Pulmicort

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PULMICORT (PULMICORT®)

Composition:

Active substance: budesonide;

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

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

Pharmaceutical form. Nebulizer suspension.

Main physicochemical characteristics: a readily resuspendable white or almost white suspension, filled into single-dose plastic containers.

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

Pharmacological Properties

Pharmacodynamics

Mechanism of action

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

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

Clinical efficacy

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

Studies have demonstrated that the earlier budesonide treatment is initiated after the onset of an asthma attack, the greater the expected improvement in lung function.

Clinical safety data

Effect on plasma cortisol concentration:

In studies involving healthy volunteers, administration of Pulmicort Turbuhaler resulted in a dose-dependent reduction in plasma and urinary cortisol levels. At recommended doses, Pulmicort Turbuhaler has a significantly smaller 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 Pulmicort nebulizer suspension has been studied in numerous trials, which demonstrated the effectiveness of the medicinal product when administered once or twice daily in the treatment of persistent bronchial asthma in adults and children. Several examples of representative studies are provided below.

In children aged 3 years and older, no systemic effects were observed at 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 applies to the medicinal product Pulmicort 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 indicate that most children and adolescents receiving inhaled budesonide therapy ultimately achieve their target adult height. However, there is an initial, small, but transient reduction in growth velocity (approximately 1 cm), typically occurring during the first year of treatment.

Exercise-induced asthma

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

Clinical use: acute exacerbations of chronic obstructive pulmonary disease (COPD)

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

The efficacy of budesonide was evaluated in an open-label, randomized, comparative study involving 78 hospitalized patients with COPD exacerbations assigned to two parallel groups receiving either budesonide nebulizer suspension (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 patients receiving either budesonide nebulizer suspension or prednisolone, similar improvements were observed in forced expiratory volume in one second (FEV1), blood oxygen saturation measured by pulse oximetry (SpO2), and symptoms (COPD Assessment TestTM (CAT)).

In a multicenter, randomized, controlled, single-blind study involving 471 patients with COPD exacerbations, budesonide nebulizer suspension at 6 mg/day (2 mg three times daily) or intravenous methylprednisolone (40 mg/day) was administered for 10 days. The clinical efficacy of budesonide nebulizer suspension compared to systemic methylprednisolone, measured by FEV1, arterial partial pressure of CO2 (PaCO2), and symptoms (CAT), 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 nebulizer suspension at 8 mg/day (2 mg four times daily, (n = 71)), 30 mg oral prednisolone 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 with clinical improvement in post-bronchodilator FEV1 of at least 0.15 L was higher in the budesonide nebulizer suspension group (34%) and the prednisolone group (48%) than in the placebo group (18%). The 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

Several studies in children with croup have compared treatment with Pulmicort to placebo.

Representative studies evaluating the use of Pulmicort in the treatment of children with croup are described below.

Efficacy in children with mild to moderate croup

To determine whether Pulmicort has a positive effect on croup symptoms and whether this treatment 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 Pulmicort (2 mg) or placebo, followed by doses of Pulmicort 1 mg or placebo every 12 hours. Pulmicort significantly improved croup symptom scores at 12 and 24 hours, and at 2 hours in patients with initial croup symptom scores above 3 points. Hospitalization duration was also reduced by 33%.

Efficacy in children with moderate to severe croup

To compare the efficacy of Pulmicort and placebo, a randomized, double-blind, placebo-controlled study was conducted in 83 infants and children (aged 6 months to 8 years) hospitalized with a clinical diagnosis of croup. Patients received Pulmicort 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 the Pulmicort and placebo groups showed similar improvement in croup symptom scores, with no statistically significant difference between groups. At 6 hours, croup symptom scores in the Pulmicort group were statistically significantly better than in the placebo group, and this improvement compared to placebo remained evident at 12 and 24 hours.

Pharmacokinetics

Absorption

In adults, the systemic bioavailability of budesonide after administration of Pulmicort nebulizer suspension via 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 is due to absorption of the drug that has been swallowed. Maximum plasma concentration is reached approximately 10–30 minutes after the start of nebulization and is approximately 4 nmol/L after a 2 mg dose.

Distribution

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

Metabolism

Budesonide undergoes extensive (~90%) first-pass metabolism in the liver to metabolites with low glucocorticoid activity. The glucocorticoid activity of the main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% 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 in unchanged or conjugated forms. 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 elimination half-life of budesonide after intravenous administration averages 2–3 hours. Budesonide pharmacokinetics are dose-proportional when administered at clinically relevant doses.

Linearity/non-linearity

Budesonide kinetics are dose-proportional at 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 in children (per kg body weight) is approximately 50% higher than in adults. In children with bronchial asthma, the terminal elimination 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 Pulmicort nebulizer suspension via jet nebulizer (Pari LC Jet Plus® with Pari Master® compressor) is approximately 6% of the nominal dose and 26% of the delivered dose. 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 after a 1 mg dose.

