Foster^® (Aerosol) Instructions for Use

ATC Code

R03AK08 (Formoterol and Beclomethasone)

Active Substances

Beclometasone (Rec.INN registered by WHO)

Formoterol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Combined bronchodilator drug – selective beta₂-adrenomimetic + topical glucocorticosteroid

Pharmacotherapeutic Group

Combined bronchodilator agent (selective beta₂-adrenomimetic + topical glucocorticosteroid)

Pharmacological Action

The drug Foster^® contains beclometasone dipropionate and formoterol – two active substances with different mechanisms of action that exhibit an additive effect in reducing the frequency of exacerbations of bronchial asthma.

When inhaled at recommended doses, beclometasone dipropionate exerts a characteristic anti-inflammatory effect on the airways and lungs typical of glucocorticosteroids, reduces the severity of bronchial asthma symptoms and the frequency of its exacerbations, but has fewer side effects than systemic glucocorticosteroids.

Formoterol is a selective agonist of β₂-adrenergic receptors, causing relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilatory effect after inhalation of a single dose of formoterol occurs rapidly (within 1-3 minutes) and lasts for 12 hours.

Clinical efficacy and safety

Bronchial asthma

Clinical efficacy of the drug Foster^® when used as regular therapy

The addition of formoterol to beclometasone dipropionate reduces the severity of bronchial asthma symptoms, improves lung function parameters and reduces the frequency of bronchial asthma exacerbations.

A 24-week clinical study showed that the effect of the drug Foster^® on lung function parameters corresponds to that of the combination of monodrugs beclometasone dipropionate and formoterol and exceeds the effect of beclometasone dipropionate alone on lung function parameters.

Clinical efficacy of the drug Foster^® when used as regular and reliever therapy (Maintenance And Reliever Therapy – MART)

In a clinical study conducted in adult patients with uncontrolled moderate to severe bronchial asthma, the efficacy of Foster^®, taken as regular therapy (1 inhalation 2 times/day) and as needed for relief of asthma symptoms (up to 8 inhalations/day in total), was compared with the efficacy of Foster^®, taken as regular therapy (1 inhalation 2 times/day) plus the use of salbutamol as needed. It was shown that Foster^®, when used for regular therapy and for relief of bronchial asthma symptoms, significantly increased the time to the first severe exacerbation of bronchial asthma (defined as a worsening of the severity of bronchial asthma leading to hospitalization or treatment in an intensive care unit, or the need for oral glucocorticosteroids for more than 3 days), compared with the use of Foster^® as regular therapy plus the use of salbutamol as needed.

The frequency of severe bronchial asthma exacerbation per patient/year was significantly and statistically lower in the group of patients receiving Foster^® as regular therapy and for relief of bronchial asthma symptoms, compared with the group of patients taking Foster^® as regular therapy and salbutamol for bronchial asthma symptoms (0.1476 versus 0.2239, respectively). Patients in the group using Foster^® as regular therapy and for relief of bronchial asthma symptoms achieved more significant clinical improvement in asthma symptom control. Both groups showed an equal reduction in the average number of inhalations of reliever medications per day and the percentage of patients taking reliever medications for bronchial asthma symptoms.

In another clinical study conducted in patients with bronchial asthma, using methacholine bronchospasm provocation, it was shown that a single dose of Foster^® at a dose of 100+6 mcg provided a rapid bronchodilatory effect and rapid relief of dyspnea, similar to that of salbutamol at a dose of 200 mcg.

Chronic obstructive pulmonary disease (COPD)

In two 48-week clinical studies conducted in patients with severe COPD (30%< FEV₁ % <50%), the effects on lung function and the frequency of exacerbations (defined as conditions requiring a course of oral glucocorticosteroids and/or a course of antibiotics and/or hospitalization) were evaluated.

One pivotal clinical study showed a significant improvement in lung function compared with formoterol after 12 weeks of treatment (primary endpoint: change in pre-dose FEV₁; adjusted mean difference between Foster^® and formoterol – 69 ml), as well as an improvement in lung function compared with formoterol at each clinic visit throughout the treatment period (48 weeks). The study demonstrated that over 48 weeks of treatment in 1199 patients with severe COPD, the mean number of exacerbations per patient per year (exacerbation rate, primary composite efficacy endpoint) was statistically significantly reduced with Foster^® compared with formoterol treatment (adjusted mean rate 0.80 compared with 1.12 in the formoterol group, adjusted ratio 0.72, p <0.001). In addition, Foster^® statistically significantly increased the time to first exacerbation compared with formoterol. The superiority of Foster^® over formoterol was also confirmed regarding the exacerbation rate in subgroups of patients taking or not taking tiotropium bromide as a concomitant medication.

Another pivotal clinical study, a randomized study conducted in 3 parallel groups of patients involving 718 patients, confirmed the superiority of Foster^® compared with formoterol treatment in terms of change in pre-dose FEV₁ at the end of treatment (after 48 weeks) and demonstrated the non-inferior efficacy of Foster^® compared with the fixed combination of budesonide and formoterol for the same parameter.

