Expiration date: 04/2025

The composition and form of issue:

Suspension for inhalation. 1 ml contains active substance:

budesonide 0.25 or 0.5 mg

excipients: disodium edetate sodium chloride Polysorbate 80 citric acid (anhydrous) sodium citrate purified water 

in containers, PE 2 ml 5 containers connected in a single sheet sheet of 5 containers Packed in an envelope made of laminated foil in a cardboard bundle 4 pack.

Description pharmaceutical form:

Easy resuspendiruetsa sterile suspension of white or almost white, in containers of polyethylene of low density containing a single dose.

Pharmacokinetics:

Absorption. Inhalerbuy budesonide is rapidly absorbed. In adults the systemic bioavailability of budesonide after inhalation via Pulmicort suspension nebuliser is approximately 15% of the total assigned dose and about 40-70% of the delivered. Cmax in plasma achieved through 30 minutes after the start of inhalation.

Metabolism and distribution. The plasma protein binding is about 90%. Vd budesonide is approximately 3 l/kg. After absorption budesonide undergoes intense biotransformation (90%) in the liver to form metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6&beta-hydroxy-budesonide and 16&alpha-hydroxyprednisolone is less than 1% of the activity of the glucocorticosteroid budesonide.

Excretion. Budesonide is mainly metabolized with the participation of the enzyme CYP3A4. The metabolites are excreted unchanged with the urine or kongugirovannah form. Budesonide has a high systemic clearance (approximately 1.2 l/min). The pharmacokinetics of budesonide is proportional to the input dose of the drug.

The pharmacokinetics of budesonide in children and patients with impaired renal function have not been investigated. In patients with liver disease may increase the residence time of budesonide in the body.

Description pharmacological action:

Budesonide, inhaled corticosteroids in recommended doses it is anti-inflammatory in the bronchi, reducing the severity of symptoms and frequency of exacerbations of asthma with less adverse effects than when using systemic corticosteroids. Reduces the severity of edema of the bronchial mucosa, production of mucus, the formation of phlegm and Hyper-reactivity of the Airways. Well tolerated in long-term care, has mineralocorticosteroid activity.

The start time for therapeutic effect after inhalation of one dose of the drug is a few hours. The maximum therapeutic effect is achieved within 1-2 weeks after treatment. Budesonide has a prophylactic effect on the course of bronchial asthma and has no effect on the acute manifestations of the disease.

Shown a dose-dependent effect on cortisol in plasma and urine on a background of reception of Pulmicort. In recommended doses, the drug has significantly less effect on adrenal function than prednisone in a dose of 10 mg has been shown in ACTH-tests.

Indications:

• bronchial asthma requiring maintenance therapy of corticosteroids
  
• chronic obstructive pulmonary disease (COPD).
  

Contraindications:

• hypersensitivity to budesonide.
  
• children up to age 6 months.
  

With caution (requires more careful monitoring of patients): patients with active pulmonary tuberculosis and fungal, viral, bacterial respiratory infections, cirrhosis of the liver in the appointment should take into account the possible manifestation of systemic effects of corticosteroids.

Application of pregnancy and breast-feeding:

Pregnancy. Surveillance of pregnant women taking budesonide, showed no abnormalities in the fetus, however, cannot completely eliminate the risk of their development, therefore, during pregnancy, in connection with the possibility of worsening of bronchial asthma, you should use the minimum effective dose of budesonide.

Lactation. Budesonide passes into breast milk, however, the application of Pulmicort in therapeutic doses, effects on the child are not marked. Pulmicort can be used during breast-feeding.

Side effects:

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

Frequent (>1/100)

From the respiratory tract, candidiasis of the oropharynx, irritation of the mucous membrane of the throat, cough, hoarseness, dry mouth.

Rare (<1/1000)

General: angioedema.

The skin: urticaria, rash, contact dermatitis.

From the respiratory: bronchospasm.

There may be some neuropsychiatric symptoms such as nervousness, anxiety, depression, behavior disorders. Taking into account the risk of candidiasis of the oropharynx, the patient should thoroughly rinse your mouth with water after each inhalation drug.

