Foster

General characteristics. Structure:

Active agents: the formoterola fumarates 0,006 mg; beclomethasone Dipropionas of 0,100 mg

Excipients: ethanol, Acidum hydrochloricum, норфлуран (1,1,1,2-tetraftoretan).

Pharmacological properties:

Foster contains beclomethasone Dipropionas and формотерол, the having various mechanisms of action and frequencies of exacerbations of bronchial asthma showing the additive effect concerning decrease.
Beclomethasone Dipropionas - inhalation глюкортикостероид (GKS), in the recommended doses has antiinflammatory effect, reduces expressiveness of symptoms of bronchial asthma and reduces the frequency of exacerbations of a disease, at the same time has the smaller frequency of side effects, than system GKS.
Formoterol - the selection agonist of beta2-adrenergic receptors causing relaxation of smooth muscles of bronchial tubes in patients with reversible obstruction of respiratory tracts. Broncholitic action comes quickly, within 1-3 min. after inhalation, and remains during 12 h after inhalation of a single dose.
Addition of a formoterol to beclomethasone to Dipropionas reduces expressiveness of symptoms of bronchial asthma, improves indicators of the function of external respiration (FER) and reduces the frequency of exacerbations of a disease. During clinical trial it was shown that influence on FVD of the fixed combination Foster corresponds to that a combination of monodrugs of beclomethasone of Dipropionas and a formoterol and exceeds effect of one beclomethasone of Dipropionas.

Pharmacokinetics. Pharmacokinetic indicators for the corresponding HP were comparable after purpose of beclomethasone of Dipropionas (BJP) and a formoterol in the form of monodrugs and as a part of the combined drug.
For Dipropionas beclomethasone at introduction as a part of the combined drug AUC for its active metabolite of beclomethasone-17-monopropionate and the size of the maximum concentration in plasma (Cmax) is slightly lower, and absorption happens quicker, than at Dipropionas beclomethasone monodrug.
For a formoterol at introduction as a part of the combined drug Cmax in plasma matched that for monodrug, and systemic action was slightly higher, than at monodrug.
Data on pharmacokinetic or pharmakodinamichesky interaction between BJP and formoteroly are not obtained:

Beclomethasone Dipropionas
BJP under the influence of esterase turns into an active metabolite beclomethasone-17-monopropionate (V-17 MP).
Inhalated by BJP quickly it is absorbed by lungs; its absorption is preceded by intensive conversion of BJP in its active metabolite of beclomethasone-17-monopropionate (V-17 MP). System bioavailability (V-17 MP) is provided for 36% at the expense of lungs, and also due to absorption by bodies of the digestive tract (DT) of the swallowed part of an inhalation dose. Bioavailability swallowed by BJP it is insignificant it is small, however, presystem conversion of BJP in V-17 MP leads to the fact that 41% of BJP are acquired by an organism in the form of V-17 MP. Almost linear increase in systemic action at increase in an inhalation dose is observed. Absolute bioavailability after inhalation makes about 2% and 62% of a nominal dose in relation to not changed BJP at and V-17 MP, respectively.
Communication with proteins of plasma rather high.
Metabolism
BJP is characterized by very high rate of clearance from a big circle of blood circulation due to effect of the esterase which is present at the majority of fabrics. A key product of metabolism of BJP - an active metabolite of V-17 MP. Less active metabolites are beclomethasone 21 monopropionate (V-21 MP) and beclomethasone (WONS) which are also formed as a result of metabolism, but their role in system influence of BJP is very insignificant.
Excretion
The main part of BJP is removed with a fecal masses in the form of polar metabolites. Renal excretion of BJP and its metabolites is insignificant. The elimination half-life (T1/2) of BJP and V-17 of MP makes the 0,5 and 2, 7 hour, respectively.
Special population
The liver failure does not lead to change of pharmacokinetic properties and a profile of safety of BJP because the last is exposed to bystry metabolism to polar metabolites of V-21 MP, WONS and V-17 MP under the influence of the enzymes which are present at digestive tract, a blood plasma, lungs and a liver.
Pharmacokinetic properties of BJP at the patients having a renal failure were not studied. In view of that both BJP, and its metabolites with urine are practically not allocated, there are no bases to assume strengthening of systemic action of drug on an organism of the patients having a renal failure.