Pharmacokinetics

The systemic exposure of beclometasone dipropionate and formoterol in the fixed combination of the drug Foster^® was compared with that of the monodrugs beclometasone dipropionate and formoterol.

In healthy volunteers taking Foster^® as a single dose (4 doses of 100+6 mcg) or a single dose of beclometasone dipropionate with chlorofluorocarbon (CFC) propellant (4 doses of 250 mcg) and Formoterol with hydrofluoroalkane (HFA) propellant (4 doses of 6 mcg), the AUC of the main active metabolite of beclometasone dipropionate – beclometasone-17-monopropionate (B-17-MP) and its plasma C_max when using Foster^® were 35% and 19% lower, respectively, than when using the beclometasone dipropionate dosage form with CFC propellant and non-extrafine aerosol particle size distribution, and, conversely, its absorption rate was higher (0.5 h versus 2 h) when using Foster^® compared with using beclometasone dipropionate alone with CFC propellant in the dosage form with non-extrafine aerosol particle size distribution.

After administration of the fixed combination (Foster^®) or the combination of monodrugs beclometasone dipropionate and formoterol (from two separate metered dose inhalers), the plasma C_max of formoterol were similar, and its systemic exposure was slightly higher after administration of Foster^® than when using two separate inhalers of beclometasone dipropionate and formoterol in a free combination.

No data were obtained confirming the presence of pharmacokinetic or pharmacodynamic (systemic) interaction between beclometasone dipropionate and formoterol.

In healthy volunteers, the use of the AeroChamber Plus^® spacer device compared to the use of a standard actuator increased the lung deposition of the active metabolite B-17-MP and formoterol by 41% and 45%, respectively. The total systemic exposure of formoterol did not change, the total systemic exposure of B-17-MP decreased by 10%, and the total systemic exposure of unchanged beclometasone dipropionate increased.

A study on the deposition of the drug components in the airways, conducted in stable COPD patients, healthy volunteers and patients with bronchial asthma, showed that on average 33% of the nominal dose is deposited in the lungs of COPD patients compared to 34% in healthy individuals and 31% in patients with bronchial asthma.

Within 24 hours after inhalation, the plasma exposures of B-17-MP and formoterol were comparable in all 3 groups. The total exposure of beclometasone dipropionate was greater in COPD patients than in patients with bronchial asthma and healthy volunteers.

Beclometasone dipropionate

Absorption, distribution and metabolism

Beclometasone dipropionate is a prodrug with low affinity for glucocorticoid receptors, which is converted by esterases present in most tissues into its active metabolite B-17-MP, which has a more pronounced anti-inflammatory effect than the prodrug – beclometasone dipropionate.

After inhalation, beclometasone dipropionate is rapidly absorbed from the lungs; its absorption is preceded by intensive conversion of beclometasone dipropionate into its active metabolite B-17-MP. The systemic bioavailability of B-17-MP consists of its absorption from the lungs (36%) and from the gastrointestinal tract (from the swallowed portion of the inhalation dose). The bioavailability of the swallowed portion of the beclometasone dipropionate dose is negligible; however, presystemic conversion of beclometasone dipropionate to B-17-MP results in 41% of the swallowed dose being absorbed as the active metabolite B-17-MP. With increasing inhalation dose, an almost linear increase in the systemic exposure of B-17-MP is observed. The absolute bioavailability after inhalation for unchanged beclometasone dipropionate and B-17-MP is about 2% and 62% of the nominal dose, respectively.

After IV administration, beclometasone dipropionate and its active metabolite B-17-MP are characterized by high plasma clearance (150 L/h and 120 L/h, respectively), a small V_d at steady-state concentration for beclometasone dipropionate (20 L) and a large V_d for its active metabolite B-17-MP (42 L). The main metabolite of beclometasone dipropionate is its active metabolite B-17-MP. Less active metabolites of beclometasone dipropionate are beclometasone-21-monopropionate (B-21-MP) and beclomethasone, but their role in the systemic action of beclometasone dipropionate is very insignificant.

Binding to plasma proteins is moderately high.

Elimination

The main part of beclometasone dipropionate is excreted through the intestine with feces in the form of polar metabolites. Renal excretion of beclometasone dipropionate and its metabolites is negligible. T_1/2 of beclometasone dipropionate and B-17-MP is 0.5 h and 2.7 h, respectively.

Pharmacokinetics in special patient groups

The pharmacokinetics of beclometasone dipropionate in patients with renal or hepatic impairment has not been studied. However, in hepatic impairment, no change in the pharmacokinetics and safety profile of beclometasone dipropionate is expected, since it undergoes very rapid metabolism under the influence of esterase enzymes present in the fluid contents of the small intestine, blood serum, lungs and liver, with the formation of more polar products: B-21-MP, B-17-MP and beclomethasone.

No increase in systemic exposure of beclometasone dipropionate and its metabolites is expected in patients with renal impairment, as they are practically not excreted by the kidneys.

