Budesonide-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Budesonid-Darnytsia (Budesonid-Darnytsia)

Composition:

active substance: budesonide;

1 ml of nebulizer suspension contains 0.25 mg or 0.5 mg of budesonide;

excipients: disodium edetate, sodium chloride, polysorbate 80, anhydrous citric acid, sodium citrate, water for injections.

Pharmaceutical form. Nebulizer suspension.

Main physicochemical characteristics: white homogeneous suspension.

Pharmacotherapeutic group. Inhalation agents used in the treatment of obstructive respiratory diseases. Glucocorticoids. ATC code R03BA02.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Budesonide is a glucocorticosteroid with potent local anti-inflammatory activity.

The precise mechanism of action of glucocorticosteroids in the treatment of bronchial asthma has not been fully elucidated. It is believed that important anti-inflammatory effects include suppression of inflammatory mediator release and inhibition of cytokine-mediated immune responses. The activity of budesonide, as determined by its affinity for glucocorticosteroid receptors, is approximately 15 times greater than that of prednisolone.

Clinical Efficacy

Budesonide exerts anti-inflammatory effects that reduce bronchial obstruction in both early and late phases of the allergic reaction. Budesonide reduces the reactivity to histamine and methacholine in patients with hyperresponsive airways.

Studies have demonstrated that the earlier budesonide treatment is initiated following the onset of a bronchial asthma attack, the better the expected lung function outcome.

Clinical Safety Data

Effect on Plasma Cortisol Concentration:

In studies involving healthy volunteers, dose-dependent reductions in plasma and urinary cortisol levels were observed with budesonide administration. At recommended doses, budesonide has a significantly lower effect on adrenal function than 10 mg prednisolone, as demonstrated by adrenocorticotropic hormone (ACTH) stimulation tests.

Children

Clinical Efficacy in Bronchial Asthma

The efficacy of budesonide suspension for nebulization has been evaluated in numerous studies, which demonstrated the effectiveness of the drug when administered once or twice daily for the treatment of persistent bronchial asthma in both adults and children. Several examples of representative studies are provided below.

In children aged 3 years and older, no systemic effects were observed with budesonide doses up to 400 mcg/day. At doses of 400–800 mcg/day, biochemical signs of systemic effects may occur, while such signs are common at daily doses exceeding 800 mcg. This information pertains to budesonide administered as an inhalation spray and inhalation powder.

Bronchial asthma, as well as the use of inhaled corticosteroids, may cause growth retardation. Limited long-term data suggest that most children and adolescents receiving inhaled budesonide therapy ultimately achieve their target adult height. However, an initial, small, but transient reduction in growth velocity (approximately 1 cm) is observed, typically during the first year of treatment.

Exercise-induced Bronchial Asthma

Inhaled budesonide therapy is effective in preventing asthma symptoms triggered by physical exertion.

Clinical Use: Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

Several studies of budesonide suspension for nebulization at doses of 4–8 mg/day have demonstrated efficacy in the treatment of COPD exacerbations.

The efficacy of budesonide suspension for nebulization was evaluated in an open-label, randomized, comparative study involving 78 hospitalized patients with COPD exacerbations assigned to two parallel groups: budesonide suspension for nebulization (n = 37) at 4 mg/day (2 mg twice daily) or intravenous prednisolone at 120–180 mg/day (n = 41) for 7–14 days. In both groups, similar improvements were observed in forced expiratory volume in one second (FEV₁), oxygen saturation measured by pulse oximetry (SpO₂), and symptoms (COPD Assessment Test™ (CAT)).

In a multicenter, randomized, controlled, single-blind study involving 471 patients with COPD exacerbations, budesonide suspension for nebulization at 6 mg/day (2 mg three times daily) was compared to intravenous methylprednisolone (40 mg/day) for 10 days. Clinical efficacy of budesonide suspension for nebulization compared to systemic methylprednisolone, measured by FEV₁, arterial partial pressure of CO₂ (PaCO₂), and symptoms (CAT score), was comparable, while arterial partial pressure of O₂ (PaO₂) showed greater improvement in the methylprednisolone group.

