Foster, aerosol 100 mcg+6 mcg/dose 120 doses

Foster contains beclomethasone dipropionate and formoterol, which have different mechanisms of action and have an additive effect in reducing the frequency of exacerbations of bronchial asthma.

Beclomethasone dipropionate is an inhaled GKS at recommended doses that has anti-inflammatory effects, reduces asthma symptoms, and decreases the frequency of exacerbations, with a lower frequency of side effects than systemic GKS.

Formoterol is a selective β2-adrenoreceptor agonist that causes relaxation of bronchial smooth muscle in patients with reversible airway obstruction. Bronchodilator effect comes on quickly, within 1-3 min after inhalation, and lasts for 12 h after inhalation of a single dose.

The addition of formoterol to beclomethasone dipropionate reduces the severity of bronchial asthma symptoms, improves measures of external respiratory function (ERF) and reduces the frequency of exacerbations of the disease.

In a clinical trial, it was shown that the effect on BPF of the fixed Foster combination was equal to that of the combination of beclomethasone dipropionate and formoterol monotherapy and exceeded that of beclomethasone dipropionate alone.

Pharmacokinetics

Pharmacokinetic parameters for the respective drugs were comparable after administration of beclomethasone dipropionate (BDP) and formoterol as monopreparations and as part of a combination drug.

For beclomethasone dipropionate, the AUC for its active metabolite beclomethasone-17-monopropionate and plasma Cmax values are slightly lower when administered as part of a combination drug, and absorption is faster than for beclomethasone dipropionate monopreparation.

For formoterol, when administered as part of the combination drug, the Cmax in plasma was the same as that of the monodrug, and the systemic effect was slightly higher than that of the monodrug.

There are no data regarding pharmacokinetic or pharmacodynamic interactions between BDP and formoterol: BDP is converted by esterase to the active metabolite beclomethasone-17-monopropionate (B-17 MP).

Inhaled BDP is rapidly absorbed by the lungs; its absorption is preceded by intense conversion of BDP to its active metabolite beclomethasone-17-monopropionate (B-17 MP). Systemic bioavailability (B-17 MP) is 36% due to the lungs and also due to gastrointestinal absorption of the swallowed portion of the inhaled dose. The bioavailability of ingested BDP is negligible; however, the presystemic conversion of BDP to B-17 MP results in 41% of BDP being absorbed by the body as B-17 MP. There is an almost linear increase in systemic action with increasing inhaled dose. The absolute bioavailability after inhalation is approximately 2% and 62% of the nominal dose relative to unchanged BDP u and B-17 MP, respectively.

The binding to plasma proteins is quite high.

Metabolism

BDP is characterized by a very high clearance rate from the great circle of the circulation due to the action of esterase present in most tissues. The main metabolic product of BDP is the active metabolite B-17 MP. Less active metabolites are beclomethasone 21 monopropionate (B-21 MP) and beclomethasone (BON), which are also produced by metabolism, but their role in the systemic effects of BDP is very minor.

The bulk of BDP is excreted in the feces as polar metabolites. Renal excretion of BDP and its metabolites is insignificant. T1/2 of BDP and B-17 MP is 0.5 and 2.7 h, respectively.

Pharmacokinetics in special clinical cases

. Hepatic insufficiency does not alter the pharmacokinetic properties and safety profile of BDP due to the fact that the latter undergoes rapid metabolism to the polar metabolites B-21 MP, BON and B-17 MP under the action of enzymes present in the gastrointestinal tract, blood plasma, lungs and liver.

The pharmacokinetic properties of BDP in patients with renal impairment have not been studied. Taking into account that both BDP and its metabolites are practically not excreted with urine, there is no reason to assume increased systemic action of the drug in patients suffering from renal failure.

Formoterol

Intake and distribution

Inhaled formoterol is absorbed in the lungs and GI tract. The portion of the inhaled dose that is swallowed depends on the type of inhalation device. and inhalation technique. So when using a multi-dose inhaler, it can be up to 90%. Therefore, the swallowed fraction must be taken into account when using the inhalation technique.

No less than 65% of the oral dose of formoterol is absorbed through the gastrointestinal tract, with 70% of this volume undergoing presystemic metabolism. Cmax of unchanged formoterol in plasma is observed within 0.5-1 h after oral administration. The plasma protein binding of formoterol is 61-64%, with an affinity to albumin of 34%. No affinity is observed in the range of therapeutic doses. When administered orally, the T1/2 is 2-3 h. With inhalation of 12-96 mcg formoterol fumarate, the absorption of formoterol is linear.