Formoterol

Absorption and distribution

After inhalation, formoterol is absorbed from both the lungs and the gastrointestinal tract. The swallowed portion of the inhalation dose is absorbed from the gastrointestinal tract, which can range from 60% to 90% of the inhalation dose depending on the type of inhalation device and inhalation technique, with at least 65% of the swallowed portion of the dose being absorbed from the gastrointestinal tract. After oral administration, the plasma C_max of unchanged formoterol is reached within 0.5-1 h. The binding of formoterol to plasma proteins is 61-64%, with binding to albumin being 34%. No saturation of formoterol binding to plasma proteins was observed in the range of plasma concentrations achieved at therapeutic doses. After oral administration, T_1/2 is 2-3 h. The absorption of formoterol in the dose range of formoterol fumarate from 12 mcg to 96 mcg is linear.

Metabolism

Formoterol is intensively metabolized, mainly in the liver, the main pathway of its metabolism is conjugation with glucuronic acid to form an inactive metabolite. The second important metabolic pathway is O-demethylation followed by conjugation. The O-demethylation of formoterol involves the CYP2D6, CYP2C19 and CYP2C9 isoenzymes. Formoterol at therapeutically significant concentrations does not inhibit the CYP450 system isoenzymes.

Elimination

After a single inhalation of formoterol in doses from 12 to 96 mcg from a powder inhaler, a linear increase in the total renal excretion of formoterol is observed. On average, 8% and 25% of the dose is excreted by the kidneys as unchanged formoterol and the sum of all its metabolites, respectively. After inhalation of a single dose of 120 mcg, the T_1/2 from plasma was 10 h. The right- and left-handed enantiomers of unchanged formoterol excreted by the kidneys were approximately 40% and 60%, respectively. The relative proportion of the two enantiomers remained constant throughout the studied dose range, and after repeated doses, no relative accumulation of one enantiomer compared to the other enantiomer was observed.

After oral administration of formoterol (40-80 mcg) to healthy volunteers, 6-10% of the dose was found in the urine as unchanged formoterol and up to 8% of the dose was found in the urine as glucuronides.

In total, 67% of the formoterol dose when taken orally is excreted by the kidneys (mainly as metabolites), and the remainder is excreted through the intestine with feces. The renal clearance of formoterol is 150 ml/min.

Pharmacokinetics in special patient groups

Hepatic/renal impairment: the pharmacokinetics of formoterol in patients with hepatic or renal impairment has not been studied, however, since formoterol is predominantly eliminated by hepatic metabolism, an increase in its systemic exposure can be expected in patients with severe liver cirrhosis.

Indications

The drug Foster^® is indicated for use in adults aged 18 years and older.

Basic therapy of bronchial asthma, involving the use of combination therapy (inhaled glucocorticosteroid + long-acting beta₂-adrenergic agonist):

• In patients whose disease symptoms are not sufficiently controlled by the use of inhaled glucocorticosteroids and fast-acting beta₂-adrenergic agonists;
• In patients already receiving effective maintenance doses of inhaled glucocorticosteroids and long-acting beta₂-adrenergic agonists.

Chronic obstructive pulmonary disease (COPD)

• Treatment of bronchial obstruction in patients with severe COPD (FEV₁ <50% of its predicted normal value) and a history of repeated exacerbations, who, despite conventional bronchodilator therapy, continue to have significant symptoms of this disease.

ICD codes

Dosage Regimen

Aerosol

The drug Foster^® is intended for inhalation use.

Bronchial asthma

The drug Foster^® is not intended for the initial treatment of bronchial asthma. The selection of doses of the active substances included in the drug Foster^® occurs individually depending on the severity of the disease. This must be taken into account not only when starting treatment with combination drugs, but also when changing their dose.

In the event that individual patients require a different combination of doses of active substances than that in the drug Foster^®, they should take the appropriate doses of beta₂-adrenergic agonists and/or glucocorticosteroids in separate inhalers. Beclometasone dipropionate in the drug Foster^® is characterized by an extrafine aerosol particle distribution, which leads to a more pronounced effect than beclometasone dipropionate in the dosage form with non-extrafine aerosol particle size distribution (thus, 100 mcg of beclometasone dipropionate with extrafine aerosol particle size distribution in the drug Foster^® is equivalent to 250 mcg of beclometasone dipropionate in the dosage form with non-extrafine aerosol particle size distribution). Therefore, the total daily dose of beclometasone dipropionate used in the drug Foster^® should be lower than the total dose of beclometasone dipropionate used in the dosage form with non-extrafine aerosol particle distribution.

This should be taken into account when a patient is switched from beclometasone dipropionate in the dosage form with non-extrafine aerosol particle size distribution to the drug Foster^®: the dose of beclometasone dipropionate in the drug Foster^® should be lower, and its selection should be carried out depending on the individual needs of the patients.

There are two approaches for the treatment of bronchial asthma with the drug Foster^®

• Regular therapy – the drug Foster^® is used as regular therapy with the additional use of a fast-acting bronchodilator as needed;
• Regular therapy and use as needed for relief of bronchial asthma symptoms – the drug Foster^® is used as regular therapy and in response to the development of bronchial asthma symptoms as needed.