In a double-blind, randomized, placebo-controlled study involving 199 patients with COPD exacerbations, budesonide suspension for nebulization at 8 mg/day (2 mg four times daily, (n = 71)), oral prednisolone 30 mg every 12 hours (n = 62), or placebo (n = 66) were administered for 3 days. The improvement in post-bronchodilator FEV₁ compared to placebo was 0.10 L for budesonide and 0.16 L for prednisolone; the difference between the two active treatment groups was not statistically significant. The proportion of patients achieving a clinical improvement in post-bronchodilator FEV₁ of at least 0.15 L was higher in the budesonide group (34%) and the prednisolone group (48%) compared to placebo (18%). Differences were statistically significant for both active treatment groups compared to placebo (p < 0.05), but not between the active treatment groups.

Clinical Use: Croup

Studies in children with croup compared budesonide treatment to placebo. Representative studies evaluating budesonide for the treatment of croup in children are described below.

Efficacy in Children with Mild to Moderate Croup

To determine whether budesonide has a positive effect on croup symptoms and reduces hospitalization duration, a randomized, double-blind, placebo-controlled study 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) or placebo, followed by budesonide 1 mg or placebo every 12 hours. Budesonide significantly improved croup symptom scores at 12 and 24 hours, and at 2 hours in patients with an initial symptom score above 3 points. Hospitalization duration was also reduced by 33%.

Efficacy in Children with Moderate to Severe Croup

A randomized, double-blind, placebo-controlled study was conducted in 83 infants and children (aged 6 months to 8 years) hospitalized with croup to compare the efficacy of budesonide versus placebo. Patients received budesonide 2 mg or placebo every 12 hours for up to 36 hours or until discharge. Total croup symptom scores were assessed before dosing and at 0, 2, 6, 12, 24, 36, and 48 hours after the initial dose. At 2 hours, both budesonide and placebo groups showed similar improvement in croup symptom scores, with no statistically significant difference between groups. At 6 hours, the croup symptom score in the budesonide group was significantly better than in the placebo group, and this improvement remained statistically significant at 12 and 24 hours.

Preclinical Safety Data

Acute, subacute, and chronic toxicity studies indicated that the systemic effects of budesonide are less pronounced or similar to those of other glucocorticosteroids, including reduced body weight gain, lymphoid tissue atrophy, and adrenal cortex atrophy.

Budesonide showed no mutagenic or clastogenic potential in six standard genotoxicity tests.

In a carcinogenicity study conducted in male rats, an increased incidence of brain gliomas was observed. However, these findings were not confirmed in two subsequent studies, in which the incidence of gliomas in animals treated with budesonide, prednisolone, or triamcinolone acetonide was comparable to that in control groups.

In carcinogenicity studies in male rats, an increased incidence of primary hepatocellular liver tumors was also observed. These findings were confirmed in another study in which animals were administered budesonide and reference glucocorticosteroids. These effects are likely due to glucocorticosteroid receptor activity and are typical of this pharmacological class.

Clinical experience has not revealed evidence of an association between budesonide or other glucocorticosteroid use and the development of cerebral gliomas or primary hepatocellular tumors in humans.

Pharmacokinetics

Absorption

In adults, the systemic bioavailability of budesonide after administration as a nebulized suspension via a jet nebulizer is approximately 15% of the nominal dose and 40–70% of the dose delivered to the patient. A minor portion of this amount results from drug swallowed and absorbed. Maximum plasma concentration is reached approximately 10–30 minutes after the start of nebulization and is about 4 nmol/L following a 2 mg dose.

Distribution

The volume of distribution of budesonide is approximately 3 L/kg. Plasma protein binding is on average 85–90%.

Metabolism

Budesonide undergoes extensive first-pass metabolism in the liver (≈90%) into metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide. Budesonide metabolism is primarily mediated by CYP3A enzymes of the cytochrome P450 subfamily.

Elimination

Budesonide metabolites are excreted predominantly by the kidneys, either unchanged or in conjugated form. Unchanged budesonide is not detected in urine. In healthy adults, systemic clearance of budesonide is typically high (approximately 1.2 L/min), and the terminal half-life after intravenous administration averages 2–3 hours.

Linearity/Non-linearity

Budesonide kinetics are dose-proportional following administration in clinically relevant doses.

