Fluimucil

FLUIMUCIL

Composition:

Active ingredient: acetylcysteine;

1 effervescent tablet contains 600 mg of acetylcysteine;

Excipients: anhydrous citric acid, sodium bicarbonate, aspartame (E 951), lemon flavoring.

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white, round tablets with a characteristic lemon odor and a slightly sulfurous smell.

Pharmacotherapeutic group. Mucolytic agents.

ATC Code: R05C B01.

Pharmacological properties.

Pharmacodynamics.

N-acetyl-L-cysteine (NAC) exerts a pronounced mucolytic effect on mucous and mucopurulent secretions by depolymerizing mucoprotein complexes and nucleic acids that increase the viscosity of the gel-like and purulent components of sputum and other secretions. Additional properties: reduction of induced hyperplasia of mucocytes, increased surfactant production due to stimulation of type II pneumocytes, stimulation of mucociliary apparatus activity, thereby improving mucociliary clearance.

N-acetyl-L-cysteine also exerts a direct antioxidant effect due to the presence of a nucleophilic free thiol (SH) group capable of directly interacting with electrophilic groups of reactive oxygen species. Of particular interest is the fact that NAC prevents inactivation of α-1-antitrypsin – an enzyme that inhibits elastase – by hypochlorous acid (HOCl), a strong oxidant produced by myeloperoxidase in activated phagocytes.

Furthermore, the molecular structure of NAC allows it to easily penetrate cell membranes. Inside the cell, NAC is deacetylated to form L-cysteine, an essential amino acid for glutathione synthesis. In addition, as a precursor of glutathione, NAC exhibits an indirect antioxidant effect. Glutathione is a highly active tripeptide found in various animal tissues and is essential for maintaining cellular functional capacity and morphological integrity. It is actually part of the most important intracellular defense mechanism against reactive oxygen species, both exogenous and endogenous, and against certain cytotoxic substances, including paracetamol.

Paracetamol exerts cytotoxic effects through progressive depletion of glutathione. NAC plays a primary role in maintaining adequate glutathione levels, thus enhancing cellular protection. As a result, NAC is a specific antidote in paracetamol poisoning.

In patients with COPD, administration of 1200 mg NAC daily for 6 weeks led to significant improvement in inspiratory volume and FEV1 (forced vital capacity of the lungs), possibly due to reduced air trapping.

In patients with idiopathic pulmonary fibrosis (IPF), oral administration of acetylcysteine 600 mg three times daily for one year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve lung vital capacity (VC) and diffusing capacity of the lungs measured by single breath carbon monoxide method.

As inhaled therapy over one year, NAC contributed to reduced disease progression in patients with IPF.

When used in very high doses (up to 3000 mg daily for 4 weeks), NAC did not cause significant toxicity in patients with cystic fibrosis.

The antioxidant efficacy of NAC is associated with a marked reduction in elastase activity in sputum, which is the most significant indicator of lung function in patients with cystic fibrosis. In addition, during treatment, a reduction in the number of neutrophils in the airways was observed, as well as a decrease in the number of neutrophils actively releasing elastase-rich granules.

Pharmacokinetics.

Absorption

In humans, after oral administration, acetylcysteine is completely absorbed. Due to metabolism in the intestinal wall and first-pass effect, the bioavailability of acetylcysteine after oral administration is very low (approximately 10%). No differences have been observed among various dosage forms. In patients with various respiratory and cardiovascular diseases, maximum plasma concentration of NAC is reached within 1–3 hours after administration and remains high for 24 hours.

Distribution

Acetylcysteine is distributed in the body both in unchanged form (20%) and as metabolites (active) (80%), predominantly found in the liver, kidneys, lungs, and bronchial secretions. The volume of distribution of NAC ranges from 0.33 to 0.47 L/kg. Plasma protein binding is about 50% at 4 hours after administration and decreases to 20% at 12 hours.

Metabolism

After oral administration, NAC is rapidly and extensively metabolized in the intestinal wall and liver. The resulting metabolite, cysteine, is considered active. Further, acetylcysteine and cysteine are metabolized via the same pathway.

Elimination

Approximately 30% of the dose is excreted by the kidneys. After oral administration, the elimination half-life (T1/2) of NAC is 6.25 (4.59–10.6) hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic bronchopulmonary diseases associated with increased sputum production.

Paracetamol overdose.

Contraindications.

Known hypersensitivity to acetylcysteine or any of the excipients.

Active peptic ulcer disease of the stomach or duodenum, hemoptysis, pulmonary hemorrhage.

Children under 12 years of age. This is not a contraindication for use in the treatment of paracetamol overdose.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been conducted only in adults.

Concomitant use of acetylcysteine with antitussive agents may increase sputum retention due to suppression of the cough reflex.

Activated charcoal reduces the effectiveness of acetylcysteine.

Information about inactivation of antibiotics by acetylcysteine has been obtained only from in vitro experiments involving direct mixing of substances. If concomitant use of acetylcysteine and any oral medications (including antibiotics) is necessary, they should be administered at least 2 hours apart. This does not apply to loracarbef.

