Nebuvent-n
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEBUVENT-N (NEBUVENT-N)
Composition:
Active substance: salbutamol;
1 ampoule (2.5 mL) contains 2.5 mg of salbutamol (in the form of salbutamol sulfate);
Excipients: sodium chloride, sulfuric acid, water for injections.
Pharmaceutical form. Solution for inhalation.
Main physicochemical properties: clear, colorless liquid.
Pharmacotherapeutic group. Drugs for the treatment of obstructive respiratory diseases. Adrenergic agents for inhalation use. Selective beta2-adrenoreceptor 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.
Pharmacokinetics.
After inhalation, 10 to 20% of the administered dose reaches the lower airways. The remainder remains in the delivery system or in the oropharynx, from where it is swallowed. Part of the dose that reaches the airways is absorbed into lung tissue and enters the systemic circulation but is not metabolized in the lungs.
The bronchodilating effect of the drug begins within 5 minutes after inhalation, and the duration of action lasts 4–6 hours.
After entering the systemic circulation, the drug is metabolized in the liver and is excreted mainly by the kidneys, primarily in unchanged form and as a phenolsulfate metabolite.
The portion of the dose that reaches the gastrointestinal tract from the oropharynx is absorbed from the gastrointestinal tract, undergoes first-pass metabolism in the liver to form a phenolsulfate compound, and is then excreted by the kidneys.
Clinical characteristics.
Indications.
The drug is indicated for adults and children aged 4 years and older for rapid relief of acute asthma attacks, as well as for treatment of chronic obstructive bronchitis when there is no response to conventional therapy.
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 should not be administered together with non-selective beta-adrenoblockers such as propranolol.
Salbutamol is not contraindicated in patients receiving MAO inhibitors.
Special precautions for use.
The Nebuvent-N preparation should be used only by inhalation through the mouth and must not be administered by injection or oral ingestion.
Treatment of bronchial asthma should be conducted according to a stepwise approach, and the patient's condition should be clinically assessed and monitored using pulmonary function tests.
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 Nebuvent-N.
An increased frequency of use of short-acting inhaled beta2-agonists indicates worsening control of bronchial asthma, and patients should be warned to seek medical help as soon as possible. In such cases, the patient's treatment regimen should be reviewed.
Excessive use of short-acting beta-agonists may mask the progression of the underlying disease and lead 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 evaluated for daytime symptoms, nocturnal awakenings, and activity limitations due to asthma to ensure appropriate adjustment of therapy, 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 should be advised to perform daily peak expiratory flow monitoring.
Patients treated with Nebuvent-N at home should be warned that if the usual effective dose fails to provide relief or the duration of relief is reduced, they should consult a physician and not increase the dose or frequency of administration on their own.
Nebuvent-N should be used with caution in patients receiving high doses of other sympathomimetic agents.
Sympathomimetic agents, including salbutamol, may affect the cardiovascular system. Post-marketing data and published literature report rare cases of myocardial ischemia associated with salbutamol use. Patients with severe cardiovascular disorders (e.g., ischemic heart disease, arrhythmia, or severe heart failure) receiving salbutamol should seek medical help if chest pain or other symptoms suggestive of cardiac disease exacerbation occur. Particular attention should be paid to symptoms such as dyspnea and chest pain, which may result from either cardiac or respiratory disorders.
Salbutamol should be prescribed with caution in patients with thyrotoxicosis.
Cases of acute angle-closure glaucoma have been occasionally observed during treatment with a combination of nebulized/inhaled salbutamol and ipratropium bromide. Therefore, the combination of nebulized/inhaled salbutamol with anticholinergic agents administered via nebulization should be used with caution. Patients should receive appropriate instructions on correct drug use and be warned to avoid contact of the aerosol spray with the eyes.
Treatment with beta2-agonists may result in severe hypokalemia, particularly with parenteral or nebulizer administration. Particular attention should be paid to patients with acute severe bronchial asthma, as hypokalemia may be potentiated by concomitant use of xanthine derivatives, corticosteroids, diuretics, and hypoxia. In such cases, serum potassium levels should be monitored.
As with other inhaled medications, paradoxical bronchospasm with increased wheezing may occur. In such cases, alternative formulations or other fast-acting inhaled bronchodilators should be initiated immediately. Nebuvent-N should be discontinued immediately, and if necessary, other fast-acting bronchodilators should be prescribed on a regular basis.
Like other beta-adrenergic agonists, Nebuvent-N 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 use of corticosteroids may exacerbate this condition.
Very rarely, in patients with acute exacerbation of bronchial asthma treated with high doses of intravenous and nebulized salbutamol, cases of lactic acidosis have been reported (see section "Adverse reactions"). Elevated blood lactate levels may cause dyspnea and compensatory pulmonary hyperventilation, which may be mistakenly interpreted as inadequate anti-asthma therapy, potentially leading to inappropriate intensification of treatment with short-acting beta2-agonists. Therefore, monitoring serum lactate levels and the presence of metabolic acidosis in such patients is recommended.