Exposure parameters of budesonide (Cmax 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 delivered dose of budesonide via the same nebulization system.

The pharmacokinetics of budesonide in patients with renal impairment are unknown. The effect of budesonide may be increased in patients with hepatic disease.

Clinical characteristics.

Indications.

The medicinal product Pulmicort, 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 croup (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 Pulmicort.

Interaction with other medicinal products and other types of interactions.

Metabolism of budesonide is primarily mediated by the enzyme CYP3A4. Therefore, concomitant use of inhibitors of this enzyme, such as ketoconazole, itraconazole, and HIV protease inhibitors, may result in several-fold increases in systemic exposure to budesonide (see section "Special precautions for use"). Since data on dosage recommendations are lacking, such combinations should be avoided. If avoidance is not possible, the interval between administration of the medicinal products should be as long as possible, and consideration should 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 by 4 times).

Increased plasma concentrations and enhanced corticosteroid effects 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 initiation of other essential therapy. In case of sudden worsening of symptoms, treatment should be supplemented with short-term oral corticosteroids.

Transition from oral corticosteroids

Particular caution is required when treating patients switching 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. During periods of stress or elective surgery, such patients may exhibit signs and symptoms of adrenal insufficiency. Additional systemic corticosteroids should be considered for these patients during stressful situations or surgical procedures.

During transition from oral corticosteroid therapy to Pulmicort, patients may experience symptoms such as muscle and joint pain. In such cases, a temporary increase in the dose of oral corticosteroid may be required. If fatigue, headache, nausea, vomiting, or similar symptoms occur intermittently, corticosteroid insufficiency should be suspected in most cases.

Systemic effects of inhaled corticosteroids

Systemic effects of inhaled corticosteroids may occur, particularly with long-term use of high doses. 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 disturbances, anxiety, depression, or aggression (particularly in children). Therefore, it is important that the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of bronchial asthma is maintained.

Switching from systemic corticosteroid therapy to Pulmicort may sometimes result in the emergence of allergic conditions previously controlled by systemic treatment, such as rhinitis and eczema.

Concomitant use with other medicinal products

Concomitant use of this medicinal product with ketoconazole, itraconazole, HIV protease inhibitors, or other potent CYP3A4 inhibitors should be avoided. If this is unavoidable, 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, resulting in reduced drug clearance and development of high systemic exposure. The potential for systemic adverse effects should be considered.

Effect on growth

In children receiving long-term corticosteroid therapy, 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 therapy should be weighed against the potential risk of growth retardation. In addition, referral of the patient to a pediatric pulmonologist may be appropriate.

Oral candidiasis

Oral 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-stage pulmonary 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. Some evidence suggests an increased risk of pneumonia with higher corticosteroid doses, although this has not been definitively demonstrated in any study.

There is a lack of comprehensive clinical evidence regarding intra-class differences in the magnitude of pneumonia risk among inhaled corticosteroid medicinal products.

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

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

Visual disturbances

Visual disturbances may occur during systemic and local use of corticosteroids. If patients experience symptoms such as blurred vision or other visual disturbances, they 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 results from prospective epidemiological studies and worldwide post-marketing data have not identified an increased risk of adverse effects on the fetus or newborn associated with inhaled budesonide use during pregnancy. It is important for both the fetus and the pregnant woman that asthma is adequately controlled during pregnancy. As with other medicinal products used during pregnancy, the benefits of budesonide use for the pregnant woman should be weighed against potential risks to the fetus.

Animal studies have demonstrated 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 influence 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 is excreted in breast milk. However, when therapeutic doses of Pulmicort are used, no effect on the breastfed infant is expected, as systemic exposure to the breastfed infant is negligible. Pulmicort can be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Pulmicort does not affect the ability to drive vehicles or operate machinery.

Method of administration and dosage.

Dosage in bronchial asthma

The dosage of the medicinal product Pulmicort 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 should be:

Children aged 6 months: 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: 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 Pulmicort is preferred over combination therapy with oral corticosteroids, due to the lower risk of systemic adverse effects.

Treatment with the medicinal product Pulmicort allows replacement or substantial reduction of oral corticosteroid dosage while maintaining asthma control. When switching from oral corticosteroids to Pulmicort, the patient should be in a relatively stable condition. For the next 10 days, a high dose of Pulmicort 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 Pulmicort. For additional information regarding withdrawal of oral corticosteroids, see section "Special instructions".

Time to onset of effect in bronchial asthma

After administration of the initial dose, an effect is 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 Pulmicort, suspension for nebulization, divided into two to four 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 admission to intensive care units.

