SALBUTAMOL

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

Composition:

Active substance: salbutamol;

One dose contains salbutamol 100 mcg (as salbutamol sulfate);

Excipient: propellant HFA 134a.

Pharmaceutical form. Pressurized metered dose inhalation aerosol.

Main physicochemical properties: white or almost white suspension.

Pharmacotherapeutic group. Drugs for obstructive airway diseases. Adrenergic drugs for inhalation. Selective beta2-adrenergic agonists. Salbutamol. ATC code R03AC02.

Pharmacological properties.

Pharmacodynamics.

Salbutamol is a selective beta2-adrenergic receptor agonist. At therapeutic doses, it acts on beta2-adrenergic receptors of bronchial smooth muscle, providing rapid (within 5 minutes) and short-term (4–6 hours) bronchodilation in patients with reversible airway obstruction.

Pharmacokinetics.

After inhaled administration, 10 to 20% of the administered dose reaches the lower respiratory tract. The remainder remains in the inhalation device or in the oropharynx, from where it is swallowed. A portion of the dose that reaches the airways is absorbed into lung tissue and enters the systemic circulation but is not metabolized in the lungs.

Once in the systemic circulation, the drug is metabolized in the liver and is excreted primarily by the kidneys, both unchanged and as a phenolsulfate metabolite.

The portion of the drug that is swallowed from the oropharynx is absorbed from the gastrointestinal tract, undergoes first-pass metabolism in the liver to the phenolsulfate compound, and is then excreted by the kidneys. Most of the drug is eliminated from the body within 72 hours. Plasma protein binding is 10%.

Clinical characteristics.

Indications.

Short-term (4 to 6 hours) bronchodilation with rapid onset (within approximately 5 minutes) in airway obstruction.

Relief of asthma attacks in diseases associated with airway obstruction, such as bronchial asthma.

Prevention of bronchospasm attacks induced by allergens or physical exertion.

As part of combination therapy in patients with bronchial asthma.

Contraindications.

History of hypersensitivity to any component of the drug. Do not use salbutamol dosage forms not intended for intravenous administration to suppress uncomplicated premature labor or threatened miscarriage.

Interaction with other medicinal products and other forms of interaction.

Salbutamol must not be used concomitantly with non-selective beta-adrenoreceptor blockers (e.g., propranolol).

Concomitant use of salbutamol with monoamine oxidase inhibitors (MAO inhibitors) is not contraindicated.

Special precautions for use.

To ensure optimal delivery of the medicinal product to the patient's lungs, the patient's inhalation technique should be checked. Patients should be informed that they may experience a different taste compared to that with their previous inhaler.

Patients who are prescribed regular anti-inflammatory therapy (e.g., inhaled corticosteroids) should be advised to continue taking anti-inflammatory medications even when symptoms subside and they do not require salbutamol.

An increased need for bronchodilators, particularly short-acting inhaled beta2-agonists, to control symptoms of bronchial asthma indicates disease exacerbation. Patients should be warned to seek medical help as soon as possible. In such cases, the treatment plan should be reviewed and consideration should be given to increasing the dose of inhaled corticosteroids or initiating a course of oral corticosteroids.

Excessive use of short-acting beta-agonists may mask the progression of the underlying disease and contribute to worsening asthma control, increasing the risk of severe asthma exacerbations and mortality.

Patients using salbutamol more than twice a week on an as-needed basis (excluding prophylactic use before physical exertion) should be assessed for daytime symptoms, nocturnal awakenings, and activity limitations due to asthma to ensure appropriate treatment adjustment, as these patients belong to the risk group for excessive salbutamol use.

Sudden and progressive worsening of bronchial asthma is a life-threatening condition requiring initiation or intensification of corticosteroid therapy. Patients at risk are advised to perform daily peak expiratory flow monitoring.

Bronchodilator agents should not be the sole or primary treatment for patients with severe or unstable bronchial asthma. These patients require regular monitoring, including pulmonary function testing, as severe asthma is a life-threatening condition. Treatment decisions should include consideration of prescribing the maximum recommended doses of inhaled and/or oral glucocorticosteroids.

If the usual dose of salbutamol becomes less effective or its duration of action decreases (less than 3 hours), the patient should consult a physician. Dose escalation or increased frequency of administration should only be performed under medical supervision.

Severe asthma exacerbation should be treated according to standard procedures.