Use during pregnancy or breastfeeding.
Salbutamol should be used during pregnancy only if the expected benefit to the woman outweighs the potential risk to the fetus. Post-marketing surveillance data include isolated reports of various congenital anomalies, including cleft palate and limb defects, in children whose mothers used salbutamol during pregnancy. Some of these women also used other medications during pregnancy. A definitive causal relationship between such anomalies and salbutamol use has not been established.
Since salbutamol may pass into breast milk, its use during breastfeeding is not recommended, except when the expected benefit to the mother outweighs the potential risk to the infant. It is unknown whether the presence of salbutamol in breast milk has harmful effects on the infant.
Ability to influence reaction rate while driving or operating machinery.
No data are available on the effect of Nebuvent-N 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
Nebuvent-N is intended only for inhalation via the mouth using a nebulizer and must be administered under medical supervision.
The solution must not be injected or swallowed.
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 concomitant glucocorticosteroid therapy should be considered.
Adults (including elderly patients)
The usual initial inhaled dose of salbutamol is 2.5 mg (2.5 mL). This dose may be increased to 5 mg (5 mL). Inhalations may be repeated up to 4 times daily.
For treatment of adult patients with severe airway obstruction, doses may be increased up to 40 mg per day; however, such treatment should be administered in a hospital setting under close medical supervision.
Children aged 12 years and older
Dosage as for adults.
Children aged 4 to 11 years
The usual initial inhaled dose of salbutamol is 2.5 mg (2.5 mL). This dose may be increased to 5 mg (5 mL). Inhalations may be repeated up to 4 times daily.
Other dosage forms of the drug should be used for children under 4 years of age.
The clinical efficacy of nebulized salbutamol in infants under 18 months of age has not been established.
Since transient hypoxemia may occur, the need for additional oxygen therapy should be considered.
Nebuvent-N is generally used undiluted. However, if inhalations need to be prolonged (more than 10 minutes), the contents of the ampoule may be diluted with sterile physiological saline.
Aerosol inhalation can be performed using a special face mask, a T-piece spacer, or through an endotracheal tube. The room where inhalation is performed should be periodically ventilated. If there is a risk of hypoxia due to hypoventilation of inhaled air, the air should be enriched with oxygen.
Dosage and frequency of administration may be increased only by a physician, due to the risk of adverse effects associated with overdose.
Instructions for Use
- Prepare the nebulizer for use.
- Open the pouch and remove the ampoule strip.
- Detach one ampoule from the strip and shake it gently while holding by the neck. Place the remaining ampoules back into the polymer pouch and return them to the cardboard box.
- Hold the ampoule in hand—no leakage of the solution should occur—and twist off the top.
- Insert the ampoule into the nebulizer with the open end downward and press gently. Ensure that all the solution has transferred into the nebulizer.
- Assemble the nebulizer and use as directed.
Use a new ampoule for each administration, and open it immediately before use. Any remaining solution after inhalation must not be stored for future use. Leftover medication should be discarded.
Children
Nebuvent-N is indicated for children aged 4 years and older.
Overdose
The most common signs of salbutamol overdose are transient pharmacologically mediated effects induced by beta-agonists, such as tachycardia, tremor, hyperactivity, and metabolic disturbances, including hypokalemia and lactic acidosis (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions").
Salbutamol overdose may lead to hypokalemia; therefore, serum potassium levels should be monitored. Cases of lactic acidosis have been reported following administration of high therapeutic doses or overdose of short-acting beta2-agonists, so serum lactate levels should be checked. Accordingly, metabolic acidosis should be monitored, especially if persistent tachypnea or worsening of tachypnea occurs despite improvement in bronchospasm symptoms (e.g., reduction in wheezing).
Adverse Reactions
The adverse reactions listed below are classified by organ system and frequency of occurrence. Frequency is defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), including isolated cases. In general, very common and common adverse effects are derived from clinical trial data, whereas rare, very rare, and those with unknown frequency are based on spontaneous reports.
Immune system disorders
Very rare: hypersensitivity reactions, including angioedema, urticaria, bronchospasm, hypotension, and collapse.
Metabolism and nutritional disorders
Rare: hypokalaemia. Potentially severe hypokalaemia may occur during treatment with beta2-agonists.
Frequency unknown: lactic acidosis (see section "Special precautions").
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 unknown: myocardial ischaemia (see section "Special precautions").
As these reports are spontaneous, derived from post-marketing surveillance, the frequencies cannot be reliably estimated.
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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after medicine authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children. Do not store the medicinal product after first opening of the ampoule.
Packaging. 2.5 ml in a polyethylene ampoule. 5 ampoules in an aluminium foil sachet; 2 sachets in a cardboard box.
Prescription status. Prescription only.
Manufacturer. PHARMASELL LLC
Manufacturer's address and location of operations.
3, Prorizna Street, Kvitneve, Brovary District, Kyiv Oblast, 07408, Ukraine