Budenit Steri-Neb (Budesonide) suspension for ingalation 0.25mg/ml 2ml 20 vials, 0.5mg/ml 2ml 20 vials, 0.5mg/ml 2ml 60 vials,

0.5mg/ml 2ml 20 vials – 01/2019 

0.25mg/ml 2ml 60 vials – 12/2018 

0.5mg/ml 2ml 20 vials – 11/2018 

The composition and form of issue:

Suspension for inhalation. 1 ml contains:

budesonide 0.25 or 0.5 mg

auxiliary substances: Polysorbate 80 sodium chloride sodium citrate dihydrate citric acid monohydrate disodium edetate water for injection 

in vials made of PE low-density, welded in groups of 5 units, with a volume of 2 ml in a cardboard pack of 4 or 6 units or in cartons 6 units in cardboard box in 2 packs.

Description pharmaceutical form:

The fine suspension, almost white, almost odourless.

Pharmacokinetics:

After inhalation budesonide is adsorbed quickly, in adults the systemic bioavailability of budesonide after inhalation via nebuliser is approximately 15% of the total assigned dose.

Cmax in plasma is 3.5 nmol/l and is reached after 30 min after beginning of inhalation.

Binding to plasma proteins is 85-90%.

Vd is 3 l/kg.

Budesonide undergoes transformation with the participation of microsomal liver enzymes, primarily CYP3A4. The main metabolite 6-&beta-hydroxybudesonide and 16&alpha-hydroxyprednisolone virtually devoid of biological activity (100 times less than that of budesonide).

Excreted by the kidneys as metabolites — 70%, through the intestines — 10%. The systemic clearance of inhalation of the drug is 0.5 l/min, Systemic clearance of metabolites — 1.4 l/min.

T1/2 is about 2-2,8 h.

Description pharmacological action:

GCS with a pronounced local anti-inflammatory and antiallergic effects, budesonide increases the production of lipocortin, which is an inhibitor of phospholipase A2, inhibits the release of arachidonic acid, inhibits the synthesis of leukotrienes and PG, reduces the inflammatory exudation and production of cytokines, inhibits the migration of macrophages, reduces the intensity of infiltration processes of granulation, the formation of substances of chemotaxis (which explains the efficiency in reactions of delayed-type hypersensitivity), inhibits the release of fat cells mediators of inflammation (hypersensitivity reaction immediate type).

Budesonide restores the sensitivity of the patient to bronchodilators, allowing to reduce the frequency of their use, reduces swelling of mucous membrane bronchi, production of mucus, the formation of phlegm and reduces Hyper-reactivity of the Airways. Increases mukotiliarnyi transport. Well tolerated in long-term care, has no mineralocorticoid 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 are effective in preventing attacks of bronchial asthma of physical exertion, but not relieves an acute attack of bronchospasm.

Indications:

treatment of bronchial asthma (basic therapy with insufficient effectiveness &beta2-agonists to reduce the dose of oral corticosteroids) in the case of ineffectiveness or inability to use the budesonide inhaler, drug delivery to the Airways or the inhaler that contains the drug in powder form

the treatment of COPD.

Contraindications:

• hypersensitivity to budesonide or any component of the drug
• children’s age (up to 12 months).

Caution: pulmonary tuberculosis, fungal, bacterial, parasitic and viral infections of the respiratory system, cirrhosis of the liver, pregnancy, lactation.

Application of pregnancy and breast-feeding:

The use of budesonide during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. If you want to use the drug is used in the minimum effective dose.

Data on the allocation of budesonide in breast milk are missing. The appointment of the drug during lactation is possible only under medical supervision in the case when expected benefit for mother exceeds the possible risk to the child.

Side effects:

Often (&ge1/100 but <1/10) — irritation and dryness of the mucous membrane of the pharynx, oral thrush, hoarseness, cough, dry mucous membranes of the mouth, unpleasant taste sensations.

Rarely (&ge1/10 000 but <1/1 000) — nervousness, anxiety, depression, behavioral disorders, hypersensitivity reactions of immediate and delayed actions (including rash, contact dermatitis, urticaria, angioedema and bronchospasm), skin bruising or thinning of the skin, headache, nausea, esophageal candidiasis.

When inhaled GCS may occur systemic effects, especially with prolonged treatment with high doses. The likelihood of such effects is much less than in the treatment of glucocorticoid for oral administration. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.

The drug budinich of STERI-Sky contains 0.1 mg/ml disodium edetate, which can cause bronchoconstriction at concentrations above 0.2 mg/ml.

As with other inhalation therapy, and may occur paradoxical bronchospasm, with fast increased shortness of breath after dosing. In case of severe reactions, you need to assign an alternative therapy.

In some cases, there is irritation of the skin when using a nebulizer with a mask. To prevent irritation after applying the mask the skin should be washed with water.

Drug interactions:

Pharmaceutical: the drug budinich of STERI-Sky can be mixed with 0.9% sodium chloride solution and other solutions designed for use with nebulizers, such as terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or the ipratropium bromide.

