Composition, form of production and packaging
Aerosol for inhalation is dosed in the form of a suspension of white or almost white color.
1 dose
salmeterol xinafoate 36.3 Ојg,
which corresponds to a salmeterol content of 25 Ојg
fluticasone propionate 50 Ојg
[PRING] 1,1,1,2-tetrafluoroethane (HFA-134a) - 73.099 mg, polyethylene glycol 1000 - 0.01464 mg.
120 doses - aerosol cans of aluminum (1) with dosing valve and mouthpiece - packs of cardboard.
Aerosol for inhalation is dosed in the form of a suspension of white or almost white color.
1 dose
salmeterol xinafoate 36.3 Ојg,
which corresponds to a salmeterol content of 25 Ојg
fluticasone propionate 125 Ојg
[PRING] 1,1,1,2-tetrafluoroethane (HFA-134a) - 73.024 mg, polyethylene glycol 1000 - 0.01464 mg.
120 doses - aerosol cans of aluminum (1) with dosing valve and mouthpiece - packs of cardboard.
Aerosol for inhalation is dosed in the form of a suspension of white or almost white color.
1 dose
salmeterol xinafoate 36.3 Ојg,
which corresponds to a salmeterol content of 25 Ојg
fluticasone propionate 250 Ојg
[PRING] 1,1,1,2-tetrafluoroethane (HFA-134a) - 72.9 mg, polyethylene glycol 1000 - 0.01464 mg.
120 doses - aerosol cans of aluminum (1) with dosing valve and mouthpiece - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Salmecort is a combined bronchodilator (contains salmoterol and fluticasone propionate). Salmeterol is a selective beta 2- adrenoreceptor agonist of long-term action (at least 12 h). The salmeterol molecule has a long side chain that binds to the outer domain of the receptor. Due to these pharmacological properties, salmeterol is more effective in preventing histamine-induced bronchoconstriction and causes longer bronchodilation in comparison with conventional short-acting beta- 2 receptor agonists. Effectively and long-term inhibits the release in the lung tissues of mediators of mast cells, such as histamine, leukotrienes and PgD 2 . Suppresses early and late stage of allergic reaction; after the introduction of a single dose, the hyperreactivity of the bronchi decreases, the inhibition of the late stage persists for more than 30 hours after taking a single dose, when the bromine-lowering effect is no longer present.
Fluticasone propionate-GKS local action. When inhaled in the recommended doses has a pronounced anti-inflammatory and antiallergic effect, which leads to a decrease in the severity of symptoms and a decrease in the frequency of exacerbations of diseases accompanied by airway obstruction. With prolonged use of inhalation fluticasone propionate at the maximum doses, the daily and reserve secretion of adrenal cortex hormones remains within the normal range in adults and children. The residual reduction in the reserve function of the adrenal gland can persist for a long time after the therapy.
PHARMACOKINETICS
There is no evidence that joint inhalation administration of salmeterol and fluticasone propionate affects the pharmacokinetics of each of these substances. Salmeterol: after inhalation in therapeutic doses, very low concentrations of the drug in the blood plasma are created (200 pg / ml or less). With regular use of inhaled salmeterol in the systemic blood stream, hydroxynaphthoic acid is determined in concentrations up to 100 pg / ml.
Fluticasone propionate: after inhalation, the relative bioavailability is 10 to 30%, depending on the drug delivery system. Systemic absorption occurs in the advantage of nude in the lungs. Part of the inhaled dose may be swallowed, but its systemic effect is minimal due to the poor solubility of the drug in water and intensive metabolism when "first passed" through the liver. The bioavailability of fluticasone upon ingestion is less than 1%. There is a direct relationship between the magnitude of the inhaled dose and the systemic effect of fluticasop, the volume of distribution is about 300 liters . Metabolized in the liver to an inactive metabolite involving the CYP3A4 system of cnthochrom P450. Less than 5% of the metabolite is excreted in the urine. The plasma clearance is 1.15 l / min. T 1/2 about 8 hours.
