Ascoril expectorant (Solution, Syrup) Instructions for Use

ATC Code

R05C (Expectorants, excluding combinations with antitussives)

Active Substances

Bromhexine (Rec.INN registered by WHO)

Guaifenesin (Rec.INN registered by WHO)

Salbutamol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug with mucolytic, expectorant and bronchodilatory action

Pharmacotherapeutic Group

Combined expectorant

Pharmacological Action

Pharmacodynamics

A combined drug with bronchodilatory, expectorant and mucolytic action.

Bromhexine is a mucolytic agent. It increases the serous component of bronchial secretion and activates the cilia of the ciliated epithelium, thereby providing the expectorant effect of the drug: reducing sputum viscosity, increasing its volume and improving its discharge.

Guaifenesin is a mucolytic and expectorant agent, reduces sputum viscosity, facilitates its removal and promotes the transition of non-productive cough to productive.

Salbutamol is a bronchodilator, a selective agonist of β₂-adrenergic receptors. In therapeutic doses, the drug acts on β₂-adrenergic receptors of bronchial smooth muscles, preventing and/or eliminating bronchospasm, thus reducing airway resistance and increasing lung capacity. The bronchodilatory effect of salbutamol (with reversible airway obstruction) lasts from 4 to 5 hours.

Pharmacokinetics

Bromhexine

Absorption and Distribution

When taken orally, it is almost completely (99%) absorbed from the gastrointestinal tract within 30 minutes. Bromhexine demonstrates dose-proportional linear pharmacokinetics when taken orally in the dose range from 8 mg to 32 mg. Bioavailability is low (subject to the first-pass effect through the liver). Penetrates the placental barrier and the blood-brain barrier.

Metabolism and Excretion

It undergoes demethylation and oxidation in the liver, metabolized to the pharmacologically active ambroxol.

T_1/2 – 15 hours (due to slow reverse diffusion from tissues). Excreted by the kidneys.

In chronic renal failure, the excretion of metabolites is impaired. With repeated use, it may accumulate.

Guaifenesin

Absorption and Distribution

Absorption from the gastrointestinal tract is rapid (within 25-30 minutes after oral administration). Penetrates into tissues containing acidic mucopolysaccharides.

Metabolism and Excretion

Approximately 60% of the administered drug is metabolized in the liver by oxidation to beta-(2-methoxyphenoxy)-lactic acid.

T_1/2 – 1 hour. Excreted by the lungs (with sputum) and by the kidneys, both unchanged and as inactive metabolites.

Salbutamol

Absorption and Distribution

After oral administration, absorption is high. The bioavailability of orally administered salbutamol is about 50%. Food intake reduces the rate of absorption but does not affect bioavailability. C_max of salbutamol and its metabolites in blood plasma is 5.1-11.7 µg% 2.5 hours after oral administration of a 4 mg dose.

Plasma protein binding – 10%. Penetrates the placental barrier.

Metabolism and Excretion

It undergoes significant first-pass metabolism in the liver, converting to phenolic sulfate.

T_1/2 – 3.8-6 hours. Unchanged salbutamol and the metabolite are excreted mainly by the kidneys (69-90%).

Indications

A combined expectorant drug with fixed doses of bromhexine hydrochloride, guaifenesin and salbutamol sulfate is indicated for the symptomatic treatment of productive cough associated with various respiratory diseases, including, among others, the following

• Acute bronchitis, including tracheobronchitis;
• Acute bronchitis caused by respiratory viruses;
• Chronic bronchitis not otherwise specified (NOS);
• Chronic obstructive pulmonary disease (COPD);
• Asthmatic bronchitis;
• Pneumonia.

ICD codes

Dosage Regimen

Syrup

The drug is taken orally.

Adults and children over 12 years old are prescribed 10 ml 3 times/day.

Children aged 6 to 12 years – 5-10 ml 3 times/day; children aged 2 to 6 years – 5 ml 3 times/day.

It is recommended to use a measuring cap.

Shake before use.

The drug should be used for no more than 4-5 days. If symptoms persist for more than 4-5 days, the patient should consult a doctor.

Solution

The drug is taken orally.

Adults and children over 12 years old are prescribed 10 ml 3 times/day; children aged 6 to 12 years – 5-10 ml 3 times/day; children aged 2 to 6 years – 5 ml 3 times/day.

It is recommended to use a measuring cap.

Shake before use.

The drug should be used for no more than 4-5 days. If symptoms persist for more than 4-5 days, the patient should consult a doctor.

Adverse Reactions

The adverse events listed below are distributed by system-organ class and frequency: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10000 and <1/1000) and very rare (<1/10000), including isolated reports. Very common and common events were mainly determined from clinical trial data. Rare, very rare and events with unknown frequency were mainly determined from spontaneous reports.

Gastrointestinal disorders exacerbation of gastric and duodenal ulcers.

Renal and urinary disorders possible pink coloration of urine.

Skin and subcutaneous tissue disorders severe skin adverse reactions, incl. erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis.

Bromhexine

Immune system disorders hypersensitivity, anaphylactic reaction, anaphylactic shock.