Metabolism

The metabolism of formoterol is carried out, in particular, by direct conjugation of the phenol hydroxyl group.

Glucuronic acid conjugates are not active. The second significant pathway of formoterol metabolism is O-dimethylation by conjugation at the level of the phenol-2-hydroxyl group. The cytochrome P450 enzymes CYP2D6, CYP2C9, and CYP2C19 are involved in the O-demethylation of formoterol. There is reason to believe that the metabolism of formoterol takes place mainly in the liver. Formoterol does not inhibit CYP450 enzymes at therapeutically significant concentrations.

The total renal excretion of formoterol after inhalation of a single dose via a metered-dose powder inhaler increases linearly in the dose range of 12-96 mcg. The excretion rates of unchanged and total formoterol averaged 8% and 25%, respectively. Based on measurements of plasma concentrations of formoterol after its single inhalation at a dose of 120 mcg in 12 healthy volunteers, the T1/2 was determined to be 10 h. The ratio of (R,R)- and (S,S)-enantiomers of the unchanged drug in renal excretion was 40% and 60%, respectively. The relative ratios of these 2 parameters do not change over the range of doses studied; there is no evidence of accumulation of one enantiomer relative to the other after administration, repeated doses.

In healthy volunteers, after oral administration (40-80 mcg), 6-10% of the dose was detected in the urine as unchanged drug; 8% of the dose was present as glucuronides.

Only 67% of the oral dose of formoterol is excreted by the kidneys (mainly as metabolites); the rest of the dose is excreted through the intestine. Renal clearance of formoterol is 150 ml/min.

Indications

Baseline therapy of bronchial asthma, providing for the prescription of combined therapy (inhaled glucocorticosteroid and β 2 adrenomimetics of long-acting):
– Patients whose symptoms of the disease are not sufficiently controlled by inhaled glucocorticosteroids and β 2 adrenomimetics of short action.
– Patients receiving effective maintenance doses of inhaled glucocorticosteroids and long-acting β 2 adrenomimetics.

Active ingredient

How to take, the dosage

Foster is not intended as an initial treatment for bronchial asthma. Selection of the dose of drugs included in Foster is individual and depending on the severity of the disease. This should be taken into account not only when starting treatment with combination drugs, but also when changing the maintenance dose of the drug. If individual patients require a different combination of doses of the active ingredients than in Foster, β2-adrenomimetics and/or GCS should be prescribed in separate inhalers.

For adults and adolescents over 12 years of age: 1-2 inhalations 2 times/day. Patients should be constantly monitored by a physician for adequate adjustment of the dose of Foster. The dose should be reduced to the lowest dose against which optimal control of bronchial asthma symptoms is maintained. If complete control of bronchial asthma symptoms is achieved at the lowest recommended dose, monotherapy with inhaled GCS may be tried in the next step.

There is no need for a specific dose selection for elderly patients.

There are no data on Foster administration in patients with renal or hepatic impairment.

Inhaler Instructions for Use.

The patient must be taught how to use the inhaler correctly and periodically check inhalation technique.

The first dose of the inhaler should be sprayed in the air before the first use or 3 days or more after you stop using it to make sure it works.

For the second dose: Hold the inhaler upright for about 30 seconds and then repeat Steps 3-5.

The mouthpiece is closed tightly with the protective cap after use.

Phase 3 and 4 should not be rushed. You need to start breathing in as slowly as possible, right before you push down on the valve of the inhaler.

If gas is partially coming out of the top of the inhaler or out of the corner of the patient’s mouth, repeat the sequence from Step 3.

Patients with weak hands are more comfortable holding the inhaler with both hands. Therefore, the top part of the inhaler should be held with the two index fingers and the bottom part with the thumbs.

After inhalation, it is recommended to rinse your mouth with water.

In order to keep the mouthpiece clean, it is recommended that you rinse it with warm water as it becomes soiled.

There is no clinical data available on the use of Foster with a spacer; therefore, the recommended dosage is based on using an inhaler without a spacer with a standard activator.

Please note that dose adjustments may be necessary when using Foster with a spacer.

Interaction

Beta-adrenoreceptor blockers may weaken the effect of formoterol. Foster should not be administered simultaneously with beta-adrenoblockers (including eye drops), except in forced cases.

When coadministering Foster and other beta-adrenergic drugs, the side effects of formoterol may be increased.

