SYXTEN 5%

Indications

• Chronic bronchitis
• Cystic fibrosis
• Chronic obstructive pulmonary disease (COPD)
• Acute exacerbations of respiratory conditions associated with mucus overproduction

Dosage

Children: For children, the dosage must be determined based on age and weight according to the BNF for Children; refer to the latest guidelines for specific dosing recommendations.

Adults: The usual adult dose is 600 mg once daily, which may vary based on specific conditions and patient response.

Mechanism of action

Carbocisteine acts by stimulating the sialyl transferase enzyme, which helps to restore the equilibrium between sialomucins and fucomucins in bronchial mucus. This mechanism reduces mucus viscosity, enhances mucociliary clearance, and may exhibit antioxidant properties by activating protein kinase B (Akt) phosphorylation, as well as inhibiting inflammatory pathways such as NF-κB and ERK1/2 MAPK. Additionally, it reduces the expression of intracellular adhesion molecule 1 (ICAM-1), which may help limit viral infections in the respiratory tract.

Pharmacodynamics

Carbocisteine is effective in decreasing sputum viscosity, thus alleviating symptoms like cough, dyspnea, and fatigue. Its mucolytic action contributes to the prevention of pulmonary infections by facilitating mucus clearance from the respiratory system. The drug also shows anti-inflammatory properties and reduces oxidative stress, which can be beneficial in respiratory diseases characterized by inflammation.

Pharmacokinetics

Carbocisteine is absorbed from the gastrointestinal tract and has a bioavailability that allows for effective systemic activity. It undergoes metabolic processes in the liver, with metabolites contributing to its therapeutic effects. The elimination half-life and excretion pathways are not specifically detailed, but like many mucolytics, its effects are generally observed within hours after administration.

Contra-indications

• Active peptic ulceration

Adverse effects

• Dizziness
• Fever
• Headache
• Nausea
• Skin reactions

Precautions

• Use with caution in patients with ischaemic heart disease and stroke

Pregnancy

Manufacturer advises avoid in first trimester. Use only if potential benefit outweighs risk, as toxicity in animal studies has been observed.

Breast-feeding

Manufacturer advises to avoid for 12 hours after administration.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Carbocisteine 50 mg per 1 ml oral solution sugar-free | 300 ml
• Carbocisteine 250 mg/5 ml oral solution sugar-free | 300 ml
• Carbocisteine 375 mg capsules
• Carbocisteine 750 mg/10 ml solution for injection

Mechanism of action

The hypersecretion of mucus characterizes serious respiratory conditions including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). It blocks bacterial adherence to cells, preventing pulmonary infections. Glycoproteins (fucomucins, sialomucins and sulfomucins) regulate the viscoelastic properties of bronchial mucus. Increased fucomucins can be found in the mucus of patients with COPD. Carbocisteine serves to restore equilibrium between sialomucins and fucomucins, likely by intracellular stimulation of sialyl transferase enzyme, thus reducing mucus viscosity. A study found that L-carbocisteine can inhibit damage to cells by hydrogen peroxide (H2O2) by activating protein kinase B (Akt) phosphorylation, suggesting that carbocisteine may have antioxidant effects and prevent apoptosis of lung cells. There is some evidence that carbocisteine suppresses NF-κB and ERK1/2 MAPK signalling pathways, reducing TNF-alpha induced inflammation in the lungs, as well as other inflammatory pathways. An in-vitro study found that L-carbocisteine reduces intracellular adhesion molecule 1 (ICAM-1), inhibiting rhinovirus 14 infection, thereby reducing airway inflammation.

Pharmacodynamics

Due to its mucolytic effects, carbocisteine significantly reduces sputum viscosity, cough, dyspnea and fatigue. Additionally, it prevents pulmonary infections by decreasing accumulated mucus in the respiratory tract; this is especially beneficial in preventing exacerbations of COPD caused by bacteria and viruses. It has in-vitro anti-inflammatory activity with some demonstrated action against free radicals.