Pulmikort

General characteristics. Structure:

Contains in 1 ml of suspension:
Active ingredient: будесонид (будесонид micronized) 0,25 mg or 0,5 mg.
Auxiliary ingredients: sodium chloride of 8,5 mg, sodium citrate of 0,5 mg, эдетат dinatrium (sodium salt of ethylene diamine tetraacetic acid (two-replaced) (EDTA disodium salt)) 0,1 mg, polysorbate of 80 0,2 mg, the citric acid (anhydrous) 0,28 mg, water purified to 1 ml.
Description
Easily resuspended sterile suspension of white or almost white color in the containers from polyethylene of low density containing a single dose.

Pharmacological properties:

Pharmacodynamics. Budesonid, an inhalation glucocorticosteroid, in the recommended doses has antiinflammatory effect in bronchial tubes, reducing expressiveness of symptoms and frequency of exacerbations of bronchial asthma with a smaller frequency of side effects, than when using system glucocorticosteroids. Reduces expressiveness of hypostasis mucous bronchial tubes, products of slime, formation of a phlegm and hyperreactivity of respiratory tracts. It is well transferred at prolonged treatment, has no mineralokortikosteroidny activity.
Time of the beginning of therapeutic effect after inhalation of one dose of drug makes several hours. The maximum therapeutic effect is reached in 1 - 2 weeks after treatment. Budesonid has preventive effect on the course of bronchial asthma and does not influence acute manifestations
diseases.
Dozozavisimy impact on the maintenance of cortisol in plasma and urine against the background of Pulmikort's reception is shown. In the recommended doses drug exerts considerably smaller impact on epinephral function, than Prednisonum in a dose of 10 mg as it was shown in AKTG tests.

Pharmacokinetics. Absorption Inhalated будесонид quickly is absorbed. Adults have a system bioavailability of a budesonid after Pulmikort's inhalation of suspension via the nebulizer, makes about 15% of the general appointed dose and about 40-70% of delivered. The maximum concentration in a blood plasma is reached in 30 minutes after the beginning of inhalation. Metabolism and distribution Communication with proteins of plasma averages 90%. The volume of distribution of a budesonid makes about 3 l/kg. After absorption будесонид is exposed to intensive biotransformation (more than 90%) in a liver with formation of metabolites with low glucocorticosteroid activity. Glucocorticosteroid activity of the main metabolites 6β-hydroxy-budesonida and 16α-hydroxyprednisolonum makes less than 1% of glucocorticosteroid activity of a budesonid.
Removal Budesonid is metabolized generally with CYP3A4 enzyme participation. Metabolites are removed in not changed view with urine or in the conjugated form. Budesonid has high system clearance (about 1,2 l/min). The pharmacokinetics of a budesonid is proportional to the size of the entered drug dose.
The pharmacokinetics of a budesonid at children and patients with a renal failure was not investigated. At patients with diseases of a liver the time spent of a budesonid in an organism can increase.

Indications to use:

• The bronchial asthma demanding a maintenance therapy
glucocorticosteroids
• Chronic Obstructive Pulmonary Disease (COPD)
• The stenosing laryngotracheitis (false croup).

Route of administration and doses:

The dose of drug is selected individually. If the recommended dose does not exceed 1 mg/days, all dose of drug can be accepted for once (once). In case of reception of higher dose it is recommended to divide it into two receptions.
Children of 6 months are also more senior: 0,25 - 0,5 mg a day. If necessary the dose can be increased to 1 mg/days.
The recommended initial dose:
Adult/elderly patients: 1 - 2 mg a day.
Children of 6 months are also more senior: 0,25 - 2 mg a day.
Dose at the supporting treatment:
Adults: 0,5 - 4 mg a day. In case of heavy aggravations the dose can be increased.
The table for definition of a dose

Dose, mg                                       drug Volume
                                    Pulmikort suspension for inhalations    
                                     0,25                     mg/ml 0,5 mg/ml
0,25                              1 ml *                                -
0,5                                2 ml                                  -
0,75                              3 ml                                  -
1                                   4                               ml 2 ml
                                1,5 -                                     3 ml
                                   2 -                                     4 ml

*) it is necessary to dilute 0,9% with chloride sodium solution up to the volume of 2 ml
For all patients it is desirable to define the minimum effective maintenance dose.
In case of need achievements of additional therapeutic effect
it is possible to recommend increase in a daily dose (to 1 mg/days) Pulmikorta instead of a drug combination with peroral glucocorticosteroids, thanks to lower risk of development of system effects.
The patients receiving peroral glucocorticosteroids
Cancellation of peroral glucocorticosteroids needs to be begun against the background of the stable state of health of the patient. Within 10 days it is necessary to accept a high dose of Pulmikort against the background of reception of peroral glucocorticosteroids in a usual dose. Further within a month it is necessary to reduce gradually a dose of peroral glucocorticosteroids (for example, on 2,5 mg of Prednisolonum or its analog) to a minimal effective dose. In many cases it is possible to refuse reception of peroral glucocorticosteroids completely.
As Pulmikort applied in the form of suspension by means of the nebulizer gets into lungs at a breath important to instruct the patient to inhale drug through a nebulizer mouthpiece quietly and exactly.
There are no data on use of a budesonid for patients with a renal failure or an abnormal liver function. In view of the fact that будесонид it is removed by biotransformation in a liver it is possible to expect increase in duration of effect of drug at patients with the expressed cirrhosis.
The stenosing laryngotracheitis (false croup):
Children of 6 months are also more senior: 2 mg a day. The dose of drug can be accepted for once (once) or to divide it into two receptions on 1 mg at an interval of 30 min.

