Eirbufo forspiro

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT EIRBUFO FORSPIRO (AIRBUFO® FORSPIRO®)

Composition:

Active substances: budesonide, formoterol fumarate dihydrate;

1 dose contains 160 mcg of budesonide and 4.5 mcg of formoterol fumarate dihydrate or 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate;

Excipient: lactose monohydrate.

Pharmaceutical form. Powder for inhalation, metered.

Main physicochemical properties: powder from white to almost white or light yellow, free of agglomerates.

Pharmacotherapeutic group. Adrenergic agents in combination with corticosteroids or other drugs, excluding anticholinergic agents. Formoterol and budesonide.

ATC code R03AK07.

Pharmacological Properties

Pharmacodynamics

Mechanisms of Action and Pharmacodynamic Effects

The medicinal product Eurbufo Forspiro contains formoterol and budesonide, which have different mechanisms of action and exhibit an additive effect in reducing the frequency of asthma exacerbations. The mechanisms of action of both components are described below.

Budesonide

Budesonide is a glucocorticosteroid that, when inhaled, exerts a dose-dependent anti-inflammatory action in the airways, leading to a reduction in symptoms and a decreased frequency of asthma exacerbations. Inhaled budesonide causes fewer adverse reactions compared to systemic corticosteroids. The precise mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.

Formoterol

Formoterol is a selective β2-adrenergic agonist that, when administered by inhalation, induces rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect is dose-dependent, with onset of action within 1–3 minutes. The duration of effect lasts at least 12 hours after a single dose.

Clinical Efficacy and Safety

Bronchial Asthma

Clinical studies in adult patients have shown that adding formoterol to budesonide alleviates asthma symptoms, improves lung function, and reduces the frequency of exacerbations. In two 12-week studies, the effect of the fixed combination of budesonide/formoterol on lung function was equivalent to that of the free combination of budesonide and formoterol, and superior to budesonide monotherapy. All treatment groups used short-acting β2-adrenoceptor agonists as needed. No evidence of a waning anti-asthmatic effect over time was observed.

Two 12-week studies were conducted in pediatric patients, in which 265 individuals aged 6–11 years received maintenance therapy with budesonide/formoterol (2 inhalations of 80 mcg/4.5 mcg/inhalation twice daily) and short-acting β2-adrenoceptor agonists as needed. In both studies, improvements in lung function and an acceptable safety profile were observed compared to treatment with the corresponding dose of budesonide as monotherapy.

COPD

Two 12-month studies evaluated the effect of the medicinal product on lung function and the frequency of exacerbations (defined by the number of courses of oral steroids and/or antibiotics and/or hospitalizations) in patients with moderate to severe COPD. The inclusion criterion for both studies was a pre-bronchodilator FEV1 of < 50% of predicted normal. The median post-bronchodilator FEV1 at study entry was 42% of predicted normal.

The mean number of exacerbations per year (as defined above) was significantly reduced in the budesonide/formoterol group compared to formoterol monotherapy or placebo (mean rate 1.4 versus 1.8–1.9 in the placebo/formoterol groups). The mean number of days of oral corticosteroid use per patient over 12 months was slightly reduced in the budesonide/formoterol group (7–8 days/patient/year compared to 11–12 days in the placebo group and 9–12 days in the formoterol group). Regarding changes in pulmonary function parameters such as FEV1, treatment with budesonide/formoterol was not more effective than treatment with formoterol alone.

Pharmacokinetics

Absorption

Fixed-dose combinations of budesonide and formoterol were bioequivalent to the corresponding monoproducts with respect to systemic exposure to budesonide and formoterol. Nevertheless, after administration of the fixed-dose combination, a slight increase in cortisol secretion suppression was observed compared to administration of the drugs separately. This difference was considered clinically insignificant.

There was no evidence of pharmacokinetic interaction between budesonide and formoterol.

Pharmacokinetic parameters of the respective substances were similar after administration of budesonide and formoterol as monoproducts and in fixed-dose combinations. After administration of the combination product, the AUC of budesonide, absorption rate, and maximum plasma concentration were slightly higher. The maximum plasma concentration of formoterol after administration of the fixed combination was similar to that after administration of the monoproduct. Inhaled budesonide is rapidly absorbed; plasma concentration reaches its peak within 30 minutes after inhalation. In studies, the mean lung deposition of budesonide after inhalation via a dry powder inhaler ranged from 32% to 44% of the delivered dose. Systemic bioavailability is approximately 49% of the delivered dose. In children aged 6–16 years, lung deposition is within the same range as in adults at the same doses. Corresponding plasma concentrations were not detectable.

