Mucitus

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MUCITUS (MUCITUS)

Composition:

Active substance: erdosteine;

1 capsule contains 150 mg or 300 mg of erdosteine;

Excipients: microcrystalline cellulose, povidone, sodium starch glycolate (type A), magnesium stearate;

Capsule shell for 150 mg capsules: brilliant blue (E 133), carmoisine (E 122), quinoline yellow (E 104), titanium dioxide (E 171), gelatin;

Capsule shell for 300 mg capsules: brilliant blue (E 133), titanium dioxide (E 171), gelatin.

Pharmaceutical form. Capsules.

Main physicochemical characteristics:

150 mg capsules: hard gelatin capsules with a brown cap and a blue body, containing white or almost white powder;

300 mg capsules: hard gelatin capsules with a blue cap and a white body, containing white or almost white powder.

Pharmacological Properties.

Pharmacodynamics.

Erdosteine is a mucolytic compound whose action is mediated by its active metabolites. These metabolites possess free thiol groups that disrupt disulfide bridges linking glycoprotein fibers, thereby reducing the elasticity and viscosity of mucus. As a result, the drug facilitates the clearance of secretions from the respiratory tract and enhances the effectiveness of the mucociliary clearance mechanism in removing mucus and mucopurulent exudates from both upper and lower respiratory pathways.

Erdosteine also reduces the adhesive capacity of Gram-positive and Gram-negative bacteria to the respiratory epithelium. Due to this antibacterial anti-adhesive effect, demonstrated in in vitro studies, bacterial colonization of the respiratory tract may be reduced, thereby lowering the risk of bacterial superinfection.

Erdosteine also acts as a scavenger of free oxygen radicals, prevents their local formation, and significantly reduces the level of 8-isoprostane, a marker of lipid peroxidation. The anti-inflammatory effect of erdosteine, observed both in vitro and in vivo, is further supported by reduced synthesis of certain proinflammatory cytokines (IL-6, IL-8).

Erdosteine prevents inhibition of alpha-1-antitrypsin by tobacco smoke, thus protecting against damage caused by smog or smoking.

Moreover, erdosteine increases IgA concentration in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) and prevents granulocyte inhibition induced by smoking. Erdosteine also increases amoxicillin concentration in bronchial secretions; therefore, the therapeutic effect when these agents are used concomitantly is faster compared to monotherapy with amoxicillin alone. In patients with COPD, 8-month erdosteine therapy reduced the frequency of disease exacerbations and improved quality of life.

The drug's effect becomes apparent approximately 3–4 days after initiation of treatment. Erdosteine itself does not contain free SH radicals; therefore, it has minimal impact on the gastrointestinal tract when administered at recommended doses, and the adverse event profile related to the gastrointestinal tract is comparable to that observed with placebo.

Pharmacokinetics.

Erdosteine is rapidly absorbed and metabolized in the liver, forming at least three active metabolites, the most abundant (in percentage terms) and active of which is N-thiodiglycolylhomocysteine (metabolite 1, or M1). The main pharmacokinetic parameters (for M1) are: maximum concentration (Cmax) – 3.46 µg/mL; time to reach maximum concentration (Tmax) – 1.48 hours; area under the concentration-time curve (AUC) – 12.09 mg/L/h. The plasma protein binding rate of erdosteine is 64.5%. Elimination occurs via urine and feces, where only inorganic sulfates have been detected.

The elimination half-life (overall for the product, i.e., for erdosteine and its metabolites) exceeds 5 hours. Repeated administration and food intake do not alter the pharmacokinetic profile of the product. No signs of accumulation or enzyme induction have been observed.

In hepatic impairment, increased Cmax and AUC values have been observed.

Furthermore, in severe hepatic dysfunction, an increased elimination half-life of the drug has been noted. In severe renal insufficiency, there is a risk of metabolite accumulation.

Clinical characteristics.

Indications.

Reduction of viscosity and facilitation of expectoration of bronchial secretions in the treatment of acute and chronic diseases of the upper and lower respiratory tract, such as bronchitis, rhinitis, sinusitis, laryngopharyngitis, exacerbations of chronic bronchitis, chronic obstructive pulmonary disease (COPD), hypersecretory bronchial asthma, and bronchiectasis.

Prevention of recurrent episodes of infections and complications following surgical procedures, such as pneumonia or partial lung atelectasis.

This drug is also indicated as concomitant therapy with antibiotics in cases of bacterial respiratory tract infections.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients containing free SH-groups.

The use of this drug should be discontinued in the following cases:

• in liver disorders (e.g., increased serum levels of alkaline phosphatase or transaminases);
• in renal insufficiency (creatinine clearance < 25 ml/min);
• in homocystinuria (this medicinal product is a source of homocysteine, and currently there are no available data on the use of erdosteine in cases of congenital amino acid metabolism disorders, especially in patients required to follow a methionine-free diet);
• in active peptic ulcer disease.

Interaction with other medicinal products and other forms of interaction.

No undesirable interactions have been observed with other medicinal products commonly used in respiratory tract infections and COPD, such as theophylline, bronchodilators, erythromycin, amoxicillin, or sulfamethoxazole. Erdosteine potentiates the effect of certain antibiotics (e.g., amoxicillin, clarithromycin), which may be used therapeutically. A synergistic effect of erdosteine has been demonstrated when administered concomitantly with budesonide and salbutamol.

Special precautions for use

If classical symptoms of hypersensitivity occur, erdosteine therapy should be discontinued immediately.

Concomitant use of antitussive agents is not advisable and may lead to accumulation of secretions in the bronchial tree, increasing the risk of superinfection or bronchospasm.

Use during pregnancy or breastfeeding

During studies, no cases of embryotoxic or fetotoxic effects were observed; however, information regarding the use of erdosteine during pregnancy or breastfeeding is limited. Therefore, the drug should be used during pregnancy, especially in the first trimester, only if absolutely necessary, after careful assessment of the benefit/ risk ratio for the fetus and mother.

Ability to influence reaction rate while driving or operating machinery

No negative effect on the ability to drive vehicles or operate machinery or to concentrate attention has been observed.

Method of administration and dosage.

Mucitus should be administered orally, regardless of food intake.

The recommended dose for children aged 8 to 12 years is 150 mg twice daily; for adults and children aged 12 years and older – 300 mg twice daily.

The duration of treatment is determined individually by a physician. In acute uncomplicated conditions, the drug should be used for 5–10 days. The treatment duration for chronic conditions is determined by a physician. Dosage adjustment in elderly patients is not required.

Children.

The drug is contraindicated in children under 8 years of age.

Overdose.

There have been no reported cases of overdose to date.

In case of overdose or accidental ingestion by a child, symptomatic treatment is recommended (gastric lavage and other supportive measures).

Side effects.

Erdosteine may occasionally cause undesirable gastrointestinal reactions such as gastric burning sensation and pain, nausea, vomiting, and, rarely, diarrhea. At the beginning of therapy, agueusia or dysgeusia have been observed in a few cases. Hypersensitivity reactions such as skin rashes, unexpected hyperpyrexia, erythema, or Quincke's edema occur rarely. Headache is possible from the nervous system.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging. 6 capsules per strip, 2 or 5 strips per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Macleods Pharmaceuticals Limited.

Manufacturer's address and site of operations.

Phase II, Plot No. 12, 15, 21, 23, 24, 25, 26, 27, 28 and 30, Survey No. 366, Premier Industrial Estate, Kachigam, Daman, 396210, India.