This information is intended for use by health professionals

1. Name of the medicinal product

Carbocisteine 375 mg Capsules, hard

2. Qualitative and quantitative composition

Each capsule contains 375 mg Carbocisteine.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Capsule, hard

Hard gelatin capsules with size No 1(app. 19.4 ± 0.3 mm), filled with homogenous white powder. The colour of the capsule body and of the capsule cap is dull-yellow opaque.

4. Clinical particulars
4.1 Therapeutic indications

Carbocisteine is a mucolytic agent for the adjunctive therapy of respiratory tract disorders characterized by excessive, viscous mucus, including chronic obstructive airways disease.

4.2 Posology and method of administration

Posology

Adults and elderly

Dosage is based upon an initial daily dosage of 2250 mg Carbocisteine in divided doses, reducing to 1500 mg daily in divided doses when a satisfactory response is obtained e.g. two capsules three times a day reducing to one capsule four times a day.

Paediatric population

Carbocisteine capsules are not recommended for children.

Method of administration

For oral use.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Use in patients with active peptic ulceration.

4.4 Special warnings and 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. If gastrointestinal bleeding occurs, patients should discontinue medication.

4.5 Interaction with other medicinal products and other forms of interaction

None known.

4.6 Fertility, pregnancy and lactation

Pregnancy

Although tests in mammalian species have revealed no teratogenic effects, Carbocisteine is not recommended during the first trimester of pregnancy.

Breast-feeding

Use in lactation: Effects not known.

Fertility

There is no consistent evidence on the effects of this product on fertility in males or females.

4.7 Effects on ability to drive and use machines

None known.

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 gastrointestinal bleeding occurring during treatment with Carbocisteine.

Frequency not known (cannot be estimated from the available data): vomiting, gastrointestinal bleeding.

Skin and subcutaneous tissue disorders

There have been reports of skin rashes and allergic skin eruptions. Isolated cases of bullous dermatitis 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.

4.9 Overdose

Gastric lavage may be beneficial, followed by observation. Gastrointestinal disturbance is the most likely symptom of Carbocisteine overdosage.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Cough and cold preparations, mucolytics.

ATC code: R05CB03

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. 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. 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 absorbed from the GI tract. In an 'in-house' study, at steady state (7 days) Carbocisteine capsules 375 mg given as 2 capsules 3 times a day to healthy volunteers gave the following pharmacokinetic parameters:

Plasma Determinations

Mean

Range

Tmax (Hr)

2.0

1.0 - 3.0

T½ (Hr)

1.87

1.4 - 2.5

KEL (Hr-1)

0.387

0.28 - 0.50

AUC0-7.5 (mcg.Hr.ml-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

There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

6. Pharmaceutical particulars
6.1 List of excipients

Capsule Contents:

Mannitol;

Maize starch;

Croscarmellose sodium;

Sodium laurilsulfate, grade K12;

Colloidal anhydrous silica;

Magnesium stearate.

Capsule Shell:

Gelatine;

Red Iron Oxide E 172;

Titanium dioxide E171;

Yellow iron oxide E 172.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 (three) years.

6.4 Special precautions for storage

Store below 30 °C.

6.5 Nature and contents of container

The capsules are blister-packed in transparent PVC/PVDC/aluminium hard foil. Each blister strip contains 10 capsules.

Pack sizes: 20, 30, 50 or 120 capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Dr. Reddy's Laboratories (UK) Ltd.

6 Riverview Road, Beverley, East Yorkshire,

HU17 0LD

United Kingdom

8. Marketing authorisation number(s)

PL 08553/0588

9. Date of first authorisation/renewal of the authorisation

14/02/2017

10. Date of revision of the text

07/06/2019