Regular therapy

Patients should be advised to have a separate rapid-acting bronchodilator inhaler with them, which they can use to relieve symptoms of bronchial asthma at any time.

Adults (18 years and older)– 1 or 2 inhalations 2 times/day. The maximum daily dose is 4 inhalations.

Regular therapy and as-needed use for relief of bronchial asthma symptoms

Patients take their constant daily dose of Foster^® and additionally take Foster^® as needed to relieve symptoms of bronchial asthma. Patients should be advised to always have Foster^® with them for relief of bronchial asthma symptoms.

The need for using Foster^® as regular therapy and as needed for relief of bronchial asthma symptoms should be considered especially:

• In patients with incompletely controlled bronchial asthma who require medications for relief of asthma symptoms;
• In patients with a past exacerbation of bronchial asthma that required medical intervention.

Patients who frequently use a large number of as-needed inhalations of Foster^® for relief of bronchial asthma symptoms require careful monitoring for the development of dose-dependent adverse effects.

Adults (18 years and older) – the recommended dose for regular therapy is 1 inhalation 2 times/day (1 inhalation in the morning and 1 inhalation in the evening).

In response to the development of bronchial asthma symptoms, patients may take one additional inhalation of Foster^®. If symptoms persist after a few minutes, a second additional inhalation of Foster^® should be taken.

The maximum daily dose is 8 inhalations of Foster^®.

Patients who require frequent use of inhalations for relief of bronchial asthma symptoms should be strongly advised to consult a doctor. The severity of bronchial asthma in such patients should be reassessed and their regular therapy should be reviewed.

Children and adolescents under 18 years

The safety and efficacy of Foster^® in children and adolescents under 18 years of age have not been sufficiently studied, therefore it is not possible to provide recommendations on the dosing regimen for pediatric and adolescent patients.

The condition of patients should be regularly reassessed by a doctor, as the dosing regimen of Foster^® is maintained at an optimal level and is changed only on the recommendation of a doctor. The dose should be titrated to the minimum value at which optimal control of bronchial asthma symptoms is maintained. When control of bronchial asthma symptoms is achieved, the issue of gradually reducing the dose of Foster^® can be considered. When reducing the dose, regular examination of the patient is important. The lowest effective dose of the drug should be used. When complete control of bronchial asthma symptoms is achieved with the minimum recommended dose of the drug, at the next stage an attempt can be made to switch the patient to taking a single inhaled corticosteroid.

The patient should be warned about the need for daily use of Foster^®, even in the absence of bronchial asthma symptoms.

COPD

Adults (18 years and older) – 2 inhalations 2 times/day.

Special patient groups

In elderly patients, no special dose adjustment of the drug is required.

In patients with renal or hepatic impairment, there are no data on the use of Foster^® (see the “Pharmacokinetics” section).

Instructions for use of the inhaler

A doctor or other healthcare professional should instruct the patient on the correct use of the inhaler and periodically check the inhalation technique. Correct use of the metered dose inhaler is a mandatory condition for successful treatment. The patient should be advised to carefully read the package leaflet and follow the recommendations contained therein.

The Foster^® inhaler has a dose counter on the back of the spray device (for the presentation containing 120 doses) or a dose indicator (for the presentation containing 180 doses), which show how many inhalation doses remain. For the presentation containing 120 doses, each time the canister is pressed and the aerosol is sprayed, the dose counter reading decreases by one unit. For the presentation containing 180 doses, each time the canister is pressed and the aerosol is sprayed, the indicator rotates slightly, with the number of remaining inhalation doses displayed in intervals of 20 doses.

The inhaler should not be dropped, as this may lead to an erroneous decrease in the reading of the remaining inhalation doses on the dose counter or dose indicator.

Checking (testing) the inhaler

Before first use of the inhaler or if it has not been used for 14 days or more, 1 dose of aerosol should be released into the air to ensure that the inhaler is working correctly.

After testing for the first time, the inhaler containing 120 doses should show the number 120 on the counter.

After testing for the first time, the inhaler containing 180 doses should show the number 180 on the indicator.

Inhalation procedure

Whenever possible, inhalations should be performed in a “standing” or “sitting” position.

1. The patient should remove the protective cap from the inhaler mouthpiece and check its cleanliness: the mouthpiece should be clean, free of dust, and free of dirt or other foreign objects.
2. The patient should exhale as slowly and deeply as possible.
3. The patient should hold the canister vertically, so that the bottom of the inhaler is pointing upwards, and place the mouthpiece between the lips, without biting it with the teeth.
4. The patient should take the slowest and deepest possible breath through the mouth. After starting to inhale, press down on the bottom of the canister to release 1 dose of aerosol, while continuing to take a deep breath.
5. After inhalation, hold your breath for as long as possible, then remove the mouthpiece from the mouth and exhale slowly. Do not exhale into the inhaler.

To take an additional inhalation, hold the inhaler in a vertical position for approximately 30 seconds and then repeat steps 2 through 5.

Attention do not perform steps 2-5 too quickly.

After using the inhaler, the mouthpiece should be tightly closed with the protective cap and the dose counter or indicator should be checked.