In rare cases there can be symptoms caused by a systemic effect of corticosteroids, including adrenal hypofunction.

In rare cases, observed the bruising on the skin.

There have been cases of irritation of the skin when using a nebulizer with a mask. To prevent irritation after using the mask the face should be washed with water.

Drug interactions:

There was no interaction of budesonide with other drugs used in the treatment of bronchial asthma.

Ketoconazole (the dose of 200 mg 1 time per day) increases plasma concentration of oral budesonide (at a dose of 3 mg 1 time per day) on average, 6-fold when co-administered. When taking ketoconazole within 12 h after administration of budesonide, the concentration of the latter in blood plasma increased on average by 3 times. Information about such interactions when taking budesonide in the inhalation form is missing, however, it is assumed that in this case we should expect increasing the concentration of budesonide in plasma. In case of necessity of reception of ketoconazole and budesonide should increase the time between the administration of drugs to the maximum possible. You should also consider the possibility of reducing the dose of budesonide. Another potential inhibitor of CYP3A4 (e.g., Itraconazole) significantly increases plasma concentration of budesonide.

Preliminary inhalation of beta-agonists dilates the bronchi, improve the flow of budesonide in the Airways and enhances its therapeutic effect.

Phenobarbital, phenytoin, rifampicin reduces the efficacy (induction of enzymes of microsomal oxidation) of budesonide.

Methandrostenolone, estrogens increase the effect of budesonide.

Method of application and dose:

Inhalation. Dose selected individually. If the recommended dose does not exceed 1 mg/day, the entire dose can be taken 1 time (once). In case a higher dose is recommended divided into 2 doses.

Recommended starting dose:

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

Adults/elderly patients 1-2 mg/day.

Dose for maintenance treatment:

Children from 6 months and over is 0.25–2 mg/day.

Adults — 0,5–4 mg/day. In the case of severe exacerbations, the dose may be increased.

Table for determining the dose

Dose, mg	The amount of the drug Pulmicort, suspension for inhalation
	0.25 mg/ml budesonide	0.5 mg/ml budesonide
0,25	1 ml*	-
0,5	2 ml	-
0,75	3 ml	-
1	4 ml	2 ml
1,5	-	3 ml
2	-	4 ml

* Should be diluted with 0.9% saline to a volume of 2 ml

For all patients it is desirable to determine the minimum effective maintenance dose.

If necessary to achieve additional therapeutic effect, we recommend increasing the daily dose of Pulmicort is the combination of the drug with oral corticosteroids, due to the lower risk of systemic effects.

Patients receiving oral corticosteroids

Discontinuation of oral GCS should start on the background of a stable state of health of the patient. Within 10 days it is necessary to take a high dose of Pulmicort in patients receiving oral corticosteroids at the usual dosage. In the next 1 month should gradually reduce the dose of oral steroids (for example 2.5 mg prednisolone or equivalent) to the minimum effective dose. In many cases it is possible to completely abandon the use of oral glucocorticoids.

Since the Pulmicort to be applied in suspension with a nebulizer, into the lungs when you inhale, it is important to instruct the patient to inhale the drug through the mouthpiece of the nebulizer safely and smoothly.

No data on the use of budesonide in patients with renal insufficiency or impaired liver function. Taking into account the fact that budesonide is eliminated by biotransformation in the liver, one can expect an increase in the duration of action of the drug in patients with severe liver cirrhosis.

Overdose:

Symptoms: in acute overdose, clinical manifestations does not occur. Prolonged use of the drug in doses, greatly exceeding recommended, may develop systemic glucocorticosteroid effect of hypercortisolism and suppression of adrenal function.

Special instructions:

To minimize the risk of fungal infection of the oropharynx should inform the patient about the need to rinse your mouth thoroughly with water after each inhalation drug.

Avoid joint appointment budesonide with ketoconazole, Itraconazole or other potential CYP3A4 inhibitors. In the case of budesonide and ketoconazole or other potential CYP3A4 inhibitors was appointed, increase the time between administration of drugs to the maximum possible.