The co-administration of Foster and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.
In addition, levodopa, levothyroxine, oxytocin, and alcohol may decrease cardiac muscle tolerance to beta2-adrenomimetics.

The co-administration of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, may cause an increase in BP.
There is an increased risk of arrhythmias in patients undergoing general anesthesia with drugs of halogenated hydrocarbons.

The use of beta2-adrenomimetics may result in hypokalemia, which may increase with concomitant treatment with xanthine derivatives, mineral GCS derivatives, and diuretics. Hypokalemia may increase the predisposition to develop arrhythmias in patients taking cardiac glycosides.

Because of the small amount of ethanol, there may be interactions in hypersensitive patients taking disulfiram or metronidazole.

Special Instructions

If patients have comorbidities such as CHD, myocardial infarction, exacerbation of arterial hypertension, heart rhythm disorders, chronic heart failure, diabetes, prostatic hypertrophy, glaucoma, special caution should be exercised in choosing the Foster dose.

Cautions should be taken when treating patients with prolonged QTc interval (QTc >0.44 sec). Formoterol administration may cause prolongation of the QTc interval. Foster can be used in patients with tachyarrhythmia only if special precautions, such as ECG monitoring, are taken.

Particular precautions should be observed in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve attacks during exacerbations of severe bronchial asthma, since the risk of hypokalemia increases with hypoxia and other conditions when there is an increased possibility of developing hypokalemic effect. In such cases it is recommended to control the content of potassium in serum.

Inhalation of high doses of formoterol may lead to increased blood glucose levels. During the treatment period the blood glucose concentration should be monitored in patients with diabetes mellitus. If anesthesia is planned with preparations of halogenated hydrocarbons, the patient should be warned not to use Foster for 12 hours before anesthesia.

As with other GCSs, the need for and dose of Foster should be reviewed in patients with active or inactive pulmonary tuberculosis, fungal, viral or bacterial respiratory infections.

Because of the risk of exacerbations, treatment with Foster should not be stopped abruptly; the dose of the drug should be reduced gradually and under a physician’s supervision.

When patients are already on this regimen (inhaled or oral GCS), it should be continued without any changes, even if there is improvement in symptoms.

The persistence of bronchial asthma symptoms or the need to increase the Foster dose may indicate a worsening of bronchial asthma and a need to review treatment. Patients are advised to have short-acting beta2-adrenomimetics on hand at all times to manage acute attacks of bronchospasm.

The treatment with Foster should not be prescribed during exacerbations of bronchial asthma.

As with any other inhalation therapy, paradoxical bronchospasm may occur with immediate
increase in wheezing after a dose of the drug. Therefore, therapy with Foster should be discontinued, the therapy should be reconsidered, and alternative therapy should be prescribed if necessary.

Any inhaled GCS can cause systemic effects, especially with long-term use at high doses; however, it should be noted that the likelihood of developing these symptoms is much lower than with oral GCS treatment. Possible systemic effects include inhibition of adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. With this in mind, the dose of inhaled GCS should be titrated to the lowest dose that will maintain effective control.

Chronic use of excessive doses of beclomethasone dipropionate can have systemic effects: significant suppression of the adrenal cortex up to and including adrenal crisis may occur. Adrenal crisis is manifested by anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, hypotension, hypoglycemia, accompanied by confusion and/or seizures. Situations that may serve as triggers for acute adrenal crisis include trauma, surgery, infection, or
rapid reduction in the dose of Foster’s beclomethasone. In chronic overdose, monitoring of adrenal cortical reserve function is recommended.

If there is reason to believe that adrenal function has been impaired on previous systemic GCS therapy, precautions should be taken when transferring patients to treatment with Foster.

The benefits of inhaled therapy generally minimize the need for oral GCS, but patients who discontinue oral GCS therapy may have long-term adrenal insufficient function. Patients who require either a history of high-dose emergent GCS or have been treated with high-dose, long-term inhaled GCS may also be at risk.

Additional prescribing of GCS should be considered during stress or surgery.

Patients should be instructed to rinse their mouth with water after inhaling maintenance doses to prevent the risk of oral and pharyngeal candidiasis.

The cylinder is pressurized: do not expose to heat, do not pierce, do not throw into fire, even empty. Use within 3 months of use.