INDICATIONS
Salmecort is intended for regular treatment of bronchial asthma in patients who are shown combined therapy with long-acting beta 2 -adrenomimetik and inhaled glycocorticosteroid:
- in patients with insufficient control of the disease against the background of constant ionotherapy with inhaled glucocorticosteroids with periodic use of beta 2 -adrenomimetics of short-acting;
- in patients with adequate disease control on the background of therapy with inhaled glucocorticosteroid and long-acting beta 2 -adrenomimetics;
- as a starting maintenance therapy in patients with persistent asthma (daily occurrence of symptoms, daily use of funds for rapid relief of symptoms) in the presence of indications for the appointment of glucocorticosteroids to achieve control of the disease;
- Supportive therapy in patients with COPD who have a forced expiratory volume (FEV1) value of <60% of the required values ​​(prior to bronchodilator inhalation) with repeated exacerbations in the anamnesis, and in which the symptoms of the disease persist despite regular therapy
bronchodilators.
DOSING MODE
Inhalation. Only for inhalation.
The patient should be informed that to obtain the optimal effect the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD.
The physician should regularly evaluate the effectiveness of the patient's treatment. Determining the duration of the course of therapy and changing the dose of the drug is possible only on the advice of a doctor. The initial dose of the drug is determined based on the dose of fluticasone, which is recommended for the treatment of a disease of a given severity. Then the initial dose should be gradually reduced to the lowest effective dose. During treatment should be observed regularly with a doctor in order to select the optimal dose. The patient should not independently change the dose prescribed by the doctor.
Bronchial asthma
If taking Salmecort twice a day provides control over the symptoms, reducing the dose to the lowest possible dose can reduce the frequency of taking the drug up to 1 time / day.
The patient should be prescribed a form of Salmecort, which contains a dose of fluticasone propionate, corresponding to the severity of his disease. If inhaled GCS therapy does not provide adequate control over the disease, their replacement with Salmecort at a dose therapeutically equivalent to that administered by GCS can improve the control of asthma. In patients who can monitor the course of asthma solely with inhaled glucocorticosteroids, their replacement with Salmecort may help reduce the dose of GCS needed to control asthma.
Recommended doses
Adults and children aged 12 years and over:
- two inhalations (25 mcg salmeterol and 50 mcg fluticasone propiopate) 2 times / day, or
- two inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times / day, or
- two inhalations (25 Ојg of salmeterol and 250 Ојg of fluticasone proionioate) 2 times / day.
Children aged 4 years and over:
- two inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times / day.
All patients taking the drug as maintenance therapy should undergo a doctor's consultation 6-12 weeks after the initial admission.
Chronic obstructive pulmonary disease
For adult patients, the maximum recommended dose is 2 inhalations (25 Ојg salmeterol and 250 Ојg fluticasone propionate) 2 times / day.
Special patient groups
There is no need to reduce the dose of Salmecort in elderly patients, as well as in patients with impaired renal or hepatic function.
Instructions for use of the inhaler
Before each use, the inhaler should be shaken.
Checking the inhaler
1. Before the first application or if the inhaler has not been used for 2 days or more, it is necessary to check the inhaler. To do this, hold 4 strokes (inhalation) in the air.
Use of an inhaler
2. Remove the protective cover from the mouthpiece. In doing so, the mouthpiece must remain tightly attached to the vial (inhaler); If the inhaler was stored without a protective cover, it is necessary to check the mouthpiece for contamination.
3. Take the inhaler in the hands of the mouthpiece downwards so that one finger is on the bottom of the inhaler, and the other finger or two on the upper end of the inhaler. Exhale and place the mouthpiece between the teeth.
4. Tightly grasp the mouthpiece with your lips and slightly tilt your head back. Slowly start inhaling and simultaneously press the bottom of the can. Continue inhaling to the end.
5. Remove the inhaler from the oral cavity and hold your breath for 10 seconds or as much as it is comfortable. Slowly exhale.
Note:
After each inhalation, rinse mouth and / or throat with water. This will help reduce the dryness associated with taking the drug. The interval between inhalations should be at least 1 min. When re-inhalation is repeated, repeat steps 2-5. After use, close the mouthpiece with a protective cap.
The first few inhalations are recommended to be carried out by controlling yourself in front of the mirror. If you see that there is a "leakage" of the drug through the mouth or out of the hole between the mouthpiece and the body of the inhaler, this is evidence of an incorrect technique of inhalation.
Inhalations for young children should be carried out under the supervision of an adult.
Older children and adults with weak arms should hold the inhaler with both hands. Thus both index fingers should settle down on the top part of an inhaler, and both greater fingers - on the basis below a mouthpiece.