Sympathomimetics, including salbutamol, affect the cardiovascular system. Post-marketing surveillance and published data provide evidence of rare cases of myocardial ischemia associated with salbutamol use. Patients with cardiac conditions (e.g., ischemic heart disease, arrhythmia, or severe heart failure) who are treated with salbutamol should seek medical attention if they experience chest pain or other symptoms suggestive of cardiac disease exacerbation. Symptoms such as dyspnea and chest pain, which may result from either cardiac or respiratory disease, should be carefully evaluated.

Salbutamol should be used with caution in patients with thyrotoxicosis.

Treatment with beta2-agonists may result in severe hypokalemia, particularly with parenteral formulations or nebulizer use. Particular attention should be paid to patients with acute severe asthma, as hypokalemia may be potentiated by concomitant use of xanthine derivatives, steroids, diuretics, and hypoxia. In such cases, serum potassium levels should be monitored.

Salbutamol should be used with caution in patients receiving high doses of other sympathomimetics. Like other beta-adrenergic agonists, salbutamol may cause reversible metabolic changes, such as increased blood glucose levels. Compensation for these changes in diabetic patients is not always possible, and there have been isolated reports of ketoacidosis in such patients. Concomitant corticosteroid therapy may exacerbate this condition.

As with other inhaled medications, paradoxical bronchospasm with immediate worsening of dyspnea after administration may occur. In such cases, alternative formulations or other fast-acting inhaled bronchodilators should be prescribed immediately. Salbutamol should be discontinued promptly, the patient's condition assessed, and, if necessary, another fast-acting bronchodilator prescribed for regular use.

Use during pregnancy or breastfeeding.

Animal studies indicate that salbutamol has reproductive toxicity. The safety of salbutamol use during pregnancy has not been established. Controlled clinical studies on the use of salbutamol in pregnant women have not been conducted. There have been isolated reports of various congenital malformations during intrauterine development, including cleft palate, limb defects, and cardiac abnormalities. Some women during pregnancy received multiple other medicinal products. Salbutamol should be used during pregnancy only if clearly needed.

Salbutamol is likely excreted in breast milk; therefore, it should be administered to breastfeeding women with caution. It is unknown whether salbutamol in breast milk has harmful effects on the newborn/infant. Therefore, its use in breastfeeding women should be limited to cases where the benefit to the mother outweighs the potential risk to the infant.

Ability to influence reaction speed when driving or operating machinery.

There are no data on the effect of salbutamol on driving or operating machinery. If adverse reactions affecting the nervous system (e.g., tremor) occur, driving or operating machinery should be avoided.

Method of Administration and Dosage

Salbutamol is an aerosol intended for inhalation use only via the mouth. For patients who have difficulty coordinating breathing with the use of the inhaler, it is recommended to additionally use a spacer device to facilitate inhalation of inhaled medications.

Adults (including elderly patients)

To relieve acute asthma symptoms, including acute bronchospasm, a minimum initial dose of 1 inhalation (100 mcg) may be used. If necessary, the dose may be increased to 200 mcg (2 inhalations).

For prophylaxis 10–15 minutes before physical exertion or anticipated exposure to allergens, 200 mcg (2 inhalations) should be administered.

For long-term maintenance therapy, 200 mcg (2 inhalations) 4 times daily is recommended. The total daily dose of salbutamol should not exceed 800 mcg (8 inhalations).

Children aged over 12 years should receive the same doses as adults.

Children aged 4 to 12 years

To relieve acute bronchospasm, 1 inhalation (100 mcg) should be administered. If necessary, the dose may be increased to 200 mcg (2 inhalations).

For prophylaxis 10–15 minutes before physical exertion or anticipated exposure to allergens, 100 mcg (1 inhalation) should be administered; if necessary, the dose may be increased to 200 mcg (2 inhalations).

For long-term maintenance therapy, 200 mcg (2 inhalations) 4 times daily is recommended. The total daily dose of salbutamol should not exceed 800 mcg (8 inhalations).

An increased need for beta2-agonists may indicate worsening asthma control. In such cases, the patient's treatment regimen should be reviewed and the need for initiating glucocorticosteroid therapy should be considered.

Instructions for Inhaler Use

Checking the Inhaler

Before first use or after a break in use of 5 days or more, remove the mouthpiece cap by gently pressing on its sides, shake the inhaler well, and release two sprays into the air to ensure proper functioning.