Because of the potential risk of weakening of the adrenal function, special attention should be paid to patients who are transferred from oral corticosteroids to receive Pulmicort. Also, special attention should be given to patients taking high-dose corticosteroids, or long-term receiving the highest recommended dose of inhaled corticosteroids. In stressful situations, such patients may manifest the signs and symptoms of adrenal insufficiency. Under stress or in cases of surgical intervention is recommended for more therapy systemic corticosteroids.

Special attention should be given to patients who are transferred from systemic to inhaled corticosteroids (Pulmicort), or in the case, when can we expect impairment of the pituitary-adrenal function. In such patients, should take special precautions to reduce the dose of systemic corticosteroids and control of the hypothalamic-pituitary-adrenal function. Also patients may need the addition of oral corticosteroids during stressful situations such as trauma, surgery, etc.

When switching from oral corticosteroids to Pulmicort, patients may feel the previously observed symptoms such as muscle pain or joint pain. In such cases, you may need a temporary increase in the dose of oral corticosteroids. In rare cases, there may be symptoms such as fatigue, headache, nausea and vomiting, indicating a systemic failure of GKS.

Replacement of oral corticosteroids to inhaled sometimes leads to the manifestation of concomitant allergies (e.g., rhinitis and eczema) which were previously stoped systemic drugs.

In children and adolescents receiving treatment with glucocorticoids (regardless of method of delivery) over an extended period, it is recommended to regularly monitor the growth. When assigning GCS should take into account the ratio of use of the drug and the possible risk of slower growth.

The use of budesonide at a dose of 400 mg/day in children older than 3 years have not resulted in systemic effects. Biochemical signs of systemic effect of the drug can occur with the drug in a dose of 400 to 800 mg/day. When the dose of 800 mg/day systemic effects of the drug are common.

The use of corticosteroids for treatment of asthma can cause impaired growth. The results of observation of children and adolescents treated with budesonide for a long period (up to 11 years) showed that the growth of patients reaching the expected standard indicators for adults.

Therapy inhaled budesonide 1 or 2 times a day has shown efficacy for prevention of asthma physical effort.

Effects on ability to drive or other mechanisms. Pulmicort does not affect the ability to drive or other mechanisms.

The use of Pulmicort via nebulizer

Pulmicort is used for inhalation using an appropriate nebulizer, equipped with a mouthpiece and a special mask. The nebulizer connects to the compressor to create the required air flow (5-8 l/min), filling volume of the nebulizer should be 2-4 ml.

It is important to inform the patient:

• carefully read the instructions for use of the drug
  
• for use of Pulmicort suspension are not suitable for ultrasonic nebulizers
  
• Pulmicort suspension is mixed with 0.9% sodium chloride solution or with solutions of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate and ipratropium bromide diluted suspension should be used within 30 min.
  
• after inhalation should rinse your mouth with water to reduce the development of candidiasis of the oropharynx
  
• to prevent skin irritation after using the mask, rinse your face with water
  
• it is recommended to regularly clean the nebulizer in accordance with the manufacturer's instructions.
  
• In cases where the child cannot breathe through the nebulizer, uses a special mask.
  

How to use Pulmicort with a nebulizer

1. Before use, gently shake the container a slight twisting motion.

2. Keep container straight vertically and open it, turning and taking his "wing".

3. Carefully place the open end of the container in the nebulizer and slowly squeeze the contents of the container.

A container containing a single dose, marked line. If the container is inverted, this line will show the volume equal to 1 ml.

If you want to use only 1 ml of the suspension, the contents of the container squeezed until then, until the liquid surface reaches the level indicated by the line.

Open container stored in a dark place. Open container must be used within 12 h

Before you can use the leftover liquid contents of the container gently shaken with a rotary motion.

Note

1. After each inhalation should rinse your mouth with water.

2. If the patient uses a mask, you must ensure that inhalation of the mask tightly to the face. Wash your face after inhalation.

Cleaning

Chamber of the nebulizer, mouthpiece or mask should be cleaned after each use.

Chamber of the nebulizer, mouthpiece or mask, wash with warm water using a mild detergent or according to the manufacturer's instructions. A good rinse and dry nebulizer, connecting the camera with the compressor or air inlet valve.

Expiration date:

3 months after opening of the envelope 12 h after opening of the container.