Pulmicort, 0.25 mg/ml 2 ml 20 pcs.

Pharmacotherapeutic group Glucocorticosteroid for topical use. ATX code: R03BA02

Pharmacological Properties

Pharmacodynamics

Budesonide, an inhaled glucocorticosteroid, at recommended doses has an anti-inflammatory effect in the bronchi, reducing the severity of symptoms and the frequency of exacerbations of bronchial asthma with a lower frequency of side effects than with systemic glucocorticosteroids. It reduces the severity of bronchial mucosal edema, mucus production, sputum formation and airway hyperresponsiveness. It is well tolerated with long-term treatment, has no mineralocorticosteroid activity.

Dose-dependent effects on plasma and urinary cortisol levels during administration of Pulmicort^® have been shown. At the recommended doses, the drug has significantly less effect on adrenal function than prednisolone at a dose of 10 mg, as shown in ACTH tests.

In bronchial asthma and the use of inhaled glucocorticosteroids, growth retardation may be noted. Studies with children and adolescents who received therapy with budesonide for a long time (up to 13 years) have shown that patients achieved the expected growth in adulthood.

Inhaled budesonide therapy is effective in preventing bronchial asthma of physical effort.

Clinical studies with exacerbations of chronic obstructive pulmonary disease (COPD.Several studies of nebulized budesonide at a dose of 4-8 mg/day have shown efficacy in the therapy of exacerbations of COPD.

Clinical Studies – Bronchial Asthma

The efficacy of Pulmicort^® has been evaluated in numerous studies. The drug has been shown to be effective in the treatment of persistent bronchial asthma in both adults and children when used once or twice daily. Inhaled budesonide has also been shown to be effective in the therapy and prevention of exacerbations of bronchial asthma in children and adults.

Population of pediatric patients Clinical studies – false croup

A number of studies in children with false croup have compared Pulmicort^® with placebo. Below are examples of representative studies evaluating the use of Pulmicort^® for the treatment of children with false croup.

Effectiveness in children with mild to moderate false croup

A randomized, double-blind, placebo-controlled trial involving 87 children aged 7 months to 9 years hospitalized with a clinical diagnosis of false croup was conducted to determine whether Pulmicort improves the efficacy of Pulmicort^®, a suspension, improved the assessment of false croup symptoms or shortened the duration of hospital treatment. Patients received Pulmicort^®, suspension, at an initial dose of 2 mg or placebo, followed by Pulmicort^® at a dose of 1 mg or placebo every 12 hours.

Pulmicort^®, suspension, resulted in statistically significant reductions in the severity of false croup symptoms after 12 hours and 24 hours and 2 hours after administration in a subgroup of patients with a baseline symptom score above 3. The duration of inpatient treatment was also reduced by 33%.

Effectiveness in children with moderate to severe false croup

A randomized, double-blind, placebo-controlled trial compared the effectiveness of Pulmicort^® and placebo in the treatment of false croup in 83 infants and children (ages 6 months to 8 years) hospitalized for false croup. Patients received Pulmicort^®, suspension, 2 mg or placebo every 12 hours for up to 36 hours or until hospital discharge. An overall assessment of false croup symptoms was performed at 0, 2, 6, 12, 24, 36, and 48 hours after the initial dose was administered. After 2 hours, both the Pulmicort^® and placebo groups showed a similar reduction in the severity of false croup symptoms, with no statistically significant difference between the groups. Six hours after the initial dose, there was a statistically significant reduction in the severity of false croup symptoms in the Pulmicort^®, suspension group compared to the placebo group, and this improvement was similar after 12 hours and 24 hours.

Pharmacokinetics

.Absorption

Inhaled budesonide is rapidly absorbed. In adults, the systemic bioavailability of budesonide after inhalation of Pulmicort^® via nebulizer is approximately 15% of the total dose administered and approximately 40-70% of the dose delivered.

The maximum plasma concentration is reached 30 minutes after initiation of inhalation.

Metabolism and distribution

The binding to plasma proteins averages 90%. The volume of distribution of budesonide is approximately 3 L/kg. After absorption budesonide undergoes intensive (over 90%) biotransformation in the liver to form metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites 6b-hydroxybudesonide and 16a-hydroxyprednisolone is less than 1% of the glucocorticosteroid activity of budesonide.

Elimation

Budesonide is metabolized mainly with participation of CYP3A4 enzyme. Metabolites are excreted unchanged in the urine or in conjugated form. Budesonide has high systemic clearance (about 1.2 l/min). Pharmacokinetics of budesonide is proportional to the administered dose of the drug.

The pharmacokinetics of budesonide in patients with impaired renal function has not been studied. Exposure to budesonide may be increased in patients with liver disease.

