Budixon Neb suspension for inhalation 0.05% 2 ml No. 20

Instructions for use Budikson Neb suspension for inhalation 0.05% 2 ml No. 20

Composition

active ingredient: budesonide;

1 ml of suspension for nebulization contains 0.25 mg or 0.5 mg of budesonide;

Excipients: disodium edetate, sodium chloride, tween-80, anhydrous citric acid, sodium citrate, water for injections.

Dosage form

Suspension for spraying.

Main physicochemical properties: white homogeneous suspension.

Pharmacotherapeutic group

Inhalants used in obstructive airway diseases. Glucocorticoids. ATX code R03B A02.

Pharmacological properties

Pharmacodynamics.

Budesonide is a glucocorticosteroid with a strong local anti-inflammatory effect, the frequency and severity of side effects of which are lower than those of oral corticosteroids.

Local anti-inflammatory effect

The exact mechanism of action of glucocorticosteroids in the treatment of bronchial asthma is not fully understood. Anti-inflammatory effects involving T cells, eosinophils, and mast cells are thought to play an important role. These reactions involve inhibition of the release of inflammatory mediators and suppression of cytokine-mediated immune responses. The potency of budesonide, measured as affinity for the glucocorticosteroid receptor, is approximately 15 times greater than that of prednisolone.

A clinical trial in asthmatic patients comparing inhaled and oral budesonide formulations at doses designed to achieve similar systemic bioavailability showed a statistically significant superiority of inhaled budesonide over oral budesonide compared to placebo. Thus, the therapeutic effect of standard doses of inhaled budesonide can be largely explained by direct action on the airways.

In a provocation study, pretreatment with budesonide for 4 weeks resulted in a reduction in bronchoconstriction in both immediate and delayed asthmatic reactions.

Airway reactivity

Budesonide has an anti-inflammatory effect, which leads to a decrease in bronchial constriction in allergic reactions of both immediate and delayed types. In patients with bronchial hyperreactivity, budesonide reduces airway reactivity to histamine and methacholine.

Studies have shown that the earlier budesonide treatment is started after the onset of bronchial asthma symptoms, the greater the improvement in lung function can be expected.

In studies with healthy volunteers, when using the drug in the form of a suspension for inhalation, a dose-dependent effect on the level of cortisol in blood plasma and urine was observed. When used in recommended doses, budesonide has significantly less effect on adrenal function than prednisone at a dose of 10 mg, which is confirmed by ACTH tests.

In children aged 3 years and older, no systemic effects were observed after doses up to 400 mg/day. Systemic effects may occur after doses of 400 to 800 mg/day, but are common at doses greater than 800 mg/day.

Exercise-induced bronchial asthma

Inhaled budesonide therapy has been used effectively to prevent exercise-induced asthma attacks.

Effect on plasma cortisol concentration

In studies with healthy volunteers, budesonide nebulizer suspension had a dose-dependent effect on plasma and urinary cortisol levels. Budesonide at recommended doses has significantly less effect on adrenal function than prednisone 10 mg, as confirmed by ACTH assays.

Children

Clinical application: bronchial asthma

The effectiveness of budesonide has been studied in a large number of studies that have demonstrated the effectiveness of the drug in adults and children when used 1-2 times a day for the prophylactic treatment of persistent asthma.

Clinical application: croup

Several studies have compared budesonide nebulised suspension with placebo in children with croup. Representative examples of studies investigating its use in children with croup are given below.

Effectiveness of use in children with mild to moderate croup

To determine whether budesonide nebulized suspension improves croup symptom scores and reduces the length of hospital stay, a randomized, double-blind, placebo-controlled trial was conducted in 87 children (aged 7 months to 9 years) hospitalized with a clinical diagnosis of croup. Participants received an initial dose of budesonide (2 mg) nebulized suspension or placebo, followed by 1 mg or placebo every 12 hours. Budesonide nebulized suspension significantly improved croup scores at 12 and 24 hours, and at 2 hours in patients with an initial croup symptom score of greater than 3. The length of hospital stay was also reduced by 33%.

A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of budesonide and placebo in 83 infants and children (aged 6 months to 8 years) hospitalized with a clinical diagnosis of croup. Patients received either 2 mg of budesonide nebulized suspension or placebo every 12 hours for up to 36 hours or until discharge. The total croup symptom score was measured before drug administration and at 2, 6, 12, 24, 36, and 48 hours after the initial dose. At 2 hours, the budesonide and placebo groups showed similar improvements in croup symptom scores, with no significant difference between the groups. At 6 hours, the croup symptom score in the budesonide group was significantly better than in the placebo group, and this improvement compared to placebo was equally evident at 12 and 24 hours.

