Carbocisteine 375 mg Capsules, hard Milpharm Limited

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.

4.1 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 including the 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** This formulation is not recommended for children. The normal daily dosage is 20 mg/kg body weight in divided doses. It is recommended that this is achieved with Carbocisteine Paediatric Syrup. **Method of administration** Carbocisteine capsules are 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. **Carbocisteine contains sodium** This medicine contains less than 1 mmol sodium (23 mg) per each hard capsule, that is to say essentially 'sodium-free'.4.5 Interaction with other medicinal products and other forms of interaction None known.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 breast-feeding. The use of carbocisteine in breastfeeding women is not recommended.4.7 Effects on ability to drive and use machines Carbocisteine has no or negligible influence on the ability to drive and use machines.4.8 Undesirable effects The following CIOMS frequency rating is used, when applicable: 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** There have been reports of anaphylactic reactions, allergic skin eruption 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 Carbocisteine overdosage.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: respiratory system, mucolytics, 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. 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 t.d.s. 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 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 **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 ºC.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.