Pharmacological: the metabolism of budesonide is primarily carried out with the participation of isoenzyme CYP3A4. Receiving 100 mg of ketoconazole 2% a day increases the plasma concentration of oral budesonide used 10 mg once on average 7.8 times. Information about such interaction with inhaled dosage forms of budesonide is missing, however, one should expect a marked increase in the drug concentration in plasma, therefore, such inhibitors of CYP3A4 as ketoconazole and Itraconazole, may increase systemic exposure to budesonide. Other strong inhibitors of CYP3A4 probably also can significantly increase the concentration of budesonide in plasma.

Preliminary inhalation &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 microsomal liver enzymes).

Methandienone, estrogens increase the effect of budesonide.

Method of application and dose:

Inhaled using inhalers-nebulizers (see “Special instructions”, sub-section “technology use”).

The recommended dose of the drug in the event inhaled corticosteroids therapy in severe asthma, as well as on the background dose reduction or withdrawal of oral corticosteroids, the following:

Adults (including elderly) and children over 12 years: 1-2 mg 2 times per day. Supporting dose is 0.5–4 mg/day.

Children 12 months to 12 years: 0.25–0.5 mg 2 times a day. The maintenance dose is 0.25–2 mg/day.

The maintenance dose must be individualized. Upon reaching the therapeutic effect of maintenance dose must be reduced to the lowest effective dose.

Adults (including elderly) and children over 12 years: 0.5–1 mg 2 times a day.

Children 12 months to 12 years: 0.25–0.5 mg 2 times a day.

If necessary to achieve additional therapeutic effect, can be recommended to increase the dose budinich of STERI-Sky instead of a combination with oral corticosteroids (to reduce the risk of development of systemic effects).

The table below shows the conversion of doses for patients receiving oral corticosteroids in terms of budesonide.

Table

The dose of budesonide, taken by mouth, mgVolume of budesonide, 0.5 mg/2 ml (0.25 mg/ml), mlVolume of budesonide 1 mg/2 ml (0.5 mg/ml), ml0,251–0,5210,753–1421,563284

Overdose:

In acute overdose budesonide of clinical manifestations usually does not occur.

Treatment: cancel the drug, inhalation of bronchodilator are short-ranged vehicles.

With extended use at doses greater than recommended, may develop a systemic corticosteroids-the effect of hypercortisolism and suppression of adrenal function.

Special instructions:

The drug budinich of STERI-Sky is not intended for quick relief of asthma attacks. For the relief of acute bronchospasm it is recommended to use bronchodilator agents inhalacin short-acting.

Patients not receiving corticosteroids

Usually, the therapeutic effect occurs within 10 days. In patients with excessive secretion of mucus in the bronchi may initially be held short (about 2 weeks) additional treatment with oral corticosteroids. After a course of oral therapy in many cases completely stop taking GKS inside.

Patients under GCS therapy

Before transferring a patient to treatment with oral corticosteroids in the treatment of drug budinich of STERI-Sky condition of the patient must be relatively stable, then the drug budinich of STERI-Sky used in combination with the previously used dose of corticosteroids for oral administration for about 10 days. In subsequent dose of oral corticosteroids should be gradually lowered (for example 2.5 mg prednisolone or the equivalent each month) as possible to the lowest level. In most cases, oral corticosteroids may be completely replaced by the drug budinich of STERI-Sky.

Sometimes, during the transfer from treatment with glucocorticoids for oral administration for the treatment of drug budinich of STERI-Sky, observed symptoms (e.g. rhinitis, eczema and muscle and joint pain) who had previously stoped taking systemic drugs. The appearance of symptoms such as fatigue, headache, nausea and vomiting may indicate the development of systemic failure of GKS. In such cases, it may even be necessary to temporarily increase the dose of oral corticosteroids.

Systemic side effects of inhaled corticosteroids may occur first of all at introduction of high doses for an extended period of time. The likelihood of this effect is much smaller than in the treatment of oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. It is therefore important to titrate the dose of inhaled corticosteroids to the lowest dose at which effective control is maintained of the disease. It is recommended to regularly monitor the growth of children receiving inhaled corticosteroids for prolonged period of time. In the case of stunting should be performed correction treatment to reduce the dose of inhalation corticosteroids to the lowest dose at which effective control is retained bronchial asthma.

Oral ketoconazole and Itraconazole or other CYP3A4 inhibitors causes an increase in systemic exposure to budesonide. Therefore, if necessary, the joint use must be taken with a maximum interval. You should also consider the possibility of reducing the dose of budesonide.

To minimize the risk of fungal disease, you should inform the patient and/or parents of the child about the need to rinse your mouth with water after each inhalation drug.

Effects on ability to drive a vehicle and operate machinery. The drug budinich of STERI-Sky has no adverse effect on the ability to drive a vehicle and operate machinery. In the case of rare adverse reactions from the nervous system you should avoid activities that require speed of psychomotor reactions.

The technique of using

Ultrasonic nebulizers are unsuitable for use with the drug budinich of STERI-Sky the patient requires, the dose may vary depending on the used nebulizer. The time of inhalation and the dose depend on the speed of the air flow, the chamber volume of the nebulizer, and filling volume. Therefore, inhalation of the drug budinich of STERI-Sky you must use the appropriate nebulizer and mouthpiece and a face mask. The nebulizer must be connected to air compressor to create the appropriate air flow.

Before using the drug you must read the manufacturer’s manual nebulizers.