Indications

Active ingredient

Composition

1 ml of the suspension contains:

The active ingredient: budesonide (budesonide micronized) 0.25 mg or 0.5 mg.

Auxiliary ingredients: sodium chloride 8.5 mg, sodium citrate 0.5 mg, edetate disodium (sodium salt of ethylenediaminetetraacetic acid (divalent) (EDTA disodium salt)) 0.1 mg, polysorbate 80 0.2 mg, citric acid (anhydrous) 0.28 mg, purified water up to 1 ml.

How to take, the dosage

The dose of the drug is adjusted individually. If the recommended dose does not exceed 1 mg/day, the entire dose of the drug may be taken at once (one time). If a higher dose is taken, it is recommended that it be divided into two doses. It is desirable to determine a minimum effective maintenance dose for all patients.

Precommended starting dose:

Children 6 months and older: 0.25-0.5 mg per day. If necessary, the dose can be increased to 1 mg/day.

Adults/elderly patients: 1-2 mg per day.

Dose in maintenance treatment:

Children 6 months and older: 0.25-2 mg daily.

Adults/elderly patients: 0.5-4 mg daily.

In case of severe exacerbations, the dose may be increased.

If additional therapeutic benefit is needed, increasing the daily dose of Pulmicort® instead of combining the drug with oral glucocorticosteroids may be recommended because of the lower risk of systemic effects.

Effects with maintenance treatment

Bronchial asthma control improved with maintenance therapy with Pulmicort

sup>® may occur within 3 days of starting treatment, although the maximum effect may not be achieved in 2 to 4 weeks.

Patients receiving oral glucocorticosteroids

The withdrawal of oral glucocorticosteroids should be initiated with the patient stable. Within 10 days the high dose of Pulmicort® should be taken against the background of therapy with oral glucocorticosteroids in usual dose. Thereafter, the dose of oral glucocorticosteroids (e.g., 2.5 mg of prednisolone or its analogues) should be gradually reduced over a month to the lowest effective dose. In many cases, it is possible to stop taking oral glucocorticosteroids completely.

Supportive therapy for COPD

The dose of the drug is chosen individually. If the recommended dose is less than 1 mg/day, the entire dose can be taken at once (one time). If a higher dose is taken, it is recommended that it be divided into two doses. It is desirable to determine a minimum effective maintenance dose for all patients.

Recommended starting dose:

Adults/Elderly patients: 1-2 mg per day.

Dose in maintenance treatment:

Adult/older patients: 0.5-4 mg per day.

Adults/Elderly Patients

The daily dose is 4-8 mg. The dose should be divided into 2-4 doses. Treatment should be continued until clinical improvement is achieved, but no more than 10 days.

Effect Generation

After inhalation of Pulmicort® for treatment of exacerbations of COPD, the time to improvement of symptoms is comparable to that with systemic corticosteroids.

Children 6 months and older: 2 mg daily. The dose of the drug can be taken at a time (one time) or divided into two doses of 1 mg at 30-minute intervals.

Hepatic or renal impairment

There are no data on the use of budesonide in patients with hepatic or renal impairment. Given that budesonide is excreted by biotransformation in the liver, increased drug exposure can be expected in patients with severe hepatic cirrhosis.

Dose, mg

Dose

Pulmicort® inhalation suspension

0.25 mg/mL

0.5 mg/mL

0.25

1 ml*

–

Interaction

Special Instructions

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

In case of an exacerbation, the dose of Pulmicort® may be increased or short-term adjunctive therapy may be prescribed.

As with other inhalation therapy, paradoxical bronchospasm may occur with immediate increased wheezing after administration of Pulmicort®. In this case, therapy with inhaled budesonide should be stopped immediately, the patient’s condition should be evaluated, and if necessary, alternative therapy should be prescribed.

Fungal oral infections may occur with the use of inhaled glucocorticosteroids. If this infection develops, appropriate antifungal medications may be required, and in some patients, withdrawal of the inhaled glucocorticosteroids may be necessary. To reduce the risk of oropharyngeal fungal infection, patients should be instructed to rinse their mouth thoroughly with water after each inhalation of the drug.

The co-administration of budesonide with ketoconazole, itraconazole, or other potent CYP3A4 inhibitors should be avoided. If budesonide and ketoconazole or other potent CYP3A4 inhibitors have been prescribed, the time between doses should be increased to the maximum possible.

Because of the possible risk of impaired adrenal function, special consideration should be given to patients being switched from oral glucocorticosteroids to taking Pulmicort ®. Special attention should also be paid to patients who have taken high doses of glucocorticosteroids, or who have received the highest recommended dose of inhaled glucocorticosteroids for a long time. Such patients may show signs and symptoms of adrenal insufficiency in stressful situations. Additional therapy with systemic glucocorticosteroids is recommended for stressful situations or in cases of surgical intervention.