Formoterol
Absorption and distribution
Inhalated формотерол it is absorbed in lungs and a GIT. A part of an inhalation dose which is swallowed depends on type of the inhalation device and technology of inhalation. So when using of the multidose dosed inhaler it can make up to 90%. Therefore the swallowed fraction needs to be considered at an inhalation way of administration of drug.
Not less than 65% of a peroral dose of a formoterol are soaked up through a GIT, at the same time 70% of this volume are exposed to presistemny metabolism. The maximum concentration of not changed formoterol in a blood plasma is observed during 0,5-. 1 hour after oral administration. Communication with proteins of plasma at a formoterol makes 61-64%, at the same time affinity to albumine - 34%. In the range of therapeutic doses of saturation of affinity it is not observed. At oral administration of T1/2 makes 2-3 hours. At inhalation of 12-96 mkg of a formoterol of a fumarat absorption of a formoterol has linear character.
Metabolism
Metabolism of a formoterol is carried out, in particular, due to direct conjugation of fenolgidroksilny group.
Conjugates of glucuronic acid are not active. The second significant way of metabolism of a formoterol - O-dimetelirovaniye by means of conjugation at the level of phenol-2-hydroxylic group. P450 cytochrome of CYP2D6, CYP2C9, CYP2C19 enzymes participates in O-demetelirovanii a formoterola. There are bases to assume that metabolism of a formoterol is carried out, mainly, in a liver. Formoterol does not inhibit CYP450 enzymes in therapeutic significant concentration.
Excretion
Total renal excretion of a formoterol after inhalation of a single dose through the Dosed powder inhaler increases linearly in the range of doses of 12-96 mkg. Indicators of excretion of not changed and general formoterol, on average, make 8 and 25%, respectively. On the basis of measurements of plasma concentration of a formoterol after its single inhalation in a dose of 120 mkg at 12 healthy volunteers T1/2 which made 10 hours was defined. A ratio (R, R) - and (S, S) - enantiomer of not changed drug at renal excretion makes respectively, 40 and 60%. The relative ratio of these 2 indicators does not change in the range of the studied dosages; there is no evidence of accumulation of one enantiomer concerning another after reception, a repeated dose.
At healthy volunteers after oral administration (40-80 mkg) of 6-10% of a dose it was revealed in urine in the form of not changed drug; 8% of a dose were present at a type of glucuronides.
Only 67% of a peroral dose of a formoterol are removed by kidneys (preferential in the form of metabolites), other part of a dose - through intestines. The renal clearance of a formoterol makes 150 ml/min.

Indications to use:

Basic therapy of the bronchial asthma providing purpose of a combination therapy (an inhalation glucocorticosteroid and β2-адреномиметика long action):
Patients, disease symptoms which are insufficiently controlled by inhalation glucocorticosteroids and β2-адреномиметиками short action;
The patients receiving effective maintenance doses of inhalation glucocorticosteroids and β2-адреномиметиков long action.

Route of administration and doses:

Foster is not intended for initial treatment of bronchial asthma. Selection of a dose of the drugs which are Foster's part happens individually and depending on severity of a disease. It needs to be considered not only at an initiation of treatment the combined drugs, but also at change of a maintenance dose of drug If certain patients need other combination of doses of active components, than in Foster, it is necessary to appoint β2-adrenomimetik and/or glucocorticosteroids in separate inhalers.
For adults and teenagers 12 years are more senior:
1-2 inhalations twice a day. Patients have to be under constant control of the doctor for adequate selection of a dose Foster. The dose should be lowered to the smallest against the background of which optimum control of symptoms of bronchial asthma remains. At achievement of complete control over symptoms of bronchial asthma against the background of the minimum recommended drug dose, at the following stage it is possible to try purpose of monotherapy by inhalation glucocorticosteroids.
There is no need for special selection of a dose of drug for patients of advanced age. There are no data on Foster's reception by patients with a renal or liver failure.
Application instruction of an inhaler.
The patient it is necessary to teach to use correctly an inhaler and to periodically check technology of performing inhalation.
Before the first use of an inhaler or in 3 days and more after a break in its use the first dose needs to be sprayed in air to be convinced that it works.