Pharmacokinetic/Pharmacodynamic Relationship

Children

In children aged 4–6 years with bronchial asthma, systemic clearance of budesonide is approximately 0.5 L/min. Clearance per kg body weight in children is about 50% higher than in adults. In children with bronchial asthma, the terminal half-life of budesonide after inhalation is approximately 2.3 hours, similar to that observed in healthy adults. In patients aged 4–6 years with bronchial asthma, systemic bioavailability of budesonide after administration of nebulized suspension is approximately 6% of the nominal dose and 26% of the dose delivered to the patient. Systemic bioavailability in children is approximately half that in healthy adults.

In children aged 4–6 years with bronchial asthma, maximum plasma concentration is reached within 20 minutes after the start of nebulization and is approximately 2.4 nmol/L following a 1 mg dose.

Exposure parameters of budesonide (C_max and AUC) after a single 1 mg dose administered by nebulization in children aged 4–6 years are comparable to those in healthy adults receiving the same dose via the same nebulization system.

The pharmacokinetics of budesonide in patients with impaired renal function are unknown. The effect of budesonide may be enhanced in patients with hepatic disease.

Clinical characteristics.

Indications.

The medicinal product Budenoside-Darnitsya, suspension for nebulization, is indicated for patients with:

• bronchial asthma;
• acute exacerbation of chronic obstructive pulmonary disease in individuals without signs of acute respiratory failure;
• severe pseudocroup (subglottic laryngitis) requiring hospitalization.

This medicinal form is suitable for patients who have difficulty using devices such as aerosol or powder inhalers for drug administration.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product Budenoside-Darnitsya.

Interaction with other medicinal products and other types of interactions.

Metabolism of budesonide is primarily mediated by the CYP3A4 enzyme. Therefore, concomitant use of inhibitors of this enzyme, such as ketoconazole, itraconazole, and HIV protease inhibitors, may result in several-fold increase in systemic exposure to budesonide (see section "Special precautions for use"). Since data on dosage recommendations for such combinations are lacking, they should be avoided. If avoidance is not possible, the interval between administration of the medicinal products should be as long as possible, and consideration may be given to reducing the dose of budesonide.

Limited data on this interaction with high doses of inhaled budesonide show that concomitant administration of itraconazole 200 mg once daily with inhaled budesonide (single dose 1000 mcg) leads to a significant increase in plasma concentration of the substance (on average, 4 times).

Increased plasma concentrations and enhanced effect of corticosteroids have been observed in women receiving estrogens or oral contraceptives. However, no significant changes were noted with concomitant use of budesonide and low-dose combined oral contraceptives.

Since adrenal function may be suppressed, an ACTH stimulation test, intended for diagnosis of pituitary insufficiency, may yield false results (low values).

Special precautions for use.

General information

Budesonide is not intended for rapid relief of acute asthma attacks when inhaled short-acting bronchodilators are required.

Patients should be advised to consult a physician if the overall effectiveness of treatment decreases, as repeated inhalations during severe asthma attacks should not delay the initiation of other essential therapies. In case of a sudden worsening of condition, treatment should be supplemented with short-term oral corticosteroids.

Transition from oral corticosteroids

Particular caution is required when treating patients transitioning from oral corticosteroids, as they may remain at risk of adrenal insufficiency for a prolonged period. Patients who have required emergency treatment with high-dose corticosteroids or long-term treatment with the highest recommended doses of inhaled corticosteroids may also belong to this risk group. Signs and symptoms of adrenal insufficiency may manifest under conditions of severe stress in such patients. During periods of stress or planned surgical procedures, consideration should be given to the possible need for additional systemic corticosteroids in these patients.

During transition from oral corticosteroid therapy to the medicinal product Budesonide-Darnitsya, patients may experience symptoms such as muscle and joint pain. In such cases, a temporary increase in the dose of oral corticosteroid may be necessary. If fatigue, headache, nausea, vomiting, or similar symptoms occur intermittently, inadequate corticosteroid effect should be suspected in most cases.

Systemic effects of inhaled corticosteroids

Systemic effects of inhaled corticosteroids may occur, particularly when administered at high doses over a prolonged period. These effects are considerably less likely 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, cataract, glaucoma, and less frequently, a range of psychological or behavioral effects such as psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression (particularly in children). Therefore, it is important that the dose of inhaled corticosteroid is reduced to the lowest level at which effective control of bronchial asthma is maintained.