Pharmacokinetics.

Absorption

In adults, the systemic availability of budesonide after administration of the suspension for nebulization via a jet nebulizer is approximately 15% of the nominal dose and 40-70% of the dose administered to the patient. A small part of this amount is due to absorption of the drug that has been swallowed. The maximum plasma concentration (Cmax) is reached approximately 10-30 minutes after the start of nebulization and is approximately 4 nmol/l after a dose of 2 mg.

Distribution

The volume of distribution of budesonide is approximately 3 l/kg body weight. Binding to plasma proteins is on average 85–90%.

Metabolism

Budesonide undergoes extensive (≈90%) first-pass metabolism through the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites of budesonide, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.

The metabolism of budesonide occurs mainly with the participation of the CYP 3A4 enzyme, which belongs to the cytochrome P450 subfamily.

Breeding

Budesonide metabolites are excreted mainly by the kidneys in unchanged or conjugated form. Unchanged budesonide is not detected in the urine. In healthy adult volunteers, the systemic clearance of budesonide is usually high (approximately 1.2 l/min), and the terminal half-life of budesonide after intravenous administration is on average 2–3 hours.

Linearity

The kinetics of budesonide are dose-proportional when used in clinically relevant doses.

Children

In children aged 4–6 years with bronchial asthma, the systemic clearance of budesonide is approximately 0.5 l/min. The clearance in children (per 1 kg of body weight) is approximately 50% higher than in adults. In children with bronchial asthma, the terminal half-life of budesonide after inhalation is approximately 2.3 hours. Approximately the same indicator is observed in healthy volunteers. In children aged 4–6 years with bronchial asthma, the systemic availability of budesonide after administration of the suspension for inhalation via a jet nebulizer (Pari LC Jet Plus with Pari Master compressor) is approximately 6% of the nominal dose and 26% of the dose delivered to the patient. The systemic availability in children is approximately half that in adults.

In children aged 4–6 years with bronchial asthma, Cmax is reached within 20 minutes after the start of nebulization and is approximately 2.4 nmol/l after a dose of 1 mg. Budesonide exposure (Cmax and AUC) after a single dose of 1 mg by nebulization in children aged 4–6 years is comparable to those in healthy adult volunteers who received the same dose of budesonide via the same nebulization system.

Indication

The drug contains a potent non-halogenated corticosteroid - budesonide, intended for the treatment of bronchial asthma in patients for whom the use of inhalers with compressed air atomization of drugs or in the form of a dry powder dosage form is ineffective or impractical.

Budixon Neb is recommended for use in infants and children with croup (a complication of acute viral upper respiratory tract infection, also known as laryngotracheobronchitis or subligamentous laryngitis), which is an indication for hospitalization.

Contraindication

Hypersensitivity to budesonide or to any other component of the drug.

Interaction with other medicinal products and other types of interactions

Limited data on a similar interaction with high doses of inhaled budesonide demonstrate that with concomitant use of itraconazole at a dose of 200 mg once daily, administration of inhaled budesonide (single dose of 1000 mcg) leads to a significant increase in the concentration of the substance in the blood plasma (on average 4-fold).

In women who simultaneously took estrogens or hormonal contraceptives, the concentration of budesonide in the blood plasma increased and the effect of glucocorticosteroids was enhanced, however, when budesonide was used together with low doses of combined oral contraceptives, this effect was absent.

Due to possible suppression of adrenal function, the ACTH stimulation test for the diagnosis of pituitary insufficiency may give false results (low values).

Children

Interaction studies have only been conducted in adult patients.

Application features

Budesonide is not intended for the rapid relief of acute asthma episodes requiring the use of rapid-acting inhaled bronchodilators.

Oral candidiasis may develop during treatment with inhaled corticosteroids. This infection may require the use of appropriate antifungal agents and in some patients it may be necessary to discontinue treatment with inhaled corticosteroids (see section 4.2).

Patients not dependent on steroids. Therapeutic effect is usually achieved within 10 days. Patients with excessive bronchial mucus secretion may initially be given a short (about 2 weeks) additional course of oral corticosteroids. After a course of oral drugs, budesonide as monotherapy may be sufficient treatment.

Patients with steroid dependence. The transition from oral steroids to Budixon Neb can be initiated when the patient is in a relatively stable phase of the disease. Budixon Neb is used in combination with the oral steroid at the dose previously used for approximately 10 days.