Take an inhaler big and index fingers.
Remove a protective cap from an inhaler mouthpiece.
Take a mouthpiece in a mouth, having densely clasped it with lips, and completely exhale through a nose.
Make a long deep breath, having at the same time made pressing a barrel end face an index finger.
After a breath as long as possible hold the breath. Then take out a mouthpiece from a mouth and continue to breathe normally.

For receiving the second dose, keeping an inhaler in vertical position, wait for about 30 seconds and then repeat stages with 3 on 5.
After use densely close a mouthpiece a protective cap.
Attention! Completing phases 3 and 4, it is impossible to hurry. It is necessary to begin a breath as it is possible more slowly, just before pressing the inhaler valve.
If gas partially comes out an upper part of an inhaler or corners of a mouth of the patient, it is necessary to repeat the sequence of operations, since a stage 3.
With weak hands it is more convenient to patients to hold an inhaler with two hands. Therefore, it is necessary to hold an upper part of an inhaler two index fingers, and its lower part - thumbs.
After inhalation it is recommended to rinse a mouth water.
For maintenance of purity of a mouthpiece it is recommended to wash out it warm water in process of pollution.
There are no clinical data on Foster's use with a spacer; therefore the recommended dosage of drug is given taking into account that the inhaler without spacer with the standard activator is used.
It must be kept in mind that when using Foster's with a spacer there can be a need for correction of a dose.

Features of use:

If at patients such associated diseases as coronary heart disease, a myocardial infarction, an aggravation of a course of arterial hypertension, disturbance of a cordial rhythm, chronic heart failure, a diabetes mellitus, a prostatauxe, glaucoma are observed, it is necessary to show extra care at the choice of a dose of Foster.
It is necessary to observe precautionary measures at treatment of patients with the extended QTc - an interval (QTc> 0,44 sec.). Reception of a formoterol can cause QTc lengthening - an interval. Foster can be used at patients with a tachyarrhythmia only at observance of special precautionary measures, such as monitoring of an ECG.
It is necessary to observe special precautionary measures at the patients with unstable bronchial asthma applying bronchodilators of short action to removal of attacks at an exacerbation of heavy bronchial asthma as the risk of development of a hypopotassemia increases against the background of a hypoxia and at other states when the probability of manifestation of development of gipokaliyemichesky effect increases. In such cases it is recommended to control the content of potassium in serum.
Inhalations of high doses of a formoterol can lead to increase in level of sugar in blood. During treatment it is necessary to control concentration of glucose in blood at the patients suffering from a diabetes mellitus. If anesthesia is planned by drugs of the halogenated hydrocarbons, it is necessary to warn the patient not to use Foster within 12 hours before anesthesia.
As well as at purpose of other GKS, it is necessary to reconsider need of use and Foster's dose at patients with active or inactive forms of a pulmonary tuberculosis, fungal, viral or bacterial infections of a respiratory organs.
Because of danger of development of an aggravation treatment by Foster cannot be stopped sharply, the dose of drug should be reduced gradually and under control of the doctor.
When patients already take this course of treatment (inhalation or peroral GKS), it needs to be continued without any changes even if improvement of symptoms is observed. Preservation of symptoms of bronchial asthma or need of increase in a dose of Foster can demonstrate deterioration in a course of bronchial asthma and need of review of treatment. For stopping of bad attacks of a bronchospasm patients are recommended to have constantly at themselves beta2-adrenomimetik of short action.
It is not necessary to appoint treatment by Foster in the period of an exacerbation of bronchial asthma.
As well as at any other inhalation therapy, emergence of a paradoxical bronchospasm with immediate strengthening of rattles after reception of a dose of drug is possible. In this connection, it is necessary to stop therapy by Foster, to reconsider tactics of treatment and, if necessary, to appoint alternative therapy.
Any inhalation GKS can cause system effects, especially at long use in high doses; it should be noted, however, that the probability of development of such symptoms is much lower, than at treatment by peroral GKS.
Possible system effects include oppression of function of adrenal glands, a growth inhibition at children and teenagers, decrease in mineral density of a bone tissue, a cataract and glaucoma. Considering told, the dose of inhalation GKS should be titrated to minimum which will provide maintenance of effective control.
At chronic reception of overdoses of beclomethasone of Dipropionas its systemic action can be shown: there can be a significant oppression of bark of adrenal glands up to adrenal crisis. Adrenal crisis is shown by anorexia, abdominal pains, weight reduction, fatigue, a headache, nausea, vomiting, hypotension, the hypoglycemia which is followed by confusion of consciousness. and/or spasms. The injury, surgical intervention, an infection or a bystry dose decline of the beclomethasone which is Foster's part belong to situations which can serve as starting factors of acute adrenal crisis. At chronic overdose it is recommended to carry out control of reserve function of bark of adrenal glands.
If there are bases to believe that against the background of the previous system therapy of GKS function of adrenal glands was broken, it is necessary to take precautionary measures at transfer of patients into treatment by Foster. Advantages of inhalation therapy by beclomethasone, as a rule, minimize need of reception of peroral GKS, however at the patients stopping therapy by peroral GKS, insufficient function of adrenal glands can remain for a long time. Patients who in the past needed urgent reception of high doses of GKS or received prolonged treatment by inhalation GKS in a high dose can also be in this risk group. It is necessary to provide additional purpose of GKS in the period of a stress or surgical intervention.
It is recommended to instruct the patient about need to rinse a mouth water after inhalations of maintenance doses for the purpose of prevention of risk of development of candidiasis of a mucous membrane of an oral cavity and a throat. The barrel is under pressure: not to subject to influence of high temperature, not to pierce, not to throw into fire, even empty. To use within 3 months since the beginning of use.