Skin and subcutaneous tissue disorders angioedema, rash, urticaria, pruritus.

Respiratory, thoracic and mediastinal disorders bronchospasm.

Gastrointestinal disorders nausea, vomiting, diarrhea and upper abdominal pain.

Guaifenesin

The safety of guaifenesin is based on available data from clinical studies and adverse drug reactions identified during the post-registration period of the drug’s use.

The frequency category is determined according to estimates from clinical and epidemiological studies.

Immune system disorders frequency unknown – hypersensitivity reactions (hypersensitivity, pruritus and urticaria), rash.

Gastrointestinal disorders frequency unknown – epigastric pain, diarrhea, nausea, vomiting.

Salbutamol

Summary of the safety profile

The most common side effect of salbutamol is fine tremor of the hands, which may interfere with work requiring precise hand movements. Tension, restlessness and palpitations may also occur. There have been very rare reports of muscle cramps. Hypersensitivity reactions such as angioedema, urticaria, bronchospasm, hypotension and collapse have been reported rarely. Beta₂-agonist therapy can lead to potentially serious hypokalemia. There have also been reports of intermittent headache. As with other drugs in this class, there have been rare reports of hyperactivity in children.

Immune system disorders very rare – hypersensitivity reactions, including angioedema, urticaria, bronchospasm, hypotension and collapse.

Metabolism and nutrition disorders rare – hypokalemia. Beta-agonist therapy can lead to potentially serious hypokalemia.

Nervous system disorders very common – tremor; common – headache; very rare – hyperactivity.

Cardiac disorders common – tachycardia, palpitations; rare – cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia and extrasystole; frequency unknown – myocardial ischemia*.

Vascular disorders rare – peripheral vasodilation.

Musculoskeletal and connective tissue disorders common – muscle cramps; very rare – sensation of muscle tension.

Reporting of suspected adverse reactions

After registration of a medicinal product, it is important to report suspected adverse reactions. This allows for continuous monitoring of the benefit-risk ratio of the medicinal product.

* Spontaneous reports were received in the post-registration period, therefore it is classified as reactions with unknown frequency.

Contraindications

• Hypersensitivity to the components of the drug;
• Tachyarrhythmia;
• Myocarditis;
• Heart defects (including aortic stenosis);
• Decompensated diabetes mellitus;
• Thyrotoxicosis;
• Glaucoma;
• Hepatic insufficiency;
• Renal insufficiency;
• Gastric and duodenal ulcer in the acute stage;
• Gastric bleeding;
• Fructose intolerance, glucose-galactose malabsorption, sucrase-isomaltase deficiency;
• Pregnancy;
• Breastfeeding period;
• Children under 2 years of age.

With caution diabetes mellitus; arterial hypertension; gastric and duodenal ulcer in remission; hyperthyroidism; angina pectoris; severe cardiovascular diseases; in bronchial diseases accompanied by excessive accumulation of secretions.

Should not be used in combination with beta-blockers.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Use in Renal Impairment

Contraindicated in renal insufficiency.

Pediatric Use

Contraindicated in children under 2 years of age.

Special Precautions

Bromhexine

Should be used with caution in patients with gastric ulcer.

Patients should be warned about a possible increase in mucus secretion.

Only isolated cases of severe skin lesions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), with a temporal relationship to the use of expectorants, in particular bromhexine hydrochloride, have been reported. Most of these can be explained by the severity of the underlying disease and/or the use of concomitant drugs. Furthermore, in the early stage, Stevens-Johnson syndrome or TEN may manifest with nonspecific flu-like prodromal symptoms such as fever, body aches, runny nose, cough and sore throat. Diagnostic errors associated with these nonspecific flu-like prodromal symptoms can lead to the prescription of symptomatic treatment with cough and cold medications. Therefore, if skin or mucous membrane lesions occur, seek medical attention immediately and, as a precaution, discontinue bromhexine hydrochloride.

Guaifenesin

Do not use simultaneously with cough suppressants or combined cold medications.

Guaifenesin colors urine pink.

Excessive use of Guaifenesin may cause kidney stone formation.

If urine is collected within 24 hours after taking guaifenesin, its metabolite may change the color of urine, and 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA) may be detected in the laboratory.

Salbutamol

Bronchodilators should not be used as the sole or main drug in the treatment of patients with severe or unstable asthma. In severe asthma, regular assessment of the condition is necessary, including lung function measurement, because patients are at risk of severe attacks and even fatal outcome. Treating physicians of such patients should consider prescribing them oral corticosteroids and/or the maximum recommended dose of inhaled corticosteroids.

If treatment becomes ineffective, patients should seek medical attention.

The dose or frequency of use should be increased only on the recommendation of a doctor.

Patients taking salbutamol may also take short-acting bronchodilators to relieve symptoms.

An increased need for the use of bronchodilators, especially short-acting inhaled beta₂-agonists, to relieve asthma symptoms indicates a deterioration in disease control. Patients should be instructed to seek medical attention if treatment with short-acting bronchodilators becomes less effective or if they require more inhalations than usual.