Switching from systemic corticosteroid therapy to the medicinal product Budesonide-Darnitsya may occasionally lead to the emergence of allergic conditions previously controlled by systemic treatment, such as rhinitis and eczema.

Concomitant use with other medicinal products

Concomitant use of the medicinal product with ketoconazole, itraconazole, HIV protease inhibitors, or other potent CYP3A4 inhibitors should be avoided. If concomitant use cannot be avoided, the interval between administration of these medicinal products should be as long as possible (see also section "Interaction with other medicinal products and other forms of interaction").

Bronchospasm

As with other inhaled medications, paradoxical bronchospasm with immediate increase in wheezing may occur after dosing. In such cases, treatment with inhaled budesonide should be discontinued immediately, the patient's condition assessed, and alternative therapy initiated if necessary.

Use in patients with renal impairment

Impaired liver function affects the body's ability to eliminate corticosteroids, leading to reduced clearance of the drug and development of high systemic exposure. The potential for systemic adverse effects should be kept in mind.

Effect on growth

In children receiving long-term corticosteroid treatment, regardless of the formulation used, regular monitoring of growth is recommended. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of inhaled corticosteroid. The benefits of corticosteroid treatment should be weighed against the potential risk of growth retardation. In addition, referral of the patient to a pediatric pulmonologist may be appropriate.

Oropharyngeal candidiasis

Oropharyngeal candidiasis may develop during treatment with inhaled corticosteroids. The appearance of this infection may require treatment with appropriate antifungal medicinal products, and in some patients, discontinuation of therapy may be necessary (see section "Dosage and administration").

Respiratory tract infections

Particular caution is required in patients with active pulmonary tuberculosis or latent tuberculosis, as well as in patients with fungal or viral respiratory tract infections.

Pneumonia in patients with COPD

An increased incidence of pneumonia, including pneumonia requiring hospitalization, has been observed in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with higher corticosteroid doses, although this has not been definitively demonstrated in any study.

There are no conclusive clinical data demonstrating within-class differences among inhaled corticosteroid medicinal products regarding the magnitude of pneumonia risk.

Physicians should be vigilant for possible development of pneumonia in COPD patients, as the clinical signs of this infection may overlap with symptoms of COPD exacerbation.

Risk factors for pneumonia in COPD patients include smoking, advanced age, low body mass index (BMI), and severe COPD.

Visual disturbances

Visual disturbances may occur during systemic or local use of corticosteroids. Patients experiencing symptoms such as blurred vision or other visual disturbances should seek ophthalmological consultation to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSC), which has been reported after systemic or local corticosteroid use.

Use during pregnancy or breastfeeding.

Pregnancy

Most prospective epidemiological studies and worldwide post-marketing data have not demonstrated an increased risk of adverse effects on the fetus or newborn associated with the use of inhaled budesonide during pregnancy. It is important for both the fetus and the pregnant woman to maintain adequate asthma control during pregnancy. As with any medicinal product used during pregnancy, the benefits of budesonide use for the mother should be weighed against potential risks to the fetus.

Animal studies have shown that glucocorticoids may cause developmental abnormalities; however, these findings are not considered relevant to humans when used at recommended doses.

Animal studies have also shown that excess prenatal glucocorticoids may increase the risk of intrauterine growth retardation, cardiovascular disease in adulthood, and permanent changes in glucocorticoid receptor density, neurotransmitter metabolism, and behavior, even at doses below teratogenic levels.

During pregnancy, the lowest effective dose of budesonide should be used, taking into account the risk of worsening asthma control.

Breastfeeding

Budesonide passes into breast milk. However, when therapeutic doses of the medicinal product Budesonide-Darnitsya are used, no effect on the breastfed infant is expected, as systemic exposure to the infant is negligible. The medicinal product Budesonide-Darnitsya can be used during breastfeeding.

Ability to affect reaction speed when driving vehicles or operating machinery.

Budesonide-Darnitsya does not affect the ability to drive vehicles or operate machinery.

Administration and Dosage

Dosage in bronchial asthma

The dosage of the medicinal product Budesonide-Darnytsia must be adjusted according to individual patient needs. If the daily dose does not exceed 1 mg, the entire dose may be administered once daily. If higher daily doses are required, the dose should be divided into two administrations per day. The highest dose (2 mg per day) should be prescribed to children only in cases of severe asthma and for a limited period of time. The maintenance dose should be the lowest effective dose.