It is recommended to purchase a new inhaler when the dose counter or indicator shows the number 20. When the dose counter or indicator shows 0, the inhaler should be discontinued, as any amount of aerosol remaining in the device may be insufficient to provide a full dose.

If during inhalation the aerosol partially escapes from the top of the inhaler or from the corners of the patient’s mouth, the inhalation procedure should be repeated, starting from step 2.

Patients with weak hands may find it easier to hold the inhaler with both hands. Therefore, the bottom of the canister should be held with two index fingers, and the base of the inhaler should be held with two thumbs.

After inhalation, it is necessary to rinse the mouth and throat with water or brush the teeth (see the “Special Precautions” section).

Cleaning the inhaler

For regular cleaning of the inhaler, patients should remove the protective cap from the mouthpiece and wipe the mouthpiece inside and out with a dry cloth. The inhaler should be cleaned once a week.

Patients should not remove the canister from the inhaler and should not use water or other liquids to clean the mouthpiece.

Patients who have difficulty synchronizing aerosol release and inhalation may use the AeroChamber Plus^® spacer. The attending physician, pharmacist, or nurse should instruct such patients on the correct use and care of the inhaler and spacer device and check their inhalation technique to ensure optimal delivery of the inhaled drug to the lungs. When using the AeroChamber Plus^® spacer device, optimal inhalation technique is achieved by taking one continuous, slow, and deep breath through the spacer without a pause between pressing the inhaler and starting inhalation.

Adverse Reactions

Foster^® contains beclometasone dipropionate and formoterol fumarate, and therefore it can be expected to cause adverse effects characteristic of these components. There are no data indicating that their simultaneous use causes additional adverse effects.

Adverse effects that have been associated with beclometasone dipropionate and formoterol, used as a fixed combination in Foster^® and when used as separate drugs, are presented below and grouped by system-organ class. Definition of frequency categories of adverse effects: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000) and very rare (<1/10000), frequency unknown - based on available data it is not possible to determine the frequency of occurrence of the adverse effect.

Infections and infestations: common – pharyngitis, oral candidiasis, pneumonia^*(in patients with COPD); uncommon – influenza, fungal infections of the mouth, candidiasis of the pharynx and esophagus, vaginal candidiasis, gastroenteritis, sinusitis, rhinitis.

Blood and lymphatic system disorders uncommon – granulocytopenia; very rare – thrombocytopenia.

Immune system disorders uncommon – allergic dermatitis; very rare – hypersensitivity reactions, including erythema, swelling of the lips, face, eyes and pharynx.

Endocrine system disorders very rare – adrenal suppression.

Metabolism and nutrition disorders uncommon – hypokalaemia, hyperglycaemia.

Psychiatric disorders: uncommon – agitation; very rare – psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioral disturbances (mainly in children).

Nervous system disorders common – headache; uncommon – tremor, dizziness.

Eye disorders very rare – glaucoma, cataract; frequency unknown – blurred vision (see the “Special Precautions” section).

Ear and labyrinth disorders: uncommon – tubo-otitis.

Cardiac disorders uncommon – palpitations, QT_c prolongation, ECG changes, tachycardia, tachyarrhythmia, atrial fibrillation^*; rare – ventricular extrasystoles, angina pectoris.

Vascular disorders: uncommon – hyperaemia, flushing.

Respiratory, thoracic and mediastinal disorders common – dysphonia; uncommon – cough, productive cough, pharyngeal pain, reduced effectiveness or ineffectiveness of drugs and measures previously usually helping the patient during an attack of bronchospasm; rare – paradoxical bronchospasm; very rare – dyspnoea, exacerbation of bronchial asthma.

Gastrointestinal disorders uncommon – diarrhoea, dry mouth, dyspepsia, dysphagia, burning sensation in the lips, nausea, dysgeusia (taste disturbance).

Skin and subcutaneous tissue disorders uncommon – pruritus, rash, hyperhidrosis, urticaria; rare – angioedema.

Musculoskeletal and connective tissue disorders: uncommon – muscle spasms, myalgia; very rare – growth retardation in children and adolescents.

Renal and urinary disorders rare – nephritis.

General disorders and administration site conditions very rare – peripheral oedema; frequency unknown – fatigue.

Investigations uncommon – increased C-reactive protein, increased platelet count in peripheral blood, increased concentration of free fatty acids, insulin, ketone bodies, glycerol in blood, decreased blood cortisol concentration^*; rare – increased blood pressure, decreased blood pressure; very rare – decreased bone density.

^* One related non-serious case of pneumonia was reported in one patient receiving Foster^® in a pivotal clinical trial conducted in patients with COPD. Other adverse reactions observed with the use of Foster^® in clinical studies conducted in patients with COPD were decreased blood cortisol concentration and atrial fibrillation.

Description of selected adverse reactions

As with any other inhalation therapy, paradoxical bronchospasm may occur (see the “Special Precautions” section).

Adverse reactions usually associated with the use of formoterol hypokalaemia, headache, tremor, palpitations, cough, muscle spasms and QT_c prolongation.

Adverse reactions usually associated with the use of beclometasone dipropionate fungal infections of the oral mucosa, oral candidiasis, dysphonia, pharyngeal pain.