In such a situation, patients should be re-evaluated and the need for an intensified course of anti-inflammatory therapy (e.g., higher doses of inhaled corticosteroids or a course of oral corticosteroids) should be considered. Treatment of severe exacerbations of asthma should be carried out in the usual manner.

Patients should be warned that if the effect of usual relief of an attack weakens, or if the usual duration of action of the drug decreases, they should not increase the dose or frequency of use, but seek medical attention.

Salbutamol causes peripheral vasodilation, which may be accompanied by reflex tachycardia and increased cardiac output. Should be used with caution in patients suffering from angina pectoris, severe forms of tachycardia or thyrotoxicosis.

Cardiovascular effects may be observed with the use of sympathomimetics, including salbutamol. Based on some data from the post-registration period, as well as published data, rare cases of myocardial ischemia associated with salbutamol have been noted. Patients with underlying severe heart disease (e.g., coronary artery disease, arrhythmia or severe heart failure) using salbutamol should be warned to seek medical attention if chest pain or other symptoms indicating worsening heart disease occur. Attention should be paid to the evaluation of symptoms such as shortness of breath or chest pain, as they can be of both respiratory and cardiac origin.

Treatment of severe exacerbations of asthma should be carried out in the usual manner.

Use with caution concomitantly with anesthetic agents such as chloroform, cyclopropane, halothane and other halogen-containing drugs.

Salbutamol should not cause difficulty in urination, as it does not stimulate α-adrenergic receptors unlike sympathomimetic agents such as ephedrine. However, there have been reports of difficulty urinating in patients with prostatic hyperplasia.

Potentially serious hypokalemia may occur with the use of beta₂-agonists, mainly by parenteral route or via nebulizer. Particular caution is recommended when treating severe exacerbations of asthma, as hypokalemia may be enhanced by hypoxia and the simultaneous use of xanthine derivatives and corticosteroids. In such situations, it is recommended to monitor serum potassium levels.

Like other β-adrenergic receptor agonists, salbutamol can cause reversible metabolic changes, such as increased blood glucose levels. Patients with diabetes mellitus may be unable to compensate for the increase in blood glucose levels, and ketoacidosis has been reported in such patients. Concurrent use of corticosteroids may enhance this effect.

Effect on ability to drive vehicles and operate machinery

Considering the side effect profile (dizziness, drowsiness and others), it is recommended to refrain from driving vehicles and operating machinery, and from engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions during treatment.

Overdose

Bromhexine

Specific symptoms of overdose in humans have not been described to date. Based on reports of accidental overdose and/or medication error, the observed symptoms are similar to the known side effects when using bromhexine at recommended doses.

Guaifenesin

Symptoms

The effects of acute guaifenesin toxicity include gastrointestinal discomfort, nausea and drowsiness.

Treatment

Symptomatic therapy is carried out.

Salbutamol

Symptoms

The most common signs and symptoms of salbutamol overdose are transient phenomena, pharmacologically mediated by stimulation of β-adrenergic receptors. These include tachycardia, tremor, hyperactivity and metabolic changes including hypokalemia.

Overdose of salbutamol can lead to hypokalemia (pathologically low blood potassium levels). Therefore, it is necessary to monitor serum potassium levels.

The development of lactic acidosis has been observed with the use of high doses, as well as with an overdose of short-acting beta-agonists. Therefore, in case of overdose, monitoring for an increase in serum lactate and the subsequent development of metabolic acidosis may be indicated (especially if tachypnea persists or worsens, despite the elimination of other signs of bronchospasm, such as wheezing).

Nausea, vomiting, and hyperglycemia have been reported predominantly in children and in cases where salbutamol overdose occurred following oral administration.

Treatment

The drug should be discontinued and appropriate symptomatic therapy should be prescribed. Cardioselective beta-blockers (atenolol, bisoprolol, metoprolol) in patients with cardiac symptoms (e.g., tachycardia, palpitations) should be used with caution due to the risk of bronchospasm.

Drug Interactions

Salbutamol

It should be used with caution concomitantly with anesthetic agents such as chloroform, cyclopropane, halothane, and other halogen-containing drugs.

Guanethidine, reserpine, methyldopa, tricyclic antidepressants, and MAO inhibitors may alter the effect of this drug.

Oral salbutamol preparations should not be prescribed concurrently with non-selective beta-blockers, for example, propranolol.

The salbutamol contained in the preparation is not recommended for patients who are receiving MAO inhibitors and/or tricyclic antidepressants.

Diuretics and corticosteroids enhance the hypokalemic effect of salbutamol.

The combined drug Ascoril Expectorant is not prescribed simultaneously with drugs containing codeine and other antitussives, as this impedes the expectoration of liquefied sputum.

The bromhexine contained in the preparation promotes the penetration of antibiotics (erythromycin, cefalexin, oxytetracycline) into the lung tissue.

It is not recommended to use the combined drug Ascoril Expectorant simultaneously with non-selective beta-adrenergic receptor blockers, such as propranolol.

Storage Conditions

The drug should be stored in the original packaging in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.