Inhaled formoterol is rapidly absorbed; plasma concentration reaches its peak within 10 minutes after inhalation. In studies, the mean lung deposition of formoterol after inhalation via a dry powder inhaler ranged from 28% to 49% of the delivered dose. Systemic bioavailability is approximately 61% of the delivered dose.

Distribution and Metabolism

Approximately 50% of formoterol and 90% of budesonide are bound to plasma proteins. The volume of distribution is approximately 4 L/kg for formoterol and 3 L/kg for budesonide. Formoterol is inactivated via conjugation reactions (producing active O-demethylated and deformylated metabolites, but these are predominantly present as inactivated conjugates). Budesonide undergoes extensive (approximately 90%) biotransformation during first-pass metabolism in the liver, forming metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites, 6-β-hydroxy-budesonide and 16-α-hydroxy-prednisolone, does not exceed 1% of the activity of budesonide. There is no evidence of metabolic interaction or displacement reactions between formoterol and budesonide.

Elimination

The majority of the formoterol dose undergoes hepatic metabolism and is subsequently excreted by the kidneys. After inhalation, 8–13% of the administered dose of formoterol is excreted unchanged in urine.

Formoterol has a high systemic clearance (approximately 1.4 L/min), and its terminal half-life averages 17 hours.

Budesonide is metabolized primarily by the CYP3A4 enzyme. Budesonide metabolites are excreted in urine in unchanged or conjugated forms. Only a small amount of unchanged budesonide is detected in urine. Budesonide has a high systemic clearance (approximately 1.2 L/min), and its plasma half-life after intravenous administration is approximately 4 hours.

The pharmacokinetics of budesonide or formoterol in children and patients with renal impairment are unknown. In patients with liver disease, systemic exposure to budesonide and formoterol may be increased.

Linearity/Non-linearity

Systemic exposure to budesonide and formoterol is linearly correlated with the administered dose.

Clinical characteristics

Indications

Bronchial asthma

Eurbufo Forspiro is indicated in adults and children aged 12 years and older for regular treatment of bronchial asthma when combined therapy (inhaled corticosteroid and long-acting β2-adrenergic agonist) is appropriate:

• when their condition is not adequately controlled with inhaled corticosteroids and as-needed short-acting β2-adrenergic agonists, or
• when their condition is well controlled with inhaled corticosteroids and long-acting β2-adrenergic agonists.

Chronic obstructive pulmonary disease (COPD)

Eurbufo Forspiro is indicated for symptomatic treatment in adult patients aged 18 years and older with COPD and forced expiratory volume in 1 second (FEV1) < 70 % of predicted (post-bronchodilator) and a history of exacerbations despite regular bronchodilator therapy.

Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in the section "Composition" (lactose, which contains a small amount of milk proteins).

Interaction with other medicinal products and other forms of interactions

Pharmacokinetic interactions

Plasma levels of budesonide may markedly increase when the medicinal product is used concomitantly with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, and HIV protease inhibitors); therefore, concomitant use of these medicinal products should be avoided. If this is not possible, the interval between administration of the inhibitor and budesonide should be as long as possible (see section "Special precautions for use").

Concomitant use of Eurbufo Forspiro for maintenance therapy and symptom relief is not recommended in patients taking potent CYP3A4 inhibitors.

The potent CYP3A4 inhibitor ketoconazole, administered at a dose of 200 mg once daily, increased the plasma concentration of oral budesonide (3 mg as a single dose) on average by 6-fold when administered concomitantly. When ketoconazole was administered 12 hours after budesonide, budesonide concentrations increased on average by 3-fold, indicating that staggered administration with an interval between the drugs may reduce the increase in plasma budesonide concentrations. Limited data on this interaction with high doses of inhaled budesonide show that when itraconazole 200 mg once daily was co-administered with inhaled budesonide (1000 mcg as a single dose), plasma levels of budesonide may markedly increase (on average by four-fold).

Pharmacodynamic interactions

Beta-blockers may attenuate or antagonize the effect of formoterol. Therefore, the medicinal product should not be used concomitantly with beta-blockers (including ophthalmic drops), unless there are compelling reasons.

Concomitant use of quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.