The dose of oral steroids should then be gradually reduced (e.g. by 2.5 mg prednisolone or equivalent every month) to the lowest possible level. In many cases, complete replacement of oral steroids with budesonide is possible.

Concomitant use of budesonide with ketoconazole, itraconazole, HIV protease inhibitors and cobicistat-containing products or other potent CYP3A4 inhibitors should be avoided unless the benefit outweighs the increased risk; if the combination cannot be avoided, patients should be monitored for systemic corticosteroid-related side effects. This is of limited clinical significance during short-term (1-2 weeks) treatment with itraconazole or ketoconazole or other potent CYP3A inhibitors, but should be considered during long-term treatment. A reduction in the budesonide dose should also be considered (see section 4.5).

Particular caution should be exercised when switching from oral glucocorticosteroids to inhaled corticosteroids, as there is a risk of transient adrenal insufficiency during this period.

Patients who have required emergency high-dose glucocorticosteroid therapy or long-term treatment with inhaled glucocorticosteroids at the highest recommended dose are also at risk of developing adrenal insufficiency in the event of severe stress. An increase in the dose of oral glucocorticosteroids may be considered in stressful situations or during elective surgery.

Switching from oral glucocorticosteroid therapy to inhaled steroid therapy may result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment should be initiated for these conditions. Usually, insufficient effect of glucocorticosteroid therapy can be suspected if symptoms such as fatigue, headache, nausea, vomiting occur, although this is rare. In such cases, a temporary increase in the dose of oral glucocorticosteroids may sometimes be necessary.

Systemic effects may occur with any inhaled glucocorticosteroid, especially when used at high doses for prolonged periods. The likelihood of such effects is much lower with inhaled corticosteroids than with oral corticosteroids.

Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, glaucoma, and a number of mental and behavioral disorders, including psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression, especially in children (see section 4.8). Therefore, the dose of inhaled glucocorticosteroids should be titrated to the lowest effective dose at which effective control of bronchial asthma is maintained.

As with other inhaled therapies, paradoxical bronchospasm, accompanied by increased wheezing immediately after inhalation, may occur immediately after use of budesonide. If this occurs, treatment with inhaled budesonide should be discontinued immediately and the patient assessed and, if necessary, alternative therapy initiated.

Patients should be advised to seek medical advice if symptoms do not improve with consistent use of the recommended doses.

In case of exacerbation of symptoms, an additional short course of oral glucocorticosteroid therapy should be prescribed.

Impaired hepatic function may affect the elimination of glucocorticosteroids from the body, as the rate of elimination is reduced and systemic exposure is increased. The patient should be warned about the possible development of side effects.

Pneumonia in patients with COPD

There is an increased incidence of pneumonia, including pneumonia requiring hospitalization, in patients with COPD taking inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid doses, but this has not been conclusively proven in all studies.

There is no clear clinical evidence of differences between inhaled corticosteroid-containing products with respect to the risk of pneumonia.

Doctors should monitor patients with COPD especially closely for the development of pneumonia, as the clinical symptoms of these diseases and COPD exacerbations are often similar.

Risk factors for pneumonia in patients with COPD include: current tobacco smoking, older age, low body mass index (BMI), and severe COPD.

Vision impairment

Visual impairment may result from systemic and topical corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, consideration should be given to referral to an ophthalmologist to determine possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which has been observed following systemic and topical corticosteroids.

Children

Effect on growth

Regular monitoring of growth is recommended in children receiving long-term treatment with inhaled corticosteroids. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid to the lowest possible dose at which effective control of bronchial asthma is maintained. The benefits of corticosteroid therapy should be carefully weighed against the possible risk of growth suppression. In addition, it is important to refer the patient for consultation with a pediatric pulmonologist.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Pregnancy

Most results of prospective epidemiological studies and international data obtained in the post-marketing period indicate that treatment with inhaled budesonide during pregnancy did not lead to undesirable effects on the health of the fetus/newborn child. Ensuring appropriate therapy for bronchial asthma is important for both the fetus and the mother. Animal studies have shown that glucocorticosteroids can cause developmental disorders. However, these data are not considered relevant for humans at recommended doses, but therapy with inhaled budesonide should be regularly reviewed and the drug should be used at the lowest effective dose.

The use of budesonide during pregnancy requires careful consideration of the benefits to the woman and the risks to the fetus. Inhaled glucocorticosteroids should be preferred to oral glucocorticosteroids due to the lower systemic effects when used in doses required to achieve the same respiratory response.

Breastfeeding period

Budesonide passes into breast milk. However, when using therapeutic doses of budesonide, no effects on the breast-fed child are expected. Budesonide can be used during breast-feeding.