Time to onset of effect in acute exacerbation of COPD

After inhalation of the medicinal product Pulmicort, 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 may be administered as a single dose or as two doses of 1 mg each, administered 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

Hepatic or renal impairment

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

Dosage table

Dose (mg)	Volume of Pulmicort medicinal product, 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

* Dilute to 2 mL with 0.9% sodium chloride solution or nebulizer solution, see "Instructions for use and handling".

Method of administration

Instructions for correct use of the medicinal product Pulmicort, suspension for nebulization

Pulmicort suspension for nebulization is inhaled using a jet nebulizer with a mouthpiece or appropriate breathing mask.

It is important that the patient breathes calmly and evenly through the nebulizer mouthpiece, as budesonide, the active ingredient in Pulmicort suspension for nebulization, reaches the lungs during inhalation.

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

NOTE! It is important to instruct the patient/caregiver to wash the face with water after using a breathing 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 (propeller unit) should be adjusted so that the majority of droplets delivered are within the range of 3–5 µm.

In vitro studies have demonstrated that nebulizers such as Pari Inhalierboy, Pari Master, and Aiolos deliver comparable doses of budesonide.

The amount of budesonide delivered to the patient varies between 11–22% of the dose administered into the nebulizer and depends on the following factors:

• duration of nebulization;
• filling volume;
• technical characteristics of the compressor (propeller unit) and nebulizer;
• patient's tidal volume;
• use of a mouthpiece or breathing mask.

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 can be maximized by using a breathing mask that fits tightly to the face.

Before opening the single-dose container, gently shake it.

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

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

See also the manufacturer's instructions for the nebulizer.

Instructions for use and handling

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

Unused medicinal product or waste material must be disposed of in accordance with national requirements.

Children.

Pulmicort is used in children as indicated (see sections "Indications" and "Dosage and method of administration").

Overdose.

Acute overdose of Pulmicort 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 adrenal suppression.

Adverse reactions.

Frequency is defined as follows: very common (≥1/10); common (from ≥1/100 to <1/10); uncommon (from ≥1/1000 to <1/100); rare (from ≥1/10,000 to <1/1000); very rare (<1/10,000).

Table 1. Adverse drug reactions by organ systems and frequency.

System organ classes	Frequency	Adverse reactions
Infections and infestations	Common	Oropharyngeal candidiasis, pneumonia (in patients with COPD)
Immune system disorders	Uncommon	Immediate and delayed hypersensitivity reactions*, including rash, contact dermatitis, urticaria, angioedema, and anaphylactic reaction
Endocrine system disorders	Uncommon	Signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation**
Eye disorders	Uncommon	Cataract*** Blurred vision (see also section "Special warnings and precautions for use")
	Not known	Glaucoma
Psychiatric disorders	Uncommon	Anxiety, depression
	Uncommon	Nervousness, behavioural changes (mainly in children)
	Not known	Sleep disorders, psychomotor hyperactivity, aggression
Nervous system disorders	Uncommon	Tremor
Respiratory, thoracic and mediastinal disorders	Common	Cough, throat irritation
	Uncommon	Bronchospasm, dysphonia, hoarseness
Skin and subcutaneous tissue disorders	Uncommon	Contusion
Musculoskeletal and connective tissue disorders	Uncommon	Muscle spasms

* 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, which are likely dependent on dose, duration of exposure, concomitant and prior corticosteroid exposure, as well as individual sensitivity.

Immune system disorders

Facial skin irritation has been reported occasionally when a nebulizer with a face mask was used. This is considered a hypersensitivity reaction. To prevent irritation, patients should wash their face with water after each use of the mask.

Infections and infestations

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

Eye disorders

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

Psychiatric disorders

In pooled clinical trial data, 13,119 patients received inhaled budesonide and 7,278 patients 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 suppression in children, growth parameters should be monitored regularly (see section "Special precautions for use").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. 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 the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Use within 3 months after opening the aluminium foil pouches.

If only 1 mL of the suspension has been used, the remaining suspension is no longer sterile and should be immediately discarded.

Storage conditions.

Store at temperatures not exceeding 30 °C. Do not freeze.

Keep out of reach and sight of children.

Store containers in an upright position.

Store containers in the aluminium foil pouch to protect from light.

Incompatibilities.

Pulmicort nebuliser suspension must not be mixed with other medicinal products, except those specified in the "Instructions for use and handling" (see section "Dosage and administration").

Packaging.

2 mL in a plastic container; 5 containers connected together in an aluminium foil pouch; 4 pouches in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

AstraZeneca AB/AstraZeneca AB.

Manufacturer's address.

Forskargatan 18, Södertälje, 151 36, Sweden/Forskargatan 18, Sodertalje, 151 36, Sweden.