In addition, L-dopa, L-thyroxine, oxytocin, and alcohol may impair cardiac tolerance to β2-sympathomimetics.

Concomitant use of monoamine oxidase inhibitors, including medicinal products with similar properties such as furazolidone and procarbazine, may provoke hypertensive reactions.

Patients receiving concomitant anaesthesia with halogenated hydrocarbons are at increased risk of developing arrhythmias.

Concomitant use of other β-adrenergic or anticholinergic medicinal products may have a potentially additive bronchodilator effect.

Hypokalaemia may increase susceptibility to arrhythmias in patients taking cardiac glycosides.

Hypokalaemia may occur as a result of β2-agonist therapy and may be potentiated by concomitant use of xanthine derivatives, corticosteroids, and diuretics (see section "Special precautions for use").

No interactions between budesonide and formoterol with any other medicinal products used for the treatment of bronchial asthma have been observed.

Children. Drug interaction studies have been conducted only in adults.

Special precautions for use

If discontinuation of treatment is necessary, it is recommended to gradually reduce the dose rather than abruptly stop therapy.

Patients should rinse their mouth with water after each inhalation of the maintenance dose to minimize the risk of oropharyngeal candidiasis (see section "Adverse reactions"). If oral thrush develops in the oropharynx, patients should also rinse their mouth with water after additional inhalations used to treat symptoms.

Patients should consult a physician if they consider the treatment ineffective or if the maximum recommended daily dose of Eirbufo Forspiro has been exceeded (see section "Dosage and administration"). More frequent use of short-acting bronchodilators indicates worsening of the patient's condition and the need to reassess bronchial asthma treatment. Sudden and progressive deterioration in control of bronchial asthma or COPD is potentially life-threatening; therefore, the patient should undergo urgent medical evaluation. In such cases, the need for intensified corticosteroid therapy should be considered, for example, initiating a course of oral corticosteroids or antibiotic treatment if bacterial infection is present.

Patients should be advised to always carry a "rescue" inhaler.

Patients should be reminded of the necessity to continue maintenance treatment with Eirbufo Forspiro as prescribed, even when they are asymptomatic.

After achieving control of bronchial asthma symptoms, a gradual reduction in the dose of Eirbufo Forspiro may be considered. It is important that the patient undergoes regular monitoring. The lowest effective dose of Eirbufo Forspiro should be used (see section "Dosage and administration").

Patients should not initiate treatment with Eirbufo Forspiro during an exacerbation or acute or significant worsening of bronchial asthma.

Serious adverse reactions related to bronchial asthma or disease exacerbation may occur during treatment with Eirbufo Forspiro. Patients should continue treatment and consult a physician if symptoms of bronchial asthma do not resolve or worsen after starting therapy with Eirbufo Forspiro.

There are no clinical data on the use of Eirbufo Forspiro in COPD patients with pre-bronchodilator FEV1 > 50% of predicted and post-bronchodilator FEV1 < 70% of predicted (see section "Pharmacodynamics").

As with any other inhaled therapy, paradoxical bronchospasm with immediate increase in wheezing and shortness of breath after drug administration may occur. If a patient develops paradoxical bronchospasm, treatment with Eirbufo Forspiro should be discontinued immediately, the patient's condition should be evaluated, and alternative therapy initiated if necessary. Paradoxical bronchospasm, which requires immediate treatment, responds to administration of a rapid-acting inhaled bronchodilator (see section "Adverse reactions").

Systemic effects may occur with inhaled administration of all corticosteroids, especially at high doses and during prolonged treatment. The likelihood of such effects is considerably lower with inhaled corticosteroids compared to oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineral density, cataract and glaucoma, and less frequently, psychiatric disturbances or behavioral changes, including psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression (especially in children) (see section "Adverse reactions").

The potential impact on bone mineral density should be considered, particularly in patients receiving high doses over a prolonged period, which represents an additional risk factor for osteoporosis. In long-term studies of inhaled budesonide at average daily doses of 400 mcg (delivered dose) in children or 800 mcg (delivered dose) in adults, no significant effect on bone mineral density was observed. Information on the effect of Eirbufo Forspiro at higher doses is lacking.

If there is reason to suspect that adrenal function has been impaired due to prior systemic steroid therapy, caution should be exercised when switching patients to treatment with Eirbufo Forspiro.

