Multitrip broncho

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MULTIGRIP BRONCHO

Composition:

Active substance: acetylcysteine;

One sachet contains 600 mg of acetylcysteine;

Excipients: aspartame (E 951), beta-carotene 1 % (CWS), orange essence, sorbitol (E 420).

Pharmaceutical form. Oral powder for solution.

Main physicochemical properties: white or almost white powder containing orange particles.

Pharmacotherapeutic group. Mucolytics. Acetylcysteine.

ATC code R05C B01.

Pharmacological Properties

Pharmacodynamics

Acetylcysteine is an N-acetylated derivative of the natural amino acid L-cysteine.

Acetylcysteine is a mucolytic agent.

Acetylcysteine breaks disulfide bonds in mucus glycoproteins through its sulfhydryl groups, exerting a mucolytic effect on mucoid and purulent-mucous secretions. It reduces the density and viscosity of mucus accumulated in the respiratory tract. It helps regulate lung function by facilitating expectoration and elimination of bronchial secretions.

Acetylcysteine prevents or minimizes hepatotoxicity caused by acetaminophen. Normally, small amounts of acetaminophen are metabolized by the cytochrome P450 microsomal enzyme system into a reactive intermediate metabolite, which is then metabolized via conjugation with glutathione and ultimately excreted in urine. However, high doses of acetaminophen can deplete glutathione, reducing the inactivation of this toxic metabolite. Acetylcysteine can act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.

Paracetamol exerts cytotoxic effects through progressive depletion of glutathione. Acetylcysteine plays a key role in maintaining adequate glutathione levels, thereby enhancing cellular protection. Therefore, acetylcysteine is the specific antidote in paracetamol poisoning.

In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg of acetylcysteine daily for 6 weeks resulted in a significant increase in inspiratory volume and forced vital capacity (FVC), possibly due to reduced air trapping.

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

The use of acetylcysteine as inhalation therapy for one year reduced the rate of disease progression in patients with IPF.

When administered at very high doses (up to 3000 mg daily for 4 weeks) in patients with cystic fibrosis, acetylcysteine did not produce significant toxic effects.

The antioxidant efficacy of acetylcysteine is associated with a pronounced reduction in sputum elastase activity, 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 respiratory tract was observed, as well as a decrease in the number of neutrophils actively releasing elastase-rich granules.

Pharmacokinetics

Absorption

In humans, acetylcysteine is completely absorbed after oral administration. 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 acetylcysteine is reached within 1–3 hours after administration and remains elevated for up to 24 hours.

Distribution

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

Metabolism

After oral administration, acetylcysteine is rapidly and extensively metabolized in the intestinal wall and liver. The metabolite cysteine is considered to be active. Subsequently, both acetylcysteine and cysteine are metabolized via the same pathway.

Elimination

Approximately 30% of the administered dose is excreted by the kidneys. After oral administration, the elimination half-life (T_1/2) of acetylcysteine is 6.25 (4.59 – 10.6) hours.

Clinical Characteristics

Indications

Acute and chronic diseases of the bronchopulmonary system associated with increased sputum production.

Paracetamol overdose.

Contraindications

Known hypersensitivity to acetylcysteine or to any of the excipients of the medicinal product.

Acute stage of gastric and duodenal ulcer, hemoptysis, pulmonary hemorrhage.

Children under 14 years of age. However, this is not a contraindication for use in cases of paracetamol overdose.

Since the medicinal product contains aspartame as a sweetener, it should not be used in patients with phenylketonuria.

Interaction with other medicinal products and other forms of interaction

Interaction studies have been conducted only in adults.

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

Activated charcoal reduces the effectiveness of acetylcysteine.

Inactivation of antibiotics by acetylcysteine is known; however, these data were obtained only in in vitro experiments with direct mixing of substances. When used concomitantly with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, and aminoglycosides, interaction with the thiol group of acetylcysteine may occur, leading to reduced activity of both agents. Therefore, the interval between administration of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.