The possibility of developing dysphonia and candidiasis can be reduced by rinsing the mouth and throat with water or brushing the teeth after using the drug. Symptomatic candidiasis can be treated with local antifungal therapy while continuing treatment with Foster^®.

When using inhaled corticosteroids, including beclometasone dipropionate, systemic effects of corticosteroids may occur, especially when using inhaled corticosteroids in high doses for a long time. They may manifest as adrenal suppression, decreased bone mineral density, growth retardation in children and adolescents, development of cataract and glaucoma (see the “Special Precautions” section).

Hypersensitivity reactions are also possible, including rash, pruritus with urticaria, erythema or swelling of the eyes, face, lips and throat (pharynx and larynx).

Contraindications

• Hypersensitivity to the active substances and excipients of the drug;
• Children under 18 years of age.

With caution

• During pregnancy and childbirth;
• During breastfeeding;
• In pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory tract;
• In thyrotoxicosis;
• In phaeochromocytoma; in diabetes mellitus;
• In uncontrolled hypokalaemia (since treatment with beta₂-adrenergic agonists itself can cause potentially dangerous hypokalaemia, especially when taken concomitantly with drugs that can cause hypokalaemia, such as xanthine derivatives, corticosteroids and diuretics, and also because in patients with severe bronchial asthma, hypoxia may potentiate effects associated with hypokalaemia – see the “Special Precautions” section);
• In idiopathic hypertrophic subaortic stenosis;
• In hypertrophic obstructive cardiomyopathy;
• In cardiac arrhythmias, especially third-degree AV block and tachyarrhythmia;
• In severe arterial hypertension;
• In the presence of an aneurysm of any location;
• In the presence of other severe cardiovascular diseases (acute myocardial infarction, chronic coronary artery disease, chronic heart failure, occlusive vascular lesions, especially atherosclerotic);
• In congenital or drug-induced prolongation of the QT_c interval >0.44 sec) (taking formoterol may cause QT_c prolongation).

Use in Pregnancy and Lactation

There is no experience with the use of the propellant HFA-134a (norflurane) or evidence of its safety during pregnancy and breastfeeding in humans. However, studies on the effect of HFA-134a on reproductive function and embryofetal development conducted in animals did not reveal any clinically significant effects.

Pregnancy

There are no clinical data on the use of Foster^® during pregnancy. Studies conducted in animals using the combination of beclometasone dipropionate and formoterol showed reproductive toxicity only after their high systemic exposure. Due to the tocolytic effect of beta₂-adrenergic drugs, particular caution should be exercised during childbirth. Formoterol should not be recommended for use during pregnancy and, especially, at the end of pregnancy or during childbirth. If possible, another (safer during pregnancy) therapy should be used.

During pregnancy, Foster^® should be used only in cases where the expected therapeutic benefit for the mother outweighs the potential risk to the fetus. It is recommended to use the minimum dose that provides effective control of bronchial asthma or COPD symptoms.

Breastfeeding period

Clinical data on the use of Foster^® during breastfeeding in humans are insufficient. Although there are no data from experimental studies in animals, it can be assumed that beclometasone dipropionate, like other corticosteroids, passes into breast milk. It is not known whether Formoterol is excreted in human breast milk, but in animals it was excreted in breast milk.

Foster^® can be used in breastfeeding women only in cases where the expected therapeutic benefit for the mother outweighs the potential risk for the breastfed infant.

Use in Hepatic Impairment

There are no data on the use of Foster^® in patients with hepatic impairment.

Use in Renal Impairment

There are no data on the use of Foster^® in patients with renal impairment.

Pediatric Use

The use of the drug is contraindicated in children under 18 years of age.

Geriatric Use

No special dose adjustment of the drug is required for elderly patients.

Special Precautions

If patients have such concomitant diseases as cardiac arrhythmias, especially third-degree AV block and tachyarrhythmia, idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart diseases: acute myocardial infarction, chronic coronary artery disease, chronic heart failure, occlusive vascular lesions, especially atherosclerotic, aneurysm, arterial hypertension, as well as prostatic hyperplasia, glaucoma, special caution should be exercised when using Foster^®, and such patients may require monitoring of their condition.

Treatment of patients with known or suspected prolongation of the QT_c interval, either congenital or drug-induced (QT_c>0.44 sec) should be carried out with caution, as the use of formoterol may cause QT_c prolongation.

Caution is also required when Foster^® is used in patients with thyrotoxicosis, diabetes mellitus, phaeochromocytoma and with uncorrected hypokalaemia. Treatment with beta₂-adrenergic agonists may cause potentially severe hypokalaemia. Particular caution is recommended in patients with severe bronchial asthma, as adverse effects associated with hypokalaemia may be potentiated by hypoxia. Hypokalaemia may also be potentiated by concomitant treatment with other drugs that can cause hypokalaemia, such as xanthine derivatives, mineralocorticoids, corticosteroids and diuretics (see the “Drug Interactions” section).