The benefits of inhaled budesonide therapy generally minimize the need for oral steroids, but patients previously receiving long-term oral steroids may still be at risk of adrenal dysfunction. Recovery after discontinuation of oral steroids may take a considerable amount of time; thus, patients previously treated with oral steroids and switched to inhaled budesonide may remain at risk for a prolonged period due to adrenal dysfunction. In such cases, hypothalamic-pituitary-adrenal (HPA) axis function should be monitored regularly.

Prolonged treatment with high doses of inhaled corticosteroids, particularly when doses higher than recommended are used, may also lead to clinically significant adrenal suppression. Therefore, additional systemic steroid therapy should be considered during periods of stress (e.g., during severe infections) or planned surgical procedures. Rapid dose reduction of steroids may precipitate an acute adrenal crisis. Symptoms and signs that may occur during an acute adrenal crisis may be somewhat nonspecific but may include anorexia, abdominal pain, weight loss, increased fatigue, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension, and hypoglycemia.

Treatment with additional systemic steroids or inhaled budesonide should not be abruptly discontinued.

During transition from oral steroid therapy to Eirbufo Forspiro, a lower systemic steroid effect is generally observed, which may lead to the emergence of allergy symptoms or arthritis symptoms such as rhinitis, eczema, and muscle and joint pain. If these conditions develop, specific treatment should be initiated. Glucocorticoid insufficiency should generally be suspected if, in rare cases, symptoms such as increased fatigue, headache, nausea, and vomiting occur. In such cases, temporary increase in the dose of oral glucocorticoids may sometimes be necessary.

To reduce the risk of oropharyngeal candidiasis (see section "Adverse reactions"), patients should be instructed to rinse their mouth with water after each inhalation of the maintenance dose.

Concomitant use of itraconazole, ritonavir, or other potent CYP3A4 inhibitors should be avoided (see section "Interaction with other medicinal products and other forms of interaction"). If this is not possible, the time interval between administration of interacting medicinal products should be as long as possible.

Eirbufo Forspiro should be used with caution in patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, untreated hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm, or other severe cardiovascular diseases such as ischemic heart disease, tachyarrhythmia, or severe heart failure.

The drug should be used with caution in patients with prolonged QTc interval. Formoterol may cause QTc interval prolongation.

The need for inhaled corticosteroids and their dosage should be reassessed in patients with active or inactive pulmonary tuberculosis, or fungal or viral respiratory tract infections.

With high-dose use of β2-adrenergic agonists, potentially serious hypokalemia may occur. When β2-adrenergic agonists are used concomitantly with medicinal products that may cause hypokalemia or enhance its effect (e.g., xanthine derivatives, steroids, and diuretics), the hypokalemic effect of β2-adrenergic agonists may be intensified. Particular caution is required in patients with unstable bronchial asthma receiving various short-acting bronchodilators or in acute severe asthma, as the risk of hypokalemia is increased in the presence of hypoxia and other conditions that increase the likelihood of complications such as hypokalemia. In such cases, serum potassium levels should be monitored.

As with other β2-adrenergic agonists, blood glucose levels should be monitored more closely in patients with diabetes mellitus.

Visual disturbances may occur with systemic or local use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should consult an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which has been reported after systemic or local corticosteroid use.

Eirbufo Forspiro contains lactose monohydrate (< 1 mg/inhalation). This amount usually does not cause problems in patients with lactose intolerance. However, this excipient contains small amounts of milk proteins that may cause allergic reactions.

Pneumonia in patients with COPD

An increased incidence of pneumonia, including cases requiring hospitalization, has been observed in patients with COPD receiving inhaled corticosteroids. Some data suggest an increased risk of pneumonia with higher steroid doses, although this has not been consistently demonstrated in all studies.

There are no convincing clinical data showing differences in pneumonia risk among inhaled corticosteroid medicinal products.

Physicians should remain vigilant for possible development of pneumonia in patients with COPD, as clinical signs of such infections overlap with symptoms of COPD exacerbation.

Risk factors for pneumonia in patients with COPD include smoking, older age, low body mass index (BMI), and severe COPD.

Children

Regular monitoring of growth in children receiving long-term inhaled corticosteroids is recommended. If growth retardation occurs, therapy should be reassessed with the aim of reducing the inhaled corticosteroid dose to the lowest dose at which effective control of asthma symptoms is maintained, if possible. The benefits of corticosteroid use and the potential risk of growth retardation should be carefully weighed. Additionally, referral to a pediatric respiratory specialist may be appropriate.