Features of use:

For minimizing of risk of a fungal infection of a stomatopharynx it is necessary to instruct the patient about need to carefully rinse a mouth water after each inhalation of drug.
It is necessary to avoid joint purpose of a budesonid with ketokonazoly, itrakonazoly or other potential CYP3A4 inhibitors. If будесонид and кетоконазол or other potential CYP3A4 inhibitors were appointed, it is necessary to increase time between administration of drugs to greatest possible.
Because of possible risk of weakening of function of adrenal glands special attention needs to be paid to patients who are transferred from peroral glucocorticosteroids on Pulmikort's reception. Also special attention should be paid to the patients accepting high doses of glucocorticosteroids or it is long receiving the highest recommended doses of inhalation glucocorticosteroids. In stressful situations at such patients signs and symptoms of adrenal insufficiency can be shown. At stresses or in cases of surgical intervention it is recommended to carry out additional therapy by system glucocorticosteroids.
Special attention needs to be paid to patients who are transferred with system to inhalation glucocorticosteroids (Pulmikort) or in case it is possible to expect disturbance of pituitary and adrenal function. At such patients it is necessary to reduce a dose of system glucocorticosteroids with extra care and to control гипоталамо - pituitary and adrenal function. Also addition of peroral glucocorticosteroids in the period of stressful situations, such as an injury, surgical intervention, etc. can be required by patients.
Upon transition from peroral glucocorticosteroids on Pulmikort patients can feel earlier observed symptoms, such as muscular pains or joint pains. In such cases temporary increase in a dose of peroral glucocorticosteroids can be necessary. In rare instances such symptoms as the feeling of fatigue, a headache, nausea and vomitings indicating system insufficiency of glucocorticosteroids can be observed.
Replacement of peroral glucocorticosteroids on inhalation sometimes leads to display of the accompanying allergy, for example, of rhinitis and eczema which were stopped by system drugs earlier.
At the children and teenagers receiving treatment by glucocorticosteroids (irrespective of a way of delivery) during the long period, it is recommended to control growth indicators regularly. At purpose of glucocorticosteroids it is necessary to take a ratio of advantage of use of drug and possible risk of delay of growth into account.
Use of a budesonid in a dose to 400 mkg a day at children is more senior than 3 years did not lead to emergence of system effects. Biochemical signs of system effect of drug can meet at administration of drug in a dose from 400 to 800 mkg a day. At exceeding of a dose of 800 mkg a day system effects of drug meet often.
Use of glucocorticosteroids for treatment of bronchial asthma can cause a growth disorder. Results of observations of the children and teenagers receiving будесонид during the long period (up to 11 years), showed that growth of patients reaches the expected normative indicators for adults.
Therapy by an inhalation budesonid 1 or 2 times a day showed efficiency for prevention of bronchial asthma of physical effort.
INFLUENCE ON ABILITY TO DRIVE THE CAR OR OTHER MECHANISMS
Pulmikort does not exert impact on ability to drive the car or other mechanisms.
Pulmikort's use by means of the nebulizer
Pulmikort is applied to inhalations with use of the corresponding nebulizer equipped with a mouthpiece and a special mask. The nebulizer connects to the compressor for creation of a necessary air flow (5 - 8 l/min), the volume of filling of the nebulizer has to make 2 - 4 ml.
It is important to inform the patient:
- to attentively read the instruction for drug use;
- suspensions are not suitable for Pulmikort's use ultrasonic nebulizers;
- Pulmikort suspension is mixed from 0,9% solution of sodium of chloride or with solutions of a terbutalin, salbutamol, Fenoterolum, Acetylcysteinum, sodium of a kromoglikat and ipratropium of bromide; the diluted suspension should be used within 30 min.
- after inhalation it is necessary to rinse a mouth water for decrease in development of candidiasis of a stomatopharynx;
- for prevention of irritation of skin after use of a mask it is necessary to wash out face skin water;
- it is regularly recommended to carry out cleaning of the nebulizer according to instructions of the manufacturer;
In cases when the child cannot independently make a breath via the nebulizer, the special mask is applied.
How to use Пульмикорт by means of the nebulizer
1. Before use carefully stir up a container easy rotary motion.
2. You hold a container directly vertically (as shown in the drawing) and open it, turning and tearing off "wing".
3. Accurately place a container the open end in the nebulizer and slowly squeeze out container contents.
The container containing a single dose is marked by the line. If to turn a container, then this line will show the volume equal to 1 ml.
If it is necessary to use only 1 ml of suspension, contents of a container are squeezed out until the surface of liquid does not reach the level designated by the line.
The open container is stored in the place protected from light. The open container has to be used within 12 hours.
Before using the liquid rest, container contents are carefully stirred up rotary motion.
Note
1. After each inhalation rinse a mouth water.
2. If you use a mask, be convinced that at inhalation the mask densely adjoins to the person. Wash up a face after inhalation.
Cleaning
The nebulizer camera, mouthpiece or mask should be cleared after each use.
The nebulizer camera, mouthpiece or mask are washed with warm water, using soft detergent or according to instructions of the producer. Well rinse and dry up the nebulizer, having connected the camera to the compressor or the entrance air valve.

