This information is intended for use by health professionals

1. Name of the medicinal product

Carbocisteine unither pharmaceuticals 750mg/10ml sugar-free oral solution in sachet

Carbocisteine 750mg/10ml sugar-free oral solution in sachet

2. Qualitative and quantitative composition

Each 10 ml of oral solution contains 750 mg of carbocisteine

Excipients with known effect:

sodium methyl para-hydroxybenzoate (E 219) 15mg per dose

sorbitol liquid (non-crystallising) 1.3g per dose

maltitol, liquid 1.3g per dose

sodium 97.5mg per dose

ethanol (trace)

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Oral solution in sachet.

Limpid, viscous, light brown solution.

4. Clinical particulars
4.1 Therapeutic indications

This medicine 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

FOR ADULTS AND CHILDREN OVER 15 YEARS ONLY

Oral route.

One 10 ml sachet contains 750 mg of carbocisteine.

The standard dose is 750 mg, 3 times a day (i.e. 2250mg), or 1 sachet, 3 times a day. The dose should be reduced to 1500mg daily in divided doses when a satisfactory response is obtained i.e. dose reduction from 3 sachets per day to 2 sachets per day (taken separately).

This medicine is appropriate for patients following a low sugar or low calorie diet.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

Active peptic ulceration

4.4 Special warnings and precautions for use

Special warning

Productive coughs that represent a fundamental element in bronchial-pulmonary defences should be respected.

The association of bronchial mucous modifiers with anti-cough medicines and/or substances that dry out secretions (atropinic) is not rational.

This medicine contains sodium methyl para-hydroxybenzoate (E219) and can cause allergic reactions (sometimes late onset).

This medicine contains maltitol and sorbitol. It is not recommended for fructose-intolerant patients (rare hereditary disease).

This medicine contains small amounts of ethanol (alcohol), less than 100 mg per sachet.

This medicine contains sodium. This medicine contains 97.5 mg (4.24 mmol) of sodium per dose.

This should be taken into account in patients following strict low sodium diets.

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 rational.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies have not shown any teratogenic effects. In the absence of teratogenic effects in animals, malformations are not expected in humans. Currently, substances responsible for malformations in humans were found to be teratogenic in animals during properly carried out studies in two different species.

From a clinical point of view, no malformations or foetotoxicity have occurred.

However, the follow-up of pregnancies in which there is exposition to carbocisteine is not sufficient to exclude all risks.

Consequently, carbocisteine should not be used during pregnancy unless necessary.

Breast-feeding

There is no data on carbocisteine passing into breast milk.

However, given its low toxicity, the potential risk for children seems negligible if being treated with this medicine. Consequently, breast feeding is possible.

4.7 Effects on ability to drive and use machines

The medicinal product has negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The evaluation of undesirable effects is based on the following information on frequencies:

Very common (≥ 1/10)

Rare (≥ 1/10,000 to < 1/1,000)

Immune system disorders

There have been reports of anaphylactic reactions and fixed drug eruption.

Gastrointestinal disorders

Very common: stomach pains, nausea, diarrhoea.

There have been reports of gastrointestinal bleeding occurring during treatment with carbocisteine.

Frequency not known: vomiting, gastrointestinal bleeding.

In such cases, it is advised to reduce the dosage.

Skin and subcutaneous tissue disorders

Rare: itching, rash, erythematous rash, or swelling in the face.

There have been reports of allergic skin eruptions. Isolated cases of bullous dermatitis such as Stevens-Johnson syndrome 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.

4.9 Overdose

Gastric lavage may be beneficial, followed by observation. Gastrointestinal disorders is the most likely symptom of overdosage. In such cases, it is advised to reduce the dosage.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: mucolytic, ATC code: R05CB03

(R: respiratory system)

Carbocisteine is a mucolytic agent that modifies mucous secretions. It acts during the mucous gel phase, most likely by breaking up the disulfide bonds in glycoproteins, thereby favouring expectoration.

5.2 Pharmacokinetic properties

After oral administration, carbocisteine is quickly absorbed; maximum plasma concentration is reached in two hours.

Its bioavailability is low, less than 10% of the administered dose, most likely via intraluminal metabolism with a significant hepatic first pass effect.

Elimination half-life is about 2 hours. Carbocisteine and its metabolites are excreted primarily through the kidneys.

5.3 Preclinical safety data

Tests in a wide range of animal species have revealed no significant toxicity. Serious adverse events associated with the use of carbocisteine have not been reported. Even symptomatic adverse events are very rare.

6. Pharmaceutical particulars
6.1 List of excipients

Saccharin sodium

Sodium methyl para-hydroxybenzoate (E 219)

Hydroxyethylcellulose

Caramel/vanilla flavouring (contains ethanol)

Sorbitol liquid (non-crystallising)

Maltitol liquid

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.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

10 ml sachet (PET/Aluminium/PE); box of 10, 12 or 15.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Intrapharm Laboratories Limited,

The Courtyard Barns,

Choke Lane,

Cookham Dean,

Maidenhead,

Berkshire,

SL6 6PT,

UNITED KINGDOM.

8. Marketing authorisation number(s)

PL 17509/0074

9. Date of first authorisation/renewal of the authorisation

26th March 2015

10. Date of revision of the text

7th November 2017