Using the Inhaler

1. Remove the mouthpiece cap by gently pressing on its sides.
2. Ensure that there are no foreign objects inside or outside the inhaler, including in the mouthpiece.
3. Shake the inhaler thoroughly to dislodge any foreign objects and to evenly mix the contents.
4. Hold the inhaler vertically between the thumb and other fingers, with the thumb placed on the body of the inhaler below the mouthpiece.
5. Breathe out fully, then place the mouthpiece between the teeth and close the lips around it without biting.
6. While inhaling slowly and deeply through the mouth, press down on the top of the inhaler to release the salbutamol spray, continuing to inhale slowly and deeply. One press of the inhaler delivers one dose.
7. Hold your breath, remove the inhaler from the mouth, and remove your finger from the top of the inhaler. Continue holding your breath as long as possible.
8. If additional sprays are needed, wait approximately 30 seconds, keeping the inhaler upright. Then repeat steps 3–7.
9. Replace the mouthpiece cap by pressing it into place until it clicks.

IMPORTANT:

Perform steps 5, 6, and 7 without rushing. Inhalation should be as slow as possible just before spraying. For the first few times, practice in front of a mirror. If a "mist" appears around the top of the inhaler or at the corners of the mouth, restart the procedure from step 2.

If your doctor has provided different instructions for using the inhaler, follow those and seek advice if any difficulties arise.

Children. Young children may need assistance; it may be necessary for adults to administer the inhalations. Ask the child to breathe out, and administer the spray immediately after they begin to inhale. It is recommended to practice the technique together. Older children or weakened adults may hold the inhaler with both hands. Place both index fingers on top of the inhaler and both thumbs on the base below the mouthpiece.

Cleaning

The inhaler should be cleaned at least once a week.

1. Remove the metal canister from the plastic inhaler holder and remove the mouthpiece cap.
2. Wash the plastic holder and mouthpiece cap with warm water.
3. Dry them thoroughly inside and out.
4. Reinsert the metal canister and replace the mouthpiece cap.

DO NOT PUT THE METAL CANISTER IN WATER.

Children

The medication is indicated for treatment of children aged 4 years and older.

Overdose

The most common symptoms of salbutamol overdose are transient, pharmacologically induced effects due to beta-agonists, such as tachycardia, tremor, hyperactivity, and metabolic disturbances, including hypokalemia (see sections "Special Warnings" and "Adverse Reactions").

Salbutamol overdose may lead to hypokalemia; therefore, serum potassium levels should be monitored. Cases of lactic acidosis have been reported following high therapeutic doses or overdose of short-acting beta2-agonists. Serum lactate levels should therefore be checked, and metabolic acidosis should be monitored accordingly, especially in the presence of persistent or worsening tachypnea, despite improvement in bronchospasm symptoms such as stridorous breathing.

Side effects

The adverse reactions listed below are classified by organ systems 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), including isolated cases, frequency not known. In general, very common and common adverse effects are determined from clinical trial data, whereas rare, very rare, and those with unknown frequency are derived from spontaneous reports.

Immune system disorders

Very rare: hypersensitivity reactions, including angioedema, urticaria, bronchospasm, arterial hypotension, and collapse.

Metabolism and nutritional disorders

Rare: hypokalemia. Beta2-agonists may potentially cause pronounced hypokalemia.

Nervous system disorders

Common: tremor, headache.

Very rare: hyperactivity.

Cardiac disorders

Common: tachycardia.

Uncommon: palpitations.

Very rare: cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, and extrasystoles.

Frequency not known: myocardial ischemia (see section "Special precautions").

Vascular disorders

Rare: peripheral vasodilation.

Respiratory, thoracic and mediastinal disorders

Very rare: paradoxical bronchospasm.

Gastrointestinal disorders

Uncommon: irritation of the mucous membranes of the mouth and throat.

Musculoskeletal and connective tissue disorders

Uncommon: muscle cramps.

Shelf life.

2 years.

Storage conditions.

Keep out of the reach of children. Store below 30 °C. Do not freeze. Avoid exposure to direct sunlight. Do not disassemble, puncture, or incinerate the canister, even after complete use. The canister is under pressure. Do not expose to temperatures above 50 °C.

Packaging.

Aluminum canister with a metering valve. The canister is equipped with a plastic actuator with a metered nozzle and a dust cap. The canister contains no less than 200 doses of the drug. 1 canister in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

Glaxo Wellcome Production, France.

Manufacturer's address and place of business.

Glaxo Wellcome Production, Zone Industrielle No. 2, 23, rue Lavoisier, 27000 Evreux, France.