Due to limited long-term data on glucocorticoid treatment, it can be assumed that most children receiving inhaled budesonide therapy will eventually achieve normal adult height. However, an initial slight and transient reduction in growth velocity (approximately 1 cm) has been observed. This delay is typically noted during the first year of treatment.

Use during pregnancy or breastfeeding

Pregnancy

There are no clinical data on the use of Eirbufo Forspiro or concomitant therapy with formoterol and budesonide during pregnancy. Data from studies on the effect of this combination on embryofetal development in rats did not reveal any signs of additional effects with combination use.

Sufficient data on the use of formoterol in pregnant women are lacking. Reproductive toxicity studies in animals showed adverse effects with formoterol at very high systemic doses.

Data from approximately 2000 pregnancies did not show any increased teratogenic risk associated with inhaled budesonide. Animal studies have demonstrated that glucocorticoids may cause congenital malformations. However, these findings are likely not relevant to humans when the medicinal product is used at recommended doses.

Animal studies have also shown that high-dose glucocorticoid use during pregnancy increased the risks of intrauterine growth retardation, development of cardiovascular disease in adult animals, and permanent changes in glucocorticoid receptor density, metabolism, and neurotransmitter profiles when administered at doses below teratogenic levels.

Eirbufo Forspiro may be used during pregnancy only if the benefit of treatment outweighs the potential risks. The lowest effective dose of budesonide that provides adequate control of bronchial asthma symptoms should be used.

Breastfeeding

Budesonide passes into breast milk. However, no effect on the infant is expected with therapeutic doses. It is unknown whether formoterol passes into human breast milk.

In rats, small amounts of formoterol were detected in milk. The use of Eirbufo Forspiro in breastfeeding women should be considered only if the expected benefit to the mother outweighs any potential risk to the infant.

Fertility

There are no data on the potential effect of budesonide on fertility. Studies on the effect of formoterol on reproductive function in animals showed a slightly reduced fertility in male rats at high systemic exposure.

Ability to affect reaction speed when driving or operating machinery

Eirbufo Forspiro has no effect or negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Route of administration: inhalation.

Dosage 160 mcg/4.5 mcg

Bronchial Asthma

Eirboufo Forspiro is not indicated for initial treatment of bronchial asthma. The doses of the components of Eirboufo Forspiro should be individually adjusted and modified according to the severity of the disease. This should be taken into account not only at the beginning of treatment with combination medicinal products but also when adjusting the maintenance dose. If a patient requires a dose combination different from those available in the combined inhaler, appropriate doses of β2-adrenergic agonists and/or corticosteroids should be prescribed using separate inhalers.

The dose should be gradually reduced to the lowest dose that effectively controls symptoms. Patients should undergo regular follow-up examinations by the physician who prescribed the medicinal product to ensure the dose of Eirboufo Forspiro remains optimal. After achieving long-term symptom control with the lowest recommended dose, consideration should be given to controlling symptoms with an inhaled corticosteroid alone.

There are two options for using Eirboufo Forspiro:

A. Use of the medicinal product for maintenance therapy: Eirboufo Forspiro is used for regular maintenance therapy in combination with a separate short-acting bronchodilator used as needed for symptom relief.

B. Use of the medicinal product for maintenance therapy and symptom relief: Eirboufo Forspiro is used for regular maintenance therapy and also as needed for symptom relief.

A. Use of the medicinal product for maintenance therapy

Patients should be advised to always carry a separate short-acting bronchodilator for immediate symptom relief.

Recommended doses

Adults (aged 18 years and older): 1–2 inhalations twice daily. Some patients may require up to 4 inhalations twice daily.

Children (aged 12–17 years): 1–2 inhalations twice daily.

After achieving symptom control with twice-daily administration, the dose is usually titrated to the lowest effective dose, including reducing to once-daily administration of Eirboufo Forspiro, when, in the physician’s opinion, the patient requires maintenance therapy with a long-acting bronchodilator in combination with an inhaled corticosteroid.

An increased use of a separate short-acting bronchodilator indicates worsening of the underlying disease and requires re-evaluation of bronchial asthma treatment.