Special caution should be exercised in patients with unstable bronchial asthma using rapid-acting bronchodilators to relieve asthma symptoms. In such cases, monitoring of serum potassium levels is recommended.

Inhalation of formoterol in high doses may lead to increased blood glucose concentrations. In patients with diabetes mellitus, blood glucose levels should be monitored during treatment with Foster^®.

If general anesthesia with halogenated hydrocarbons is planned, the patient should be advised not to use Foster^® inhalations for at least 12 hours before the start of anesthesia (due to the risk of cardiac arrhythmias).

As with other drugs containing inhaled corticosteroids (ICS), the necessity and dose of Foster^® should be re-evaluated in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral, or bacterial respiratory infections.

Due to the danger of exacerbation of bronchial asthma or COPD, treatment with Foster^® should not be abruptly discontinued; the dose should be reduced gradually and under medical supervision.

If the patient considers the treatment ineffective, they should consult a doctor. An increased need for bronchodilators to relieve asthma symptoms indicates a worsening of the disease and requires re-evaluation of asthma treatment. Sudden and progressive worsening of asthma or COPD symptom control is potentially life-threatening and requires urgent medical examination of the patient. The need to increase the dose of corticosteroids (either inhaled or oral) should be considered, and if an infection is suspected, the need for antibiotics should be considered.

Treatment with Foster^® should not be initiated during an asthma exacerbation, or if the patient experiences a significant worsening of its severity or an acute deterioration of asthma. During treatment with Foster^®, serious asthma-related adverse events and complications may occur. If asthma symptoms cannot be controlled or worsen after starting treatment with Foster^®, patients are advised to continue treatment but consult a doctor.

As with any other inhalation therapy, paradoxical bronchospasm may occur with immediate increased wheezing and shortness of breath after inhalation of a dose of the drug. Paradoxical bronchospasm should be relieved immediately with rapid-acting inhaled bronchodilators. Therapy with Foster^® should be discontinued, the treatment strategy should be re-evaluated, and, if necessary, the patient should be switched to alternative therapy.

Foster^® should not be used for the initial treatment of bronchial asthma.

For the treatment of an acute asthma attack, patients should be advised to always carry a rapid-acting bronchodilator: either Foster^® (for patients using this drug as regular therapy and as needed for symptom relief), or a separate rapid-acting bronchodilator (for patients using Foster^® only as regular therapy).

The patient should be warned about the need to take Foster^® daily according to the doctor’s recommendations, even in the absence of asthma symptoms.

Inhalations of Foster^® for the relief of asthma symptoms should be used in response to the development of asthmatic symptoms, but they are not intended for regular prophylactic use, for example, before physical exertion. For this purpose, the possibility of using a separate rapid-acting bronchodilator should be considered.

Once control of asthma symptoms is achieved, a gradual reduction in the dose of Foster^® can be considered. When reducing the dose, it is important to conduct regular patient examinations. The lowest effective dose of Foster^® should be used (see the “Dosage regimen” section).

Any inhaled corticosteroid can cause systemic effects, especially with long-term use in high doses; it should be noted, however, that the likelihood of these effects with inhaled corticosteroids is much lower than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, cushingoid appearance, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma, and, less commonly, a range of psychological or behavioral effects including psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (especially in children).

Therefore, it is important that such patients are regularly monitored by a doctor and the dose of the inhaled corticosteroid is reduced to the lowest dose that maintains control of asthma symptoms.

Long-term treatment of patients with high doses of inhaled corticosteroids may lead to suppression of adrenal function and the development of acute adrenal insufficiency. Children under 16 years of age taking inhaled doses of beclomethasone dipropionate exceeding the recommended ones are at particular risk. Situations that can potentially trigger the development of acute adrenal insufficiency include: trauma, surgery, infections, or any rapid reduction in the dose of beclomethasone dipropionate. Symptoms of adrenal insufficiency are usually non-specific: anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, low blood pressure, confusion, hypoglycemia, and seizures. During stressful periods and planned surgical interventions, the additional use of systemic corticosteroids should be considered.

If there is reason to believe that adrenal function was impaired during previous systemic corticosteroid therapy, caution should be exercised when transferring patients to treatment with Foster^®.

Patients who are switched from oral corticosteroids to inhaled corticosteroids may be at risk of reduced adrenal reserve. Patients who have required high doses of emergency corticosteroid therapy in the past or who have received long-term treatment with high doses of inhaled corticosteroids may also be at risk. This possibility of residual impairment of adrenal function should always be considered in emergency and planned stressful situations, and therefore, in these cases, the need for appropriate corticosteroid treatment should be considered. In cases of severe adrenal impairment, specialist consultation may be required before planned procedures.

Pneumonia in patients with COPD

An increased incidence of pneumonia, including pneumonia requiring hospitalization, has been observed in COPD patients treated with inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing corticosteroid doses, but this has not been consistently demonstrated in all studies. There is no evidence of differences in the magnitude of pneumonia risk between different inhaled corticosteroids. Physicians should remain vigilant for the possibility of pneumonia in COPD patients, as the clinical manifestations of this type of infection overlap with the symptoms of COPD exacerbation.