Cleaning the inhaler
Cleaning of the inhaler should be carried out at least 1 time / day.
1. Remove the metal can with the preparation from the body of the inhaler. Remove the spray tip.
2. Wash the mouthpiece and body of the inhaler under warm running water.
3. Thoroughly wipe with a dry cloth or cotton swab. Do not overheat.
4. Assemble the inhaler.
After using all the doses indicated on the package, the metal canister should be discarded.
SIDE EFFECT
All the undesirable reactions presented below are characteristic for the active substances - salmeterol and fluticasone propionate alone. The safety profile of Salmecort does not differ from the profile of undesirable reactions of its active ingredients.
The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (? 1/10), often (? 1/100 and <1/10), infrequently (? 1/1000 and <1/100), rarely (? 1/10000 and <1 / 1000), very rarely (<1/10000, including individual cases).
Infections and invasions: often - candidiasis of the mouth and pharynx, pneumonia (in patients with COPD).
Disorders from the immune system: infrequent - skin reactions hypersensitivity; rarely - anaphylactic reactions, angioedema, mainly edema of the face and oropharynx, bronchospasm.
Disorders from the endocrine system: possible systemic effects include (see the sections "With caution" and "Special instructions"), rarely - Cushing's syndrome, Cushing's symptoms, suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density;
Disturbances from the organs of vision: infrequently - cataract; rarely - glaucoma.
Disorders from the metabolism and nutrition: infrequently - hyperglycemia; very rarely - hypokalemia.
Disorders of the psyche: infrequently: anxiety, sleep disturbances; rarely - changes in behavior, incl. increased activity and irritability (especially in children).
Violations from the nervous system: very often - headache (see section "Special instructions"); infrequently - a tremor (see section "Special instructions").
Violation of the heart: infrequent - rapid heartbeat (see "With caution" and "Special instructions"), tachycardia, atrial fibrillation; rarely - arrhythmia, including ventricular extrasystole, supraventricular tachycardia, extrasystole.
Disturbances from the respiratory system, chest and mediastinal organs: often - hoarseness of voice and / or dysphonia; infrequent - pharynx irritation; rarely - paradoxical bronchospasm (see section "Special instructions").
Disturbances from the skin and subcutaneous tissues: infrequent - bruising.
Disturbances from the skeleton-muscular system and connective tissues: often - muscle spasms, arthralgia.
Disorders from the side of the .LC: very rarely - dyspepsia, nausea.
Children and teens
It is theoretically possible to develop systemic reactions involving Cushing syndrome, Cushingoid symptoms, suppression of adrenal function, growth retardation in children and adolescents. Very rarely there may be anxiety, sleep disorders and behavioral disorders, including hyperactivity and irritability.
CONTRAINDICATIONS
hypersensitivity to one or more of the components of the drug;
- Children's age (up to 4 years).
Carefully
Like all other inhaled preparations containing glucocorticosteroids, Salmecort should be used with caution in patients with acute or latent pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, with thyrotoxicosis.
When taking any preparations of the group of sympathomimetics, especially when therapeutic doses are exceeded, it is possible to develop cardiovascular events such as an increase in systolic blood pressure and heart rate. For this reason, Salmecort should be administered with caution to patients suffering from cardiovascular diseases, incl. with arrhythmias, such as supranventicular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation.
All sympathomimetic drugs in dosages exceeding therapeutic may cause a transient decrease in potassium levels in the blood serum, therefore, the Salmecort drug should be used with caution in patients with hypokalemia. Any inhaled GCS can cause systemic effects, especially with prolonged use in high doses, so the drug should be used with caution in glaucoma, cataracts, and osteoporosis (see section "Special instructions and precautions for use").
There are very few reports of an increase in blood glucose, so patients with diabetes should use Salmecort with caution (see section "Side effect").
PREGNANCY AND LACTATION
Pregnant women and women should be prescribed lactation only if the expected benefit to the mother exceeds any possible risk to the fetus or child.
There is insufficient data on the use of salmetrotrol and fluticasone propionate in pregnancy and lactation.
Pregnancy
Excessive systemic concentration of active beta 2 -adrenomimetic and GCS affects the fetus.