B. Use of the medicinal product for maintenance therapy and symptom relief

Patients should take the daily maintenance dose of Eirboufo Forspiro and also use this medicinal product as needed for symptom relief. Patients should be advised to always carry Eirboufo Forspiro for immediate symptom relief in emergency situations. Patients using Eirboufo Forspiro for symptom relief should discuss with their physician the possibility of using this medicinal product for prevention of bronchoconstriction induced by allergens or physical exertion; in such cases, the frequency of as-needed use should be considered. If frequent use of bronchodilators is required without a corresponding need to increase the dose of inhaled corticosteroids, alternative medicinal products for symptom relief should be considered.

The use of Eirboufo Forspiro for maintenance therapy and symptom relief should be considered, in particular, for patients:

• with inadequate control of bronchial asthma who frequently require symptom-relief medications;
• with a history of asthma exacerbations requiring medical intervention.

Patients who frequently and in large quantities use Eirboufo Forspiro inhalations as needed should be carefully monitored for the development of dose-dependent adverse reactions.

Recommended doses

Adults and children aged 12 years and older: The recommended maintenance dose is 2 inhalations daily: 1 inhalation in the morning and 1 in the evening, or 2 inhalations either in the morning or in the evening. Some patients may require a maintenance dose of 2 inhalations twice daily. As needed, 1 additional inhalation should be taken if symptoms occur. If symptoms do not resolve within a few minutes, an additional inhalation may be taken. In any single episode, no more than 6 inhalations should be used.

A total daily dose exceeding 8 inhalations is generally not required; however, during a limited period, the total daily dose may reach up to 12 inhalations. Patients using more than 8 inhalations per day are strongly advised to consult their physician. They should undergo re-evaluation and review of their maintenance therapy regimen.

Children under 12 years of age: Eirboufo Forspiro is not recommended for maintenance therapy and symptom relief in children under 12 years of age.

Chronic Obstructive Pulmonary Disease (COPD)

Recommended doses

Adults: 2 inhalations twice daily.

Dosage (320 mcg/9 mcg)

Bronchial Asthma

Eirboufo Forspiro is not indicated for initial treatment of bronchial asthma. The doses of the components of the medicinal product are individually adjusted and must be modified according to the severity of the disease. This should be considered not only at the beginning of treatment with combination medicinal products but also when adjusting the maintenance dose. If a patient requires a dose combination different from those available in the combined inhaler, appropriate doses of β2-adrenergic agonists and/or corticosteroids should be prescribed using separate inhalers.

Patients should undergo regular follow-up examinations by the physician who prescribed the medicinal product to ensure the dose of Eirboufo Forspiro remains optimal. The dose should be gradually reduced to the lowest dose that effectively controls symptoms. After achieving long-term symptom control with the lowest recommended dose, consideration should be given to controlling symptoms with an inhaled corticosteroid alone.

After achieving symptom control with twice-daily administration, the dose is usually titrated to the lowest effective dose, including reducing to once-daily administration of Eirboufo Forspiro, when, in the physician’s opinion, the patient requires maintenance therapy with a long-acting bronchodilator.

Increased use of a separate short-acting bronchodilator indicates worsening of the patient’s condition and the need to re-evaluate treatment for bronchial asthma.

Eirboufo Forspiro in the 320 mcg/9 mcg dosage should be used only for maintenance therapy.

For maintenance therapy and symptom relief, the lower-strength formulation of Eirboufo Forspiro (160 mcg/4.5 mcg) is available.

Recommended doses

Adults (aged 18 years and older): 1 inhalation twice daily. Some patients may require up to 2 inhalations twice daily.

Children (aged 12–17 years): 1 inhalation twice daily.

Chronic Obstructive Pulmonary Disease (COPD)

Recommended doses

Adults: 1 inhalation twice daily.

General Information

Special patient groups

No special dosage requirements are necessary for elderly patients. Data on the use of the medicinal product in patients with renal or hepatic impairment are lacking. Since budesonide and formoterol are primarily eliminated via hepatic metabolism, increased plasma concentrations of the medicinal product may be expected in patients with severe liver cirrhosis.

Method of Administration

Instructions for use of Eirboufo Forspiro inhaler

Patients must be instructed on the correct use of the inhaler device, and this should be regularly checked.

The inhaler contains 60 doses of the medicinal product in a blister strip (Fig. 1). It has a dose counter that shows the number of doses remaining, counting down from 60 to 0. When the last 10 doses remain, the numbers will appear on a red background.

The inhaler must not be refilled; it should be disposed of when empty and replaced with a new one.

Fig. 1

Before using the inhaler:

• open the transparent side compartment door;
• carefully detach the blister strip from the "teeth" of the side compartment along its entire length (Fig. 2). Do not pull or jerk the strip;
• close the side compartment door and dispose of the used strip.

