CARBOCISTEINE 750 MG / 5ML SUGAR-FREE SYRUP - summary of medicine characteristics

Carbocisteine 750mg/5ml sugar-free syrup

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5ml of oral solution contains 750mg of carbocisteine.

Excipient with known effect

Each 5ml of oral solution contain 96.1mg (4.2mmol) of sodium.

Each 5ml of oral solution contain 7.5mg of sodium methyl parahydroxyben­zoate.

For the full list of excipients, see section 6.1.

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

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 study

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

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 used

6.2 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 25oC.

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

No special requirements for disposal.

Lucis Pharma Ltd

14 Aston Magna, Moreton-in-Marsh

Gloucestershire

GL56 9QQ, UK

8 MARKETING AUTHORISATION NUMBER(S)

9   DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION