first trimester. **Breast-feeding** There are no available data on the presence of carbocisteine in human milk, milk production, or the effects on the breastfed infant. No conclusions can be drawn regarding whether or not carbocisteine is safe for use during breastfeeding. The use of carbocisteine in breastfeeding women is not recommended. **Fertility** There are no fertility data available.4.7 Effects on ability to drive and use machines Carbocisteine 750mg/5ml sugar-free syrup has no or negligible influence on the ability to drive and use machines.4.8 Undesirable effects **Immune system disorders** There have been reports of anaphylactic reactions and fixed drug eruption. **Gastrointestinal disorders** There have been reports of diarrhoea, nausea, epigastric discomfort and gastrointestinal bleeding occurring during treatment with carbocisteine. *Frequency not known:* vomiting, gastrointestinal bleeding. **Skin and subcutaneous tissue disorders** There have been reports of skin rashes and allergic skin eruptions. Isolated cases of dermatitis bullous such as Stevens-Johnson syndrome and erythema multiforme have also been reported. **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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose Gastric lavage may be beneficial, followed by observation. Gastrointestinal disturbance is the most likely symptom of overdose. In such cases, it is advised to reduce the dosage.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: mucolytic, ATC code: R05CB03 Mechanism of action Carbocisteine (S-carboxymethyl L-cysteine) has been shown in normal and bronchitic animal models to affect the nature and amount of mucus glycoprotein which is secreted by the respiratory tract. Pharmacodynamic effects An increase in the acid: neutral glycoprotein ratio of the mucus and a transformation of serous cells to mucus cells is known to be the initial response to irritation and will normally be followed by hypersecretion. The administration of Carbocisteine to animals exposed to irritants indicates that the glycoprotein that is secreted remains normal; administration after exposure indicates that return to the normal state is accelerated. Clinical efficacy and safety Studies in humans have demonstrated that Carbocisteine reduces goblet cell hyperplasia. Carbocisteine can therefore be demonstrated to have a role in the management of disorders characterised by abnormal mucus.5.2 Pharmacokinetic properties Carbocisteine is rapidly asorbed from the GI tract. In an 'in-house' study, at steady state (7 days) carbocisteine capsusles 375mg given as 2 capsules t.d.s. to healthy volunteers gave the following pharmacokinetic parameters: | | | | | --- | --- | --- | | **Plasma Determinations** | **Mean** | **Range** | | **T Max (Hr)** | **2.0** | **1.0-3.0** | | **T**½ (Hr) | 1.87 | 1.4-2.5 | | KEL (Hr-1) | 0.387 | 0.28-0.50 | | AUG0.7.5 (mcg.Hr.m1-1) | 39.26 | 26.0-62.4 | **Derived Pharmacokinetic Parameters** | | | | --- | --- | | \*CLs (L.Hr-1) | 20.2 - | | CLs (ml.min-1) | 331 – | | VD (L) | 105.2 – | | VD (L.Kg-1) | 1/75 – | \*Calculated from dose for day 7 of study5.3 Preclinical safety data There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

6.1 List of excipients Glycerol Sodium Saccharin Hydroxyethylcellulose Xanthan gum Caramel powder Raspberry flavor Sodium Methyl Parahydroxybenzoate Sodium Hydroxide\* Purified water \* sodium hydroxide pellets or sodium hydroxide 30 % solution can be used6.2 Incompatibilities Not applicable.6.3 Shelf life 2 years. Once opened use within one month.6.4 Special precautions for storage Do not store above 25°C.6.5 Nature and contents of container 100ml & 200ml amber type III glass bottles with child resistant (HDPE) screw cap and a polypropylene measuring cup with 2.5 / 5 ml graduations.6.6 Special precautions for disposal and other handling No special requirements for disposal.