Particular attention should be given to patients being switched from systemic to inhaled glucocorticosteroids (Pulmicort®) or in cases where pituitary-adrenal dysfunction can be expected. In such patients, the dose of systemic glucocorticosteroids should be reduced with special caution and hypothalamic-pituitary-adrenal function should be monitored. Patients may also need to be supplemented with oral glucocorticosteroids during stressful situations such as trauma, surgery, etc.

When switching from oral glucocorticosteroids to Pulmicort ®, patients may experience previously observed symptoms such as muscle pain or joint pain. In such cases, a temporary increase in the dose of oral glucocorticosteroids may be needed. In rare cases, symptoms such as fatigue, headache, nausea, and vomiting may occur, indicating systemic glucocorticosteroid insufficiency.

Changing oral glucocorticosteroids to inhaled glucocorticosteroids sometimes results in associated allergies, such as rhinitis and eczema, that were previously controlled with systemic medications.

In children and adolescents treated with glucocorticosteroids (regardless of mode of delivery) over a prolonged period, it is recommended that growth rates be monitored regularly. If growth retardation occurs, therapy should be revised to reduce the dose of inhaled glucocorticosteroid, if possible, to the lowest dose at which effective control of bronchial asthma can be maintained. The balance between the benefits of glucocorticosteroid therapy and the possible risk of growth retardation should be carefully evaluated. In addition, it is recommended that the patient be referred to a pediatric pulmonologist.

The use of budesonide at doses up to 400 mcg per day in children over 3 years of age has not resulted in systemic effects. Biochemical signs of systemic effects of the drug may occur when taking the drug in a dose of 400 to 800 mcg per day. When the dose of 800 mcg per day is exceeded, systemic effects of the drug are common.

Systemic effects can occur with any inhaled glucocorticosteroid, especially when used in high doses over a long period of time. The likelihood of developing these symptoms is significantly less with inhaled glucocorticosteroid therapy than with oral glucocorticosteroids.

Possible systemic effects include Cushing’s syndrome, cushingoid traits, suppression of adrenal function, growth retardation in children and adolescents, reduced bone mineral density, cataracts, glaucoma, psychological symptoms and behavior disorders including psychomotor hyperactivity, sleep disorders, anxiety, depression and aggression, especially in children (see side effects section). The dose of inhaled glucocorticosteroid should be the lowest dose at which effective disease control is maintained.

Hepatic impairment may affect glucocorticosteroid excretion, causing decreased excretion rates and increased systemic exposure. Patients should be warned about possible systemic adverse reactions.

Clinical studies and meta-analyses have shown that the use of inhaled glucocorticosteroids in maintenance therapy for COPD can lead to an increased risk of pneumonia. Physicians should be aware of the possibility of pneumonia in patients with COPD, because clinical signs of pneumonia and exacerbations often coincide.

Perhaps visual disturbances can occur with systemic and topical use of glucocorticosteroids. If a patient presents with symptoms such as blurred vision or other visual disturbances, consideration should be given to referring the patient to an ophthalmologist to assess possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous retinopathy (CSR) noted after systemic and topical glucocorticosteroid use.

Synopsis

Contraindications

Side effects

The incidence of adverse effects is as follows:

Frequent (> 1/100, < 1/10); Infrequent (> 1/1000, < 1/100); Rare (> 1/10000, < 1/1000); Very rare (< 1/10000), including individual reports.

Up to 10% of patients taking the drug may experience the following side effects:

Often

Respiratory:

Oropharyngeal candidiasis, moderate irritation of throat mucosa, cough, hoarseness of voice, dry mouth, pneumonia (in patients

with COPD).

Rarely

General:

Skin:

Respiratory: Central nervous system:

The immune system:

The gastrointestinal tract:

Angioedema.

The appearance of bruising of the skin.

Bronchospasm. Nervousness, excitability,

depression, behavioral disorders.

Hypersensitivity reactions of immediate and delayed type, including rash, contact dermatitis, urticaria, angioedema, bronchospasm, and anaphylactic reaction.

Nausea.

Very rare

Laboratory findings:

Sense organs:

Decrease in bone mineral density (systemic effect).

Cataracts, glaucoma

(systemic effect).

With the risk of oropharyngeal candidiasis, patients should rinse their mouth thoroughly with water after each inhalation of the drug.

In rare cases, symptoms due to systemic effects of glucocorticosteroids may occur, including adrenal hypofunction and growth retardation in children. The severity of these symptoms probably depends on the drug dose, duration of therapy, concomitant or previous glucocorticosteroid therapy, and individual sensitivity.

There have been cases of facial skin irritation when using a nebulizer with a mask. To prevent irritation, you should wash your face with water after using the mask.

Overdose

Pregnancy use

Similarities