Side effects:

Foster contains beclomethasone Dipropionas and формотерол fumarates and therefore it is necessary to expect that it can cause the side effects characteristic of the specified components. There are no data that their simultaneous use causes additional side effects.
The side effects connected using beclomethasone of Dipropionas and a formoterol as the fixed combination (Foster) are given below.

Frequent (> 1/100, <1/10)	Central nervous system:	Headache
	Infections Respiratory tracts:	Pharyngitises voice osiplost
Less frequent (> 1/1000, <1/100)	Cardiovascular system:	Heartbeat, lengthening of an interval of QT, change of the electrocardiogram
	Integuments Skeletal and muscular system Infections	Hyperemia, inflows Tremor, muscular spasms Flu, candidiases of a mucous membrane of an oral cavity, throat and gullet, vaginal candidiasis, gastroenteritis, sinusitis
	Immune system	Allergic dermatitis; Increase in S-reactive protein
	System of blood	Granulocytopenia, increase in quantity of thrombocytes
	Respiratory system	Rhinitis, dysphonia, cough, slight irritation in a throat, a bronchospasm
	Digestive tract	Dryness in a mouth, burning sensation in lips, a dysphagy, dyspepsia, diarrhea
	Metabolic disturbances	Hypopotassemia

Among the most frequent side effects connected with reception of a formoterol are described such typical for beta2-adrenomimetik as: hypopotassemia, headache, tremor, heartbeat, cough, muscular spasms, lengthening of a QTc-interval. Side effects characteristic of Dipropionas beclomethasone: candidiasis of a mucous membrane of an oral cavity and throat, irritation in a throat.
As well as other inhalation drugs, Foster can cause a paradoxical bronchospasm.
Other side effects characteristic of a formoterol: thrombocytopenia, Quincke's disease, hyperglycemia, increase in content in blood of insulin, free fatty acids, glitserol and ketonic derivatives, sleep disorder, hallucinations, fatigue, concern, change of flavoring feelings (dysgeusia), tachycardia, tachyarrhythmia, ventricular premature ventricular contraction, stenocardia (coronary heart disease), fibrillation of auricles, arterial hypertension, arterial hypotension, exacerbation of bronchial asthma, short wind, nausea, itch, skin rash, small tortoiseshell, hyperhidrosis, mialgiya, nephrite, peripheral hypostases.
System effects of glucocorticosteroids (including Dipropionas beclomethasone) arise at purpose of high doses to a long time. They include: oppression of function of nadpochechni, decrease in mineral density of a bone tissue, a growth inhibition at children and teenagers, glaucoma and a cataract. Reactions of hypersensitivity include: an itch, skin rash, an erythema an eye, persons, lips and a throat also swelled.