Risk factors for the development of pneumonia in COPD patients are smoking, advanced age, low body mass index, and severe COPD.

Visual disturbances

Reports of visual disturbances are possible with systemic and local use of corticosteroids. If a patient develops symptoms such as blurred vision or other visual disturbances, the patient should be referred to an ophthalmologist to assess possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which have been reported with systemic and locally applied corticosteroids.

Oral candidiasis

The patient should be instructed to rinse the mouth and throat with water or brush teeth after inhalation to minimize the risk of developing candidiasis of the oral and pharyngeal mucosa.

Excipients

This drug contains a small amount of ethanol (alcohol), less than 100 mg per dose (approximately 7 mg in one dose). When used at therapeutic doses, the amount of ethanol is very small and does not pose a risk to patients.

Effect on ability to drive and operate machinery

The effect of Foster^® on the ability to drive vehicles and engage in other potentially hazardous activities is unlikely.

Overdose

Inhalation doses of Foster^® up to 12 cumulative aerosol doses (total dose of beclomethasone dipropionate 1200 mcg, formoterol 72 mcg) have been studied in patients with bronchial asthma. Cumulative treatment did not cause adverse effects on vital functions, and no serious or severe adverse effects were observed.

Formoterol

Symptoms: excessively high doses of formoterol can lead to effects typical of beta₂-adrenergic agonists – nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, prolongation of the QT_c interval, metabolic acidosis, hypokalemia, hyperglycemia.

Treatment: if symptoms of formoterol overdose appear, supportive care for basic bodily functions and symptomatic treatment are indicated. In severe cases – hospitalization. The use of cardioselective beta-blockers may be considered with extreme caution, as the use of beta-blockers can cause bronchospasm. Monitoring of plasma potassium levels is necessary.

Beclomethasone dipropionate

A single inhalation of beclomethasone dipropionate doses significantly exceeding the recommended doses may lead to temporary suppression of adrenal cortex function. This usually does not require any emergency measures, since in most cases (based on plasma cortisol level measurements) normal adrenal function is restored within a few days. Such patients should continue treatment at a dose sufficient to control asthma symptoms.

Chronic intake of excessive doses of beclomethasone dipropionate may manifest its systemic effects: significant suppression of the adrenal cortex up to an adrenal crisis may occur. Acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and/or seizures. Situations that can serve as triggers for an acute adrenal crisis include: trauma, surgery, infection, or rapid reduction of the beclomethasone component in Foster^®.

With chronic overdose of beclomethasone dipropionate, there is a risk of suppression of adrenal cortex function. In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex. Treatment should be continued at a dose sufficient to achieve control of asthma symptoms.

Drug Interactions

Pharmacokinetic interaction

Beclomethasone dipropionate undergoes very rapid metabolism by esterase enzymes. Compared to some other corticosteroids, the metabolism of beclomethasone is less dependent on the activity of CYP3A subfamily isoenzymes, so its pharmacokinetic interactions at the metabolism level are unlikely; however, the possibility of systemic effects when used concomitantly with strong inhibitors of CYP3A subfamily isoenzymes (e.g., ritonavir, cobicistat) cannot be excluded, so caution is recommended when using such drugs concomitantly, with appropriate monitoring.

Pharmacodynamic interaction

Beta-adrenergic receptor blockers may weaken or completely negate the effect of formoterol. Foster^® should not be used concomitantly with beta-blockers (including eye drops), except in compelling cases.

When Foster^® is used concomitantly with other beta-adrenergic drugs, an increase in the adverse effects of formoterol is possible, so caution should be exercised when theophylline or other beta-adrenergic drugs are used simultaneously with formoterol.

Concomitant use of Foster^® and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors, and tricyclic antidepressants may prolong the QT_c interval and increase the risk of ventricular arrhythmias.

In addition, levodopa, levothyroxine, oxytocin, and ethanol may reduce the tolerance of the heart muscle to beta₂-adrenergic agonists.

Concomitant use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, may cause an increase in blood pressure.

There is an increased risk of arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbons.

The use of beta₂-adrenergic agonists may cause hypokalemia, which may be enhanced by concomitant treatment with xanthine derivatives, mineralocorticoids, corticosteroids, and diuretics (see the “Special Instructions” section). Hypokalemia may increase the predisposition to arrhythmias in patients taking cardiac glycosides.

Due to the small amount of ethanol in Foster^®, there is a theoretical possibility of interaction in patients taking disulfiram or metronidazole, who have increased sensitivity to ethanol.

Storage Conditions

Before first use of the drug

The drug should be stored out of the reach of children at a temperature between 2°C (35.6°F) and 8°C (46.4°F). Do not freeze.

Shelf Life

The shelf life is 21 months. Do not use after the expiration date.

After first use of the drug

Store for no more than 3 months at a temperature not exceeding 25°C (77°F) within the drug’s shelf life. The date of starting storage at room temperature should be marked on the packaging. Storing the drug in the refrigerator is not allowed.

The canister is under pressure: do not expose to high temperatures (above 50°C (122°F)), do not pierce, do not throw into fire, even when empty.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.