Concomitant administration of nitroglycerin and acetylcysteine has been shown to cause significant hypotension and dilation of the temporal artery. If concomitant use of nitroglycerin and acetylcysteine is required, patients should be monitored for hypotension, which may be severe. Patients should be warned about the possibility of headache.

Concomitant use of acetylcysteine and carbamazepine may lead to subtherapeutic levels of carbamazepine.

Effect on laboratory tests

Acetylcysteine may interfere with colorimetric assays for salicylates and with the determination of ketone bodies in urine.

Special precautions for use.

Patients with bronchial asthma should be under strict medical supervision during treatment due to the possible development of bronchospasm. If bronchospasm occurs, treatment with acetylcysteine should be discontinued immediately.

The drug should be used with caution in patients with a history of gastric or duodenal ulcer, especially when taking other medications that irritate the gastric mucosa.

Acetylcysteine should be administered with caution to patients with liver or kidney disease to avoid accumulation of nitrogen-containing substances in the body.

Acetylcysteine affects histamine metabolism; therefore, long-term therapy should not be prescribed to patients with histamine intolerance, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, pruritus).

The use of acetylcysteine, especially at the beginning of treatment, may cause liquefaction of bronchial secretions and increase their volume. If the patient is unable to effectively expectorate sputum, postural drainage and bronchoaspiration are required.

A mild sulfurous odor is not an indication of drug deterioration; it is characteristic of the active ingredient.

Fluimucil contains aspartame, a phenylalanine derivative, which may be hazardous for patients with phenylketonuria.

A single dose of Fluimucil 600 mg effervescent tablets contains 6.82 mmol (156.74 mg) of sodium. This should be considered by patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy

Clinical data on the use of acetylcysteine in pregnant women are limited. Animal studies have not revealed direct or indirect adverse effects on reproductive toxicity.

As a precautionary measure, use of Fluimucil effervescent tablets should be avoided during pregnancy.

Before using the drug during pregnancy, potential risks should be weighed against expected benefits.

Breastfeeding

There is no information on the passage of acetylcysteine and/or its metabolites into breast milk. Risk to the infant cannot be excluded.

A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Fluimucil therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Data on the effect of acetylcysteine on human fertility are lacking. Animal studies have not shown harmful effects on fertility at recommended doses.

Ability to affect reaction rate when driving or operating machinery.

There is no evidence that acetylcysteine affects the ability to drive or operate machinery.

Method of administration and dosage.

Adults and children aged 12 years and older

One 600 mg effervescent tablet should be dissolved in 1/3 glass of water and taken once daily.

The duration of treatment is determined individually by the physician, depending on the nature of the disease (acute or chronic).

Paracetamol overdose

Within the first 10 hours after ingestion of the toxic substance, administer Fluimucil as soon as possible at a dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 1–3 days.

Fluimucil must be taken immediately after dissolution without delay.

No interaction with food has been reported; there are no recommendations regarding administration in relation to food intake.

Children.

For use in children aged 12 years and older.

Overdose.

There are no data on cases of overdose with oral formulations of acetylcysteine.

Volunteers took 11.2 g of acetylcysteine daily for three months without any serious adverse effects.

Acetylcysteine administered at a dose of 500 mg/kg/day does not cause overdose.

Symptoms.

Overdose may manifest as gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

Treatment.

There is no specific antidote for acetylcysteine poisoning; treatment is symptomatic.

Adverse reactions.

The most common adverse reactions associated with oral administration of acetylcysteine are gastrointestinal reactions. Hypersensitivity reactions, including anaphylactic shock, anaphylactic/anaphylactoid reactions, bronchospasm, angioedema, rash, and pruritus, have been reported less frequently.

In the table below, adverse reactions are listed by system organ classes and frequency of occurrence (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), and not known (cannot be estimated from available data).

Within each group, adverse reactions are listed in order of decreasing severity.

In very rare cases, severe skin reactions such as Stevens-Johnson syndrome and Lyell's syndrome have been reported in association with the use of acetylcysteine. In most cases, at least one other medicinal product may be more likely to have caused the mucocutaneous syndrome. Therefore, if any new skin or mucous membrane changes occur, medical advice must be sought immediately and acetylcysteine should be discontinued without delay.

Cases of reduced platelet aggregation have been observed; however, the clinical significance of this finding is not known.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after marketing authorization of the medicinal product. This enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years. Do not use after the expiry date stated on the packaging.

Storage conditions. No special storage conditions required. Keep out of reach and sight of children.

Incompatibilities.

When dissolving acetylcysteine, glassware should be used and contact with metal and rubber surfaces should be avoided.

It is not recommended to dissolve acetylcysteine together with other medicinal products in the same glass.

Packaging. Effervescent tablets 600 mg, 2 tablets in a blister, 5 blisters in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer. Zambon Switzerland Ltd. / Zambon Switzerland Ltd.

Manufacturer's address.

Via Industria 13, 6814 Cadempino, Switzerland / Via Industria 13, 6814 Cadempino, Switzerland.

Marketing Authorization Holder. Zambon S.P.A. / Zambon S.P.A.

Address of the Marketing Authorization Holder.

Via Lillo del Duca, 10 - 20091 Bresso, Milan, Italy / Via Lillo del Duca, 10 - 20091 Bresso, Milan, Italy.