Maintenance treatment with inhaled budesonide (200 or 400 mcg twice daily) in women with bronchial asthma who are breastfeeding results in only a small systemic exposure of budesonide in breastfed infants.

Given the data on budesonide for inhalation administration and the fact that budesonide exhibits linear PK properties within the therapeutic dose range after nasal, inhalation, oral or rectal administration, it is expected that exposure to budesonide in breast-fed infants at therapeutic doses will be low.

Ability to influence reaction speed when driving vehicles or other mechanisms

Budixon Neb has no or negligible influence on the ability to drive and use machines.

Method of administration and doses

Dosage

The dosage of Budixon Neb should be determined individually. The dose administered to the patient depends on the nebulization equipment used. The nebulization time and the dose delivered depend on the flow rate, the volume of the nebulizer chamber and the filling volume. The air flow rate through the device used for nebulization should be 6–8 liters per minute. The appropriate filling volume for most nebulizers is 2–4 ml. The dose should be reduced to the minimum necessary to maintain adequate control of bronchial asthma. The highest dose (2 mg per day) in children under 12 years of age should be prescribed only in case of severe asthma and for a limited period of time.

Bronchial asthma

If the recommended daily dose of the drug is up to 1 mg, Budixon Neb can be used once a day.

Budixon Neb can be used once a day in patients who have not previously been treated with glucocorticosteroids and in patients in whom the use of inhaled glucocorticosteroids allows for good control of the symptoms of the disease. Budixon Neb can be used once a day in the morning or evening. If the symptoms of the disease worsen, the daily dose of the drug should be increased. When using a daily dose of more than 1 mg, the drug should be administered 2 times a day.

Recommended starting dose

Children

Children aged 6 months to 12 years: the total daily dose is 0.25 to 0.5 mg. In children taking oral glucocorticosteroids, the daily dose can be increased to 1 mg if necessary.

In young children who cannot inhale the product through the adapter, the drug should be administered

using a breathing mask.

Children over 12 years of age: dosage is the same as for adults.

Adults, including the elderly: The total daily dose is 1 to 2 mg twice a day. In very severe cases, the dose may be further increased.

Maintenance dose

It is recommended to use the lowest effective maintenance dose.

Children aged 6 months to 12 years: the total daily dose is 0.25 to 2 mg.

Adults, including elderly patients and children over 12 years of age: the total daily dose is 0.5 to 1 mg twice a day.

Improvement in clinical condition from the use of Budixon Neb can be expected within a few hours of starting treatment.

Budixon Neb is intended for long-term treatment; however, it does not provide rapid relief of symptoms of acute asthma attacks in which rapid-acting bronchodilators are indicated.

For patients who require an increase in the dose of glucocorticosteroids to improve the effectiveness of treatment, it is usually recommended to increase the dose of Budixon Neb instead of introducing oral glucocorticosteroids due to the lower risk of systemic side effects.

Patients taking oral glucocorticosteroids

Once adequate asthma control has been achieved, the use of Budixon Neb allows for the replacement or significant reduction of the dose of oral glucocorticosteroids. When changing treatment from oral glucocorticosteroids to treatment with Budixon Neb, the patient's condition should be stable. It is recommended to take high doses of Budixon Neb for 10 days in combination with the previously used oral glucocorticosteroid at the same dose.

The oral dose of glucocorticosteroids should then be gradually reduced (e.g. by approximately 2.5 mg prednisolone or equivalent dose of other glucocorticosteroids per month) to the lowest dose that maintains control of symptoms. Oral glucocorticosteroids can often be completely replaced by Budixon Neb. For further information on stopping glucocorticosteroids, see section 4.4.

Budesonide in the form of a nebulizer suspension, after administration by the patient, enters the lungs during breathing. It is very important that the patient breathes calmly and evenly through the nebulizer adapter or breathing mask.

Croup

The usual dose for infants and children with croup is 2 mg of budesonide in nebulized form. This dose can be taken as a single dose or divided into two doses of 1 mg taken 30 minutes apart. This dosing regimen can be repeated every 12 hours for a maximum of 36 hours or until a therapeutic effect is achieved.

Patients with renal or hepatic insufficiency

Kidney or liver. Budesonide is metabolized mainly in the liver, so in patients with severe cirrhosis of the liver, an increase in its serum level may occur. There is no need to adjust the dose of Budexon Neb in patients with impaired renal function.

Method of application.

Budixon Neb suspension for spraying should be used using a nebulizer with an adapter or a breathing mask.