The extensive clinical experience of using this class of drugs indicates that when using therapeutic doses, the described effects are not clinically significant. Salmeterol and fluticasone propionate do not possess genotoxicity.
Lactation
The concentration of salmeterol and fluticasone propionate in blood plasma after inhaling the drug in therapeutic doses is extremely low, so their concentration in breast milk should be the same low. There is no data on the concentration of salmeterol and fluticasone propionate in breast milk of women during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
There is no need to reduce the dose of Salmecort in patients with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
There is no need to reduce the dose of Salmecort in patients with impaired liver function.
APPLICATION FOR CHILDREN
The use of the drug for children under the age of 4 years is contraindicated.
APPLICATION IN ELDERLY PATIENTS
There is no need to reduce the dose of Salmecort in elderly patients.
SPECIAL INSTRUCTIONS
Salmecort is not intended to alleviate acute symptoms, because in such cases, a rapid and short-acting inhaled bronchodilator (eg, salbutamol) should be used. Patients should be informed that they always have at hand a drug to stop acute symptoms. The combination of salmeterol and fluticasone propionate can be used for initial maintenance therapy in patients with persistent asthma (daily occurrence of symptoms or daily use of an agent for arresting seizures), if there is evidence of SCS administration and when determining their approximate dosage.
The more frequent use of short-acting bronchodilators to relieve symptoms indicates a worsening of control over the disease, and in such situations the patient should consult a doctor.
The sudden and increasing deterioration in the control of bronchial asthma poses a potential threat to life, and in such situations, the patient should also consult a doctor. The doctor should consider the possibility of a higher dose of GCS. If the dose of Salmecort used does not provide adequate control over the disease, the patient should also consult a doctor.
Patients with asthma can not dramatically reduce the treatment with Salmecort because of the danger of aggravation, the dose of the drug should be reduced gradually under the supervision of a doctor. In patients with COPD, removal of the drug may be associated with symptoms of decompensation and requires medical supervision.
COPD patients receiving the drug Salmekort may increase the incidence of pneumonia (see. Section "Side effects"). Physicians should be aware of the possibility of pneumonia in patients with COPD as the clinical picture of an exacerbation of COPD and pneumonia are often similar.
Any inhaled corticosteroids can cause systemic reactions, especially with prolonged use at high doses; but the likelihood of such symptoms are much lower than in the treatment with oral corticosteroids (see. section "Overdose"), the possibility of systemic effects include Cushing's syndrome, cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. Therefore, the treatment of asthma it is important to reduce the dose to the lowest dose that provides effective control of the disease.
In emergency and planned situations that can cause stress, you should always keep in mind the possibility of adrenal suppression and be ready to use corticosteroids (see. "Overdose" section).
During resuscitation or surgical procedures require a degree of nadnochechnikovoy failure. It is recommended to regularly measure the growth of children who receive long-term therapy with inhaled glucocorticosteroids.
Because of the possibility of adrenal suppression, patients transferred from oral corticosteroids to inhalation therapy of fluticasone propionate. It should be treated with extreme caution and regular monitoring of their function of the adrenal cortex. When transferring patients receiving systemic corticosteroids allergic reactions can manifest themselves in inhalation therapy (e.g., allergic rhinitis, eczema), which previously suppressed systemic corticosteroids. In situations podobnth recommended symptomatic treatment with antihistamines and / or topical preparations, including GCS for topical application.
After initiation of treatment with inhaled fluticasone propionate systemic corticosteroids should be lifted gradually, and such patients should be in possession of a special patient card, containing an indication of the possible need for additional administration of corticosteroids in stressful situations.
In patients with acute exacerbation of asthma, hypoxia necessary to control the concentration of potassium ions K + , and plasma.
There are very rare reports of increased blood glucose levels, and this should be borne in mind when assigning the combination of salmeterol with fluticasone propionate in patients with diabetes mellitus (see. Section "Side effects").
Due to the possibility of systemic effects of corticosteroids, including Cushing's syndrome and adrenal suppression, should avoid joint use of fluticasone propionate and ritonavir, except in cases where the potential benefit to the patient outweighs the risk associated with systemic GCS effects (see. Section "Interaction with other medicines ").
When receiving salmeterol risk of serious adverse reactions in the respiratory system and death in African-American patients, presumably, higher than in other patients. The value of pharmacogenetic factors or other unknown reasons. Effect of concomitant use of inhaled corticosteroids on the risk of death in patients with asthma has not been studied.