Initial dosage:

Children aged 6 months and older: 0.25–0.5 mg per day. If necessary, the dose may be increased up to 1 mg per day.

Adults: 1–2 mg per day.

For maintenance therapy:

Children aged 6 months and older: 0.25–2 mg per day.

Adults: 0.5–4 mg per day. In very severe cases, the dose may be further increased.

When treating patients with bronchial asthma in whom it is desirable to enhance the therapeutic effect, increasing the dose of the medicinal product Budesonide-Darnytsia is preferred over combined therapy with oral corticosteroids, due to the lower risk of systemic adverse effects.

Treatment with the medicinal product Budesonide-Darnytsia allows replacement or substantial reduction of oral corticosteroid dosage while maintaining asthma control. When switching from oral corticosteroids to Budesonide-Darnytsia, the patient should be in a relatively stable condition. Thereafter, for 10 days, a high dose of the medicinal product Budesonide-Darnytsia should be administered in combination with the previously used dose of oral corticosteroid.

After this period, the dose of oral corticosteroid should be gradually reduced, for example by 2.5 mg/month of prednisolone or equivalent per month, down to the lowest possible level. In many cases, oral corticosteroid can be completely replaced by the medicinal product Budesonide-Darnytsia. For additional information on discontinuation of oral corticosteroids, see section "Special precautions for use".

Time to onset of effect in bronchial asthma

After administration of the initial dose, effect may be expected within several hours. Full therapeutic effect is achieved only after several weeks of treatment.

Dosage in acute exacerbation of COPD

Patients should be treated with a daily dose of 4–8 mg of the medicinal product Budesonide-Darnytsia, suspension for nebulization, divided into 2–4 doses, until clinical improvement is achieved, but not longer than 10 days.

The use of nebulized budesonide has not been evaluated in clinical studies involving patients with acute exacerbation of COPD and respiratory failure requiring invasive mechanical ventilation or hospitalization in intensive care units.

Time to onset of effect in acute exacerbation of COPD

After inhalation of the medicinal product Budesonide-Darnytsia, suspension for nebulization, for treatment of COPD exacerbations, the time to symptom improvement is comparable to that with systemic corticosteroids.

Dosage in croup

For children with croup, the usual dose is 2 mg of nebulized budesonide. This dose should be administered either as a single dose or as two doses of 1 mg each, given 30 minutes apart. Administration of the medicinal product may be repeated every 12 hours, up to a total of 36 hours or until clinical improvement occurs.

For children unable to inhale via a mouthpiece, a face mask may be used.

General information

Impaired liver or kidney function

Experience in treating patients with impaired hepatic or renal function is lacking. Since budesonide is primarily eliminated via hepatic metabolism, increased exposure may be expected in patients with severe hepatic cirrhosis.

Table 1

Dosage recommendations

Dose (mg)	Volume of medicinal product Budesonide-Darnytsia, suspension for nebulization
	0.25 mg/ml	0.5 mg/ml
0.25	1 ml*	-
0.5	2 ml	-
0.75	3 ml	-
1	-	2 ml
1.5	-	3 ml
2	-	4 ml
4	-	8 ml

*The medication should be mixed with 0.9% physiological saline solution to achieve a volume of 2 mL.

Method of Administration

Instructions for the correct use of the medicinal product Budesonide-Darnitsya, suspension for nebulization.

Budesonide-Darnitsya, suspension for nebulization, should be inhaled using a jet nebulizer with a mouthpiece or an appropriate face mask.

It is important that the patient breathes calmly and evenly through the nebulizer mouthpiece, as budesonide, when used in the form of the medicinal product Budesonide-Darnitsya, suspension for nebulization, reaches the lungs during inhalation.

After inhalation, patients should rinse their mouth with water to minimize the risk of oropharyngeal candidiasis.

NOTE! It is important to instruct the patient/caregiver to wash the face skin with water after using a face mask to prevent skin irritation.

Ultrasonic nebulizers should not be used, as they deliver a very low dose of budesonide to the patient. The nebulizer and compressor (pump unit) should be set so that most of the delivered liquid particles are within the range of 3–5 μm.