Contraindications

Hypersensitivity to the components of Foster, children under 12 years of age.
With caution:
Pregnancy, lactation, pulmonary tuberculosis, fungal, viral or bacterial respiratory infections, thyrotoxicosis, pheochromocytoma, diabetes, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, atrioventricular block of degree III, Severe arterial hypertension, aneurysm of any localization or other severe cardiovascular diseases (acute myocardial infarction, coronary heart disease, tachyarrhythmia, decompensated chronic heart failure, prolonged Q-Ts interval (formoterol administration may cause prolongation of QTs interval).

Side effects

Foster contains beclomethasone dipropionate and formoterol fumarate, and therefore it is to be expected that it may cause side effects characteristic of these components. There is no evidence that their concomitant use causes additional side effects.

The side effects associated with the use of beclomethasone dipropionate and formoterol as a fixed combination (Foster) are as follows.

CNS side effects: often – headache.

Respiratory system disorders: frequent – voice hoarseness; less frequent – rhinitis, dysphonia, cough, mild throat irritation, bronchospasm.

Cardiovascular system: less frequently – palpitations, prolongation of the QT interval, ECG changes.

Muscular system disorders: tremor, muscle cramps.

Hematopoietic system: granulocytopenia, increased number of platelets.

Digestive system disorders: dry mouth, burning sensation in the lips, dysphagia, dyspepsia, diarrhea.

Immune system disorders: allergic dermatitis; increase in C-reactive protein.

Metabolic disorders: hypokalemia.

Infections: pharyngitis, influenza, candidiasis of the mucous membrane of the mouth, pharynx and esophagus, vaginal candidiasis, gastroenteritis, sinusitis.

The most common side effects associated with formoterol administration include those typical of beta2-adrenomimetics, such as hypokalemia, headache, tremor, palpitations, coughing, muscle cramps, and prolongation of the QTc interval.

Side effects common with beclomethasone dipropionate: candidiasis of the mucous membranes of the mouth and throat, irritation in the throat.

Like other inhaled drugs, Foster can cause paradoxical bronchospasm.

Other side effects common to formoterol are: Thrombocytopenia, angioneurotic edema, hyperglycemia, increased blood levels of insulin, free fatty acids, glycerol and ketone derivatives, sleep disturbances, hallucinations, fatigue, restlessness, altered taste sensation (dysgeusia), tachycardia tachyarrhythmia, ventricular extrasystoles, angina pectoris, atrial fibrillation, arterial hypertension, arterial hypotension, exacerbation of bronchial asthma, shortness of breath, nausea, itching, skin rash, urticaria, hyperhidrosis, myalgia, nephritis, peripheral edema.

The systemic effects of GKS (including beclomethasone dipropionate) occur when high doses are prescribed for a long time. They include: suppression of adrenal function, decreased bone mineral density, growth retardation in children and adolescents, glaucoma and cataracts.

Sensitivity reactions include: itching, skin rash, erythema and swelling of the eyes, face, lips and throat.

Overdose

Symptoms: in overdose, symptoms typical of beta2-adrenomimetics due to formoterol occur, such as nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmia, prolongation of QTc interval, metabolic acidosis, hypokalemia, hyperglycemia.

Treatment: symptomatic treatment. In severe cases, hospitalization. The use of cardioselective beta-adrenoblockers may be considered, with caution, since the use of these agents may cause bronchospasm. Plasma potassium levels should be monitored.

Inhalation of doses of beclomethasone dipropionate above the recommended doses may cause temporary inhibition of adrenal cortical function. This usually does not require any emergency action because in most cases normal adrenal function is restored within a few days. Monitoring of plasma cortisol levels is recommended.

In chronic use of excessive doses of beclomethasone dipropionate, its systemic effects may become apparent: significant suppression of the adrenal cortex up to and including adrenal crisis may occur. Acute adrenal crisis is manifested by hypoglycemia accompanied by confusion and/or seizures. Situations that may serve as triggers for acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of Foster’s beclomethasone. In chronic overdose, monitoring of adrenal cortical reserve function is recommended.

Pregnancy use

There are no clinical data on the use of Foster during pregnancy. No embryotoxic or teratogenic effects have been identified in animal studies.

In pregnancy Foster should be used only in cases when the benefit of using the drug exceeds the potential risk to the fetus. It is recommended to prescribe the minimum dose that provides effective control of bronchial asthma symptoms.

There are no data on penetration of Foster into the breast milk of women. Foster may be administered to breastfeeding women only in cases where the expected therapeutic effect for the mother outweighs the potential risk to the baby.