In order to minimize the risk of candidiasis in the oral cavity and throat, the patient should rinse his mouth with water after each inhalation.

The patient should also be advised to always rinse their face with water after using the nebulizer with a breathing mask to prevent facial irritation.

Ultrasonic nebulizers should not be used as they do not provide adequate budesonide dosage.

The nebulizer and compressor should produce droplets with a diameter of 3 to 5 mm.

The dose of budesonide that the patient receives is from 11 to 22% of the dose contained in the nebulizer and depends on:

nebulization time,

chamber volume,

technical properties of the compressor and nebulizer (nebulization kit),

the patient's tidal volume,

using an adapter or breathing mask.

In order to receive the maximum dose of budesonide, it is necessary to ensure an adequate nebulizer throughput (from 6 to 8 l/min). The chamber volume should be from 2 to 6 ml.

For younger children, a breathing mask that fits snugly around the face should be used to ensure the delivery of the maximum amount of budesonide.

Before opening, the plastic container containing the drug should be shaken thoroughly.

The nebulizer chamber should be washed after each use. The chamber and mask should be washed with warm water and a mild detergent, then rinsed thoroughly with water and dried, connected to the compressor. Before using the nebulizer, it is necessary to read the manufacturer's instructions for using the nebulizer.

Budixon Neb can be mixed with 0.9% sodium chloride solution and with solutions of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglicate or ipratropium bromide.

The suspension contained in the plastic container can be divided to obtain

appropriate dose of the active substance.

The opened plastic container should be stored in an aluminum envelope away from light.

The resulting mixture should be used within 30 minutes.

Dosage recommendations

Table 1

Children.

Budikson Neb should be used in children according to indications (see sections “Indications” and “Features of use”).

Overdose

Acute overdose of Budixon Neb should not pose a clinically significant problem even when excessive doses are used.

The drug contains 0.1 mg/ml of disodium edetate, which has been shown to cause bronchoconstriction if its level exceeds 1.2 mg/ml.

Side effects

The following side effects are classified according to frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency unknown (frequency cannot be estimated from the available data).

* See below for a description of specific adverse reactions; facial skin irritation.

** Applies to children and young people, see below.

*** Based on frequency reported in clinical trials.

Description of selected adverse reactions

Occasionally, hypersensitivity reactions in the form of facial skin irritation have been reported when using a nebulizer with a breathing mask. To prevent irritation, wash your face after each use of the breathing mask.

There is an increased risk of pneumonia in patients with newly diagnosed COPD who are initiated on inhaled corticosteroids. However, a weighted evaluation of eight pooled clinical trials involving 4643 patients with COPD treated with budesonide and 3643 patients randomized to treatment without inhaled corticosteroids did not demonstrate an increased risk of pneumonia. The results of the first seven of these eight trials were published as a separate meta-analysis.

Oropharyngeal candidiasis is a potential risk due to drug deposition. The patient should be instructed to rinse the mouth with water after each maintenance dose inhalation to minimize this risk.

As with any inhalation therapy, the development of paradoxical bronchospasm is very rare (see section "Special warnings and precautions for use").

In placebo-controlled clinical trials, cataracts were uncommonly reported, also in the placebo group.

A pooled analysis of clinical trials involving 13,119 patients treated with inhaled budesonide and 7,278 patients treated with placebo was performed. The incidence of anxiety was 0.52% in the inhaled budesonide group and 0.63% in the placebo group. The incidence of depression was 0.67% in the inhaled budesonide group and 1.15% in the placebo group.

Systemic effects may occur with inhaled glucocorticosteroids, which are likely to depend on dose, exposure time, concomitant and previous corticosteroid treatment, and individual sensitivity.

Effects on growth in children

In children receiving long-term treatment with inhaled corticosteroids, regular monitoring of growth is recommended. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid. The benefits of glucocorticosteroid therapy should be carefully weighed against the possible risk of growth suppression. In addition, it is important to refer the patient for consultation with a pediatric pulmonologist.

Children

Due to the risk of growth retardation in children, growth monitoring is necessary.

Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.

Expiration date

36 months.

Once the envelope is opened, the containers contained therein should be used within

3 months. After reconstitution or dilution, the suspension must be used within 30 minutes.

Storage conditions

Store below 30°C out of the reach of children. Do not freeze. Store in the original packaging and in an envelope to protect from light.

Packaging

2 ml in a container; 5 containers in an envelope; 4 envelopes together with instructions for medical use in a cardboard box.

Vacation category

According to the recipe.

Producer

Adamed Pharma JSC, Poland.

Location of the manufacturer and address of the place of production