The airflow rate through the nebulizer is also important. To achieve the maximum possible dose of budesonide, the airflow rate should be 5–8 L/min. The filling volume should be 2–4 mL. The delivered dose for children is maximized by using a face mask that fits snugly against the face.

Before opening the single-dose container, it should be gently shaken.

The nebulizer chamber must be cleaned after each use. Rinse the chamber, mouthpiece, or face mask with warm running water and use a mild detergent.

Rinse thoroughly and dry the chamber by connecting it to the compressor or air outlet.

See also the nebulizer manufacturer's instructions.

Instructions for Use and Handling

Budesonide-Darnitsya, suspension for nebulization, may be mixed with sodium chloride 9 mg/mL (0.9%) solution and/or with nebulizer solutions containing terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglicate, or ipratropium bromide. The mixture should be used within 30 minutes.

Any unused medicinal product or waste material should be disposed of in accordance with national requirements.

Children.

Budesonide-Darnitsya medicinal product should be administered to children as indicated (see sections "Indications" and "Dosage and Administration").

Overdose.

Acute overdose of Budesonide-Darnitsya suspension for nebulization, even with excessive doses, is unlikely to cause clinically significant problems. However, prolonged use of high doses may lead to systemic glucocorticosteroid effects such as hypercorticism and suppression of adrenal gland function.

Adverse Reactions

All adverse reactions are listed by system organ class and frequency: 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 the available data).

Eye disorders:
Uncommon – cataract***, blurred vision (see also section "Special precautions"); frequency not known – glaucoma.

Respiratory, thoracic and mediastinal disorders:
Common – cough, throat irritation; rare – bronchospasm, dysphonia, hoarseness.

Endocrine disorders:
Rare – signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation**.

Nervous system disorders:
Uncommon – tremor.

Psychiatric disorders:
Uncommon – anxiety, depression; rare – restlessness, nervousness, behavioural changes (mainly in children).

Immune system disorders:
Rare – immediate and delayed hypersensitivity reactions*, including rash, contact dermatitis, urticaria, angioedema, and anaphylactic reaction.

Skin and subcutaneous tissue disorders:
Rare – bruising.

Musculoskeletal and connective tissue disorders:
Uncommon – muscle spasms.

Infections and infestations:
Common – oral and pharyngeal candidiasis, pneumonia (in patients with COPD).

* Facial skin irritation, see below.

** Refers to "Paediatric population", see below.

*** See section "Eye disorders" below.

Occasionally, when using inhaled glucocorticosteroids, signs or symptoms of systemic glucocorticosteroid side effects may occur, likely dependent on dose, duration of exposure, concomitant and prior corticosteroid use, and individual sensitivity.

Immune system disorders

Occasionally, when a nebulizer with a face mask was used, facial skin irritation as a hypersensitivity reaction has been reported. To prevent irritation, the face should be washed with water after each use of the mask.

Infections and infestations

Due to the risk of candidiasis of the mouth and throat, patients should rinse their mouth with water after each inhalation.

Eye disorders

In placebo-controlled studies, cataract was reported as an uncommon adverse reaction in both the active treatment and placebo groups.

Psychiatric disorders

In pooled clinical trial data, 13,119 patients received inhaled budesonide and 7,278 received placebo. The incidence of anxiety was 0.52% with inhaled budesonide and 0.63% with placebo; the incidence of depression was 0.67% with inhaled budesonide and 1.15% with placebo.

Paediatric population

Due to the risk of growth retardation in children, growth parameters should be monitored regularly (see section "Special precautions").

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals, patients, and their legal representatives should report all suspected adverse reactions and/or lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Keep containers in the pouch to protect from light.

Keep out of reach and sight of children.

After opening the pouch, the single-dose containers contained within should be used within 3 months.

After opening a single-dose container, the suspension should be used within 12 hours.

Packaging.

Nebuliser suspension 0.25 mg/ml, 0.5 mg/ml; 2 ml in a single-dose container; 5 single-dose containers in a pouch; 4 pouches in a carton.

Prescription status. Prescription only.

Manufacturer.

Genetic S.p.A.

Manufacturer's address.

Contrada Canfora, Fisciano, 84084, Italy

Marketing Authorisation Holder.

JSC "Pharmaceutical Company "Darnytsia"

Address of the Marketing Authorisation Holder.

13 Borospilska Street, Kyiv, 02093, Ukraine