Side effects:

Frequency of emergence of undesirable effects is presented as follows:
Often (> 1/100, <1/10); Infrequently (> 1/1000, <1/100); Seldom (> 1/10000, <1/1000); Very seldom (<1/10000), including separate messages.
To 10% of the patients accepting drug can test the following side effects:
Often
Respiratory tracts:
Stomatopharynx candidiasis, moderate irritation of a mucous membrane of a throat, cough, hoarseness of a voice, dryness in a mouth.
Often
Respiratory tracts:
Stomatopharynx candidiasis, moderate irritation of a mucous membrane of a throat, cough, hoarseness of a voice, dryness in a mouth.
Seldom
The general: Quincke's disease.
Skin: Emergence of bruises on skin.
Respiratory tracts: Bronchospasm.
Central nervous system: Nervousness, excitability, depression, behavior disorders.
Immune system: Reactions of hypersensitivity of the immediate and slowed-down type, including rash, contact dermatitis, a small tortoiseshell, a Quincke's disease, a bronchospasm and anaphylactic reaction.
Digestive tract: Nausea.
Very seldom
Laboratory indicators: Reduction of mineral density of a bone tissue (systemic action).
Sense bodys: Cataract, glaucoma (systemic action).
In view of risk of development of candidiasis of a stomatopharynx, the patient has to rinse carefully a mouth water after each inhalation of drug.
In rare instances there can be symptoms caused by systemic action of glucocorticosteroids including a hypoadrenalism and delay of growth at children. Expressiveness of these symptoms probably depends on a dose of drug, duration of the therapy accompanying or the previous therapy by glucocorticosteroids, and also individual sensitivity.
Cases of irritation of face skin when using the nebulizer with a mask were noted. For the prevention of irritation after use of a mask the face should be washed up water.

Interaction with other medicines:

Interaction of a budesonid with other drugs used at treatment of bronchial asthma was not observed.
Ketokonazol (200 mg once a day) increases plasma concentration of a peroral budesonid (3 mg once a day) on average by 6 times at joint reception. At reception of a ketokonazol in 12 hours after reception of a budesonid concentration of the last in a blood plasma increased on average by 3 times. Information on similar interaction at reception of a budesonid in the form of inhalation is absent, however it is supposed, as in this case it is necessary to expect increase in concentration of a budesonid in a blood plasma. In case of need reception of a ketokonazol and a budesonid it is necessary to increase time between administration of drugs to greatest possible. Also it is necessary to consider the possibility of a dose decline of a budesonid. Other potential CYP3A4 inhibitor, for example, итраконазол, also considerably increases plasma concentration of a budesonid.
Preliminary inhalation beta адреностимуляторов expands bronchial tubes, improves receipt of a budesonid in respiratory tracts and strengthens its therapeutic effect.
Phenobarbital, Phenytoinum, rifampicin reduce efficiency (induction of enzymes of a microsomal oxidation) of a budesonid.
Methandrostenolone, estrogen strengthen action of a budesonid.

Contraindications:

• Hypersensitivity to a budesonid
• Children's age up to 6 months

With care (more careful observation of patients is required): at
patients with fungal, viral, bacterial infections of bodies
breath, cirrhosis; at appointment it is necessary to take possible manifestation of systemic action of glucocorticosteroids into account.

USE DURING PREGNANCY AND THE LACTATION
Pregnancy: observation of the pregnant women accepting будесонид did not reveal anomalies of development in a fruit, nevertheless it is impossible to exclude completely risk of their development therefore during pregnancy in connection with a possibility of deterioration in a course of bronchial asthma it is necessary to use a minimal effective dose of a budesonid.
Lactation: Budesonid gets into breast milk, however at Pulmikort's use in therapeutic doses of impact on the child it is noted. Pulmikort can be applied during chest feeding.

Overdose:

At acute overdose of clinical manifestations does not arise. At long use of drug in the doses considerably exceeding recommended the system glucocorticosteroid effect in the form of a hypercorticoidism and suppression of function of adrenal glands can develop.

Storage conditions:

At a temperature below 30 °C. To store in the place, unavailable to children. Drug in containers has to be used within 3 months after opening of an envelope. The open container has to be used within 12 hours. Containers should be stored in an envelope for protection them from light. Period of validity 2 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Suspension for inhalations dosed 0,25 mg/ml and 0,5 mg/ml. On 2 ml of drug in a container from polyethylene of low density. 5 containers are connected in one leaf. The leaf from 5 containers is packed into an envelope from the laminated foil. 4 envelopes in a cardboard pack with the application instruction.