Interaction with other medicines:

Blockers of β-adrenergic receptors can weaken action of a formoterol. Foster it is not necessary to appoint along with β-adrenoblockers ((((((((((including eye drops), except for forced cases.
At joint reception of Foster and other β-adrenergic medicines strengthening of side effect of a formoterol is possible.
Joint appointment of Foster and quinidine, Disopyramidum, procaineamide, fenotiazin, antihistaminic drugs (terfenadin), inhibitors of a monoaminooxidase (MAO) and tricyclic antidepressants can extend QTc - an interval and to increase risk of developing of ventricular arrhythmias.
Besides, the levodopa, left thyroxine, oxytocin and alcohol can reduce tolerance of a cardiac muscle to β2-адреномиметикам.
Joint purpose of MAO inhibitors, and also the drugs having similar properties such as furasolidone and Procarbazinum, can cause increase in arterial pressure. There is an increased risk of development of arrhythmias in patients when carrying out the general anesthesia drugs of the halogenated hydrocarbons.
β2-адреномиметиков the hypopotassemia which can amplify at the accompanying treatment by xanthine derivatives, mineral derivatives of glucocorticosteroids or diuretics can result from use. The hypopotassemia can increase predisposition to development of arrhythmias in the patients accepting cardiac glycosides.
Because of the maintenance of a small amount of ethanol manifestation of interaction at the patients with hypersensitivity accepting Disulfiramum or metronidazole is possible.

Contraindications:

Hypersensitivity to drug components, children's age up to 12 years.

With care
Pregnancy, the lactation period, pulmonary tuberculosis, fungal, viral or bacterial infections of a respiratory organs, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrollable hypopotassemia, idiopathic hypertrophic subaortal stenosis, atrioventricular block of the III degree, heavy arterial hypertension, aneurism of any localization or other serious cardiovascular illness (acute myocardial infarction, coronary heart disease, tachyarrhythmia, dekom-pensirovanny chronic heart failure, the extended Q-Tc interval (reception of a formoterol can cause lengthening of QTc-of an interval)).

Pregnancy and lactation
There are no clinical data on Foster's use during pregnancy. During the researches on animals embriotoksichesky or teratogenic action was not vyyaleno.
During pregnancy Foster it is necessary to use only when the advantage of use of drug exceeds potential risk for a fruit. It is recommended to appoint the minimum dose providing effective control of symptoms of bronchial asthma.
There are no data on Foster's penetration into breast milk of women. Foster can be appointed to the feeding women only when the expected therapeutic effect for mother surpasses potential risk for the child.

Overdose:

At overdose there are symptoms, typical for r2-adrenomimetik, caused formoteroly, such as nausea, vomiting, headache, tremor, drowsiness, strong heartbeat, tachycardia, ventricular arrhythmia, lengthening of a QTc-interval, metabolic acidosis, hypopotassemia, hyperglycemia.
At emergence of symptoms of overdose the symptomatic treatment is shown. In hard cases hospitalization. Use of cardioselective beta adrenoblockers at respect for care as use of these means can cause a bronchospasm can be considered. Monitoring of level of potassium in a blood plasma is necessary.
Inhalation of doses of beclomethasone of Dipropionas is higher than recommended can cause temporary oppression of function of bark of adrenal glands. Usually it does not demand acceptance of any emergency measures as in most cases normal function of adrenal glands is recovered within several days. It is recommended to carry out control of level of cortisol in a blood plasma.
At chronic reception of overdoses of beclomethasone of Dipropionas its systemic action can be shown: there can be a significant oppression of bark of adrenal glands up to adrenal crisis. Acute adrenal crisis is shown by the hypoglycemia which is followed by confusion of consciousness and/or spasms. The injury, surgical intervention, an infection or a bystry dose decline of the beclomethasone which is Foster's part belong to situations which can serve as starting factors of acute adrenal crisis. At chronic overdose it is recommended to carry out control of reserve function of bark of adrenal glands.

Storage conditions:

At a temperature + 2-8 °C, in the place protected from the sun, far from heating devices. Not to freeze. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Aerosol for inhalations dosed 100+6 mkg / a dose.
The aluminum barrel with the dosing valve containing 120 doses of drug. On 1 barrel with an inhaler and the instruction place in a cardboard pack.