Significant arterial hypotension and dilatation of temporal arteries have been observed when nitroglycerin and acetylcysteine are administered concomitantly. In cases where concomitant use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for arterial hypotension, which may be severe, and should be warned about the possibility of headache.

Acetylcysteine can act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.

Paracetamol (acetaminophen)

Acetylcysteine is a component of glutathione and participates in conjugation with the active metabolite of paracetamol, thereby helping to protect against hepatotoxic effects. There is no direct interaction between paracetamol and acetylcysteine.

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

Acetylcysteine may cause bronchial hypersecretion. In such cases, if the cough reflex or expectoration is inadequate, it is essential to ensure the maintenance of airway patency.

There is no evidence that acetylcysteine at oral doses up to 600 mg causes bronchospasm or anaphylactoid reactions. It is important to remember that the drug must not be inhaled during preparation, especially in patients with allergies or asthma.

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

Caution is recommended when administering the drug to patients with a history of gastric or duodenal ulcer, particularly when other medications that irritate the gastric mucosa are taken concomitantly.

Acetylcysteine should be administered with caution in patients with hepatic or renal impairment to avoid accumulation of nitrogen-containing substances in the body.

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

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

A mild sulfurous odor is not an indication of deterioration in drug quality but is characteristic of the active substance.

Mucolytic agents may cause bronchial obstruction in children under 2 years of age. Due to physiological characteristics of the respiratory system in children of this age group, the ability to clear respiratory secretions is limited. Therefore, mucolytics should not be used in children under 2 years of age.

Aspartame. The excipient aspartame is a phenylalanine derivative and may be hazardous for patients with phenylketonuria.

Sorbitol. If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product due to its sorbitol content.

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 function.

As a precautionary measure, use of the drug during pregnancy should be avoided.

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

Breastfeeding

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

A decision should be made whether to discontinue breastfeeding or to discontinue/abstain from the use of the medicinal product Multi Grip Broncho, taking into account the benefits of breastfeeding for the infant and the benefits of therapy for the woman.

Fertility

There are no data on the effect of acetylcysteine on human fertility. Animal studies have not revealed a risk of harmful effects on fertility in humans when the drug is used at recommended doses.

Ability to influence the speed of reactions while driving or operating machinery

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

Dosage and Administration

Adults and children aged 14 years and older

Dissolve the contents of 1 sachet in ½ glass of water. Take 1 sachet per day.

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

Paracetamol overdose

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

Multigrip Broncho should be taken without delay immediately after dissolution.

When dissolving acetylcysteine, use glassware and avoid contact with metal and rubber surfaces.

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

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

Children

Not recommended for children under 14 years of age.

Overdose

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

Volunteers took 11.2 g of acetylcysteine per day for three months without experiencing any serious adverse effects.

Acetylcysteine, when taken at doses 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 reaction, bronchospasm, angioedema, rash, and pruritus, have been reported less frequently.

The table below lists adverse reactions by system organ class 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), frequency 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 connection with the use of acetylcysteine. However, in most of the reported cases, at least one other medicinal product was more likely to have caused these reactions. Therefore, if any new changes appear on the skin or mucous membranes, acetylcysteine should be discontinued immediately and medical advice should be sought.

Cases of reduced platelet aggregation have been observed; however, the clinical significance of this phenomenon is unknown.

Expectorant agents should not be used simultaneously with cough suppressants.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep in the original packaging to protect from light. Keep out of reach of children.

Packaging

3 grams per sachet, with 2, 10, 20, or 30 sachets per cardboard box.

Availability category

Over-the-counter (without prescription).

Manufacturer

Bilim Ilac San. ve Tic. A.S.

Manufacturer's address and location of business operations

Gebze Organize Sanayi Bolgesi 1900 Sokak, No. 1904 Gebze, Kocaeli, Turkey.

Marketing Authorization Holder

Delta Medical Promotions AG.

Address of Marketing Authorization Holder

Othmarstrasse 26, Zurich CH-8001, Switzerland.