Like other inhalants, Salmekort may cause paradoxical bronchospasm, increase of manifesting dyspnea directly after application.
In this case, you should immediately apply fast- and short-inhaled bronchodilator, cancel Salmekort and start, if necessary, alternative therapy (see. Section "Side effects").
May experience adverse reactions associated with the pharmacological action of beta 2 -receptor. such as tremor, subjective feeling of palpitations and headache. However, these reactions are of short duration, and their severity decreased at regular therapy (see. The section "Side effect").
Influence on ability to drive vehicles, mechanisms
In clinical studies, no evidence on the effect of the drug on the ability to drive vehicles and other mechanisms, but consider the side effects, which can cause the drug.
OVERDOSE
We do not recommend use of the drug in doses higher than those specified in the "Method of use and dosage." It is important to regularly review the patient's dosage regimen and reduce the dose to the lowest of the recommended doses for ensuring effective control of the disease ( "Dosage and administration").
Symptoms
Expected signs and symptoms of salmeterol overdose are typical of excessive beta 2adrenergic stimulation, and include tremor, headache, tachycardia, increased systolic blood pressure and hypokalaemia. Acute overdose of fluticasone propionate when inhaled can cause a temporary suppression of the hypothalamic-pituitary-adrenal system. it does not usually require the adoption of any emergency measures, as normal adrenal function is recovered in a few days.
Before the drug in doses higher than those recommended for a long period of time may be a significant inhibition of adrenocortical function. Described rare cases of acute adrenal crisis, which occurred mostly in children treated with doses higher than the recommended for a long time (months or years). Acute adrenaline crisis manifested hypoglycemia accompanied by confusion and / or convulsions. Situations which may serve as a triggering factor acute adrenal crisis include trauma, surgery, infection or any rapid reduction in the dose of inhaled fluticasone propionate included in the composition Salmekort preparation.
Treatment
No specific treatment of overdosage of salmeterol and fluticasone propionate. In case of overdose should be supportive therapy and observe the patient's condition.
In applying the drug in doses higher than those specified in the instructions for a long time, there may be suppression of adrenocortical function.
DRUG INTERACTION
Because of the risk of bronchospasm should avoid the use of selective and nonselective beta-blockers except in cases where they are essential to the patient.
Salmeterol
concomitant use of ketoconazole should be avoided unless the benefits of the application does not exceed the potential risk of systemic adverse reactions in the treatment of salmeterol. There is a similar risk of interaction with other potent inhibitors of CYP3A4 (itraconazole, telithromycin, ritonavir).
fluticasone propionate
In normal situations inhalation the fluticasone propionate are accompanied by low concentrations in plasma due to the extensive metabolism of the "first pass" and the high systemic clearance influenced isoenzyme CYP3A4 of cytochrome P450 in the gut and liver. Due to this clinically significant interactions involving fluticasone propionate are unlikely.
Ritonavir is an inhibitor of highly active CYP3A4 enzyme may cause a sharp increase in the concentration of fluticasone propiopata plasma, thereby substantially decreasing the concentration of serum cortisol. Joint application with ritanovir causes side effects such as Cushing's syndrome, and adrenal suppression. Considering the above, it should avoid the simultaneous use of fluticasone propionate and ritanovir unless the potential benefit to the patient outweighs the risk of systemic side effects of corticosteroids.
Other inhibitors of CYP3A4 isoenzyme cause negligible (erythromycin) and minor (ketoconazole) increase the content of fluticasone propionate in plasma, in which almost no decrease in serum cortisol concentrations. Despite this, it is advisable to be careful while applying strong inhibitors of CYP3A4 (e.g., ketoconazole), since under such combinations are not excluded increasing the concentration of fluticasone propionate in plasma.
Xanthine derivatives, corticosteroids and diuretics increase the risk of hypokalemia (especially in patients with acute exacerbation of bronchial asthma, during hypoxia). MAO inhibitors and tricyclic antidepressants increase the risk of side effects of the cardiovascular system. Compatible with kromoglitsievoy acid.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in reach of children at a temperature not higher than 25 В° C, do not freeze. Shelf life - 2 years.
Do not use the drug after the expiration date.