Fig. 2

Note: During use, the side compartment will gradually fill with the used strip. Strips with black bands do not contain the medicinal product. Eventually, the numbered sections of the strip will appear in the side compartment. The side compartment should never contain more than 2 sections of the strip, as they may cause the inhaler to jam. The strip should be carefully detached as shown above and safely disposed of.

Using the inhaler

The inhaler should be held as shown in the figures.

1. Open
   • open the protective cap downward to expose the mouthpiece (Fig. 3);
   • check the dose counter to see how many doses remain;

Fig. 3

1. Prepare the dose
   • lift the edge of the white lever upward (Fig. 4); the side compartment must be closed;

Fig. 4

Note: The white lever should only be used when the patient is ready to inhale the dose. Playing with the white lever will waste doses.

• open: fully move the white lever to the stop until a click is heard (Fig. 5); this action advances a new dose to the top position;

Fig. 5

• close: then fully close the white lever until it clicks and returns to its original position (Fig. 6). The inhaler is now ready for immediate use.

Fig. 6

1. Inhale the dose
   • the patient should exhale as deeply as possible, without holding the inhaler in the mouth;

Never exhale directly into the inhaler, as this may affect the dose;

• hold the inhaler level, with the protective cap facing downward;
• lips should be tightly sealed around the mouthpiece (Fig. 7);
• the patient should inhale as deeply and forcefully as possible through the mouth, not through the nose;

Fig. 7

• remove the inhaler from the mouth and hold breath for 5–10 seconds, or as long as comfortable;
• then the patient should exhale slowly, but not into the inhaler;
• replace the protective cap over the mouthpiece;
• rinse the mouth with water and spit it out. This may help prevent fungal infection in the mouth and hoarseness.

Cleaning:

• if necessary, wipe the outer part of the mouthpiece with a clean, dry cloth;
• do not disassemble the inhaler for cleaning or any other purpose;
• do not clean any parts of the inhaler with water or wet wipes, as moisture may affect the dose;
• never insert pins or other sharp objects into the mouthpiece or any other part of the inhaler, as this may damage the device!

Children

Eirboufo Forspiro is recommended for use in children aged 12 years and older.

Overdose

Overdose of formoterol is likely to cause effects typical of β2-adrenergic agonists: tremor, headache, palpitations. In isolated cases, tachycardia, hyperglycemia, hypokalemia, QTc interval prolongation, arrhythmia, nausea, and vomiting have been reported. Supportive and symptomatic therapy may be indicated. Administration of 90 mcg over 3 hours in patients with acute bronchial obstruction was safe.

Acute overdose of budesonide, even in excessive doses, is not expected to cause clinical problems. However, prolonged use of excessive doses may lead to systemic effects of glucocorticosteroids, such as hypercorticism and adrenal suppression.

If administration of Eirboufo Forspiro must be discontinued due to formoterol overdose, consideration should be given to using an appropriate inhaled corticosteroid.

Adverse reactions

Since Eurbufo Forspiro contains budesonide and formoterol, adverse reactions associated with the use of each of the active substances alone may occur. Concomitant administration of the two substances did not increase the frequency of adverse reactions. The most commonly observed adverse reactions associated with the use of the medicinal product are pharmacologically predictable side effects of β2-adrenoceptor agonists, such as tremor and palpitations. These adverse reactions were generally mild in severity and disappeared within a few days of treatment.

The adverse reactions caused by budesonide or formoterol, listed below, are presented by system organ classes and by frequency of occurrence. Frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000) and very rare (< 1/10,000).

System organ class (SOC)	Frequency	Adverse reaction to drug application medicinal product
Infections and infestations	Common	Oropharyngeal and esophageal candidiasis Pneumonia (in patients with COPD)
Immune system disorders	Uncommon	Immediate or delayed hypersensitivity reactions, such as exanthema, urticaria, pruritus, dermatitis, angioneurotic edema, and anaphylactic reactions
Endocrine disorders	Very rare	Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density
Metabolism and nutrition disorders	Uncommon	Hypokalemia
	Very rare	Hyperglycemia
Psychiatric disorders	Uncommon	Aggression, psychomotor hyperactivity, anxiety, sleep disturbances
	Very rare	Depression, behavioral disturbances (mainly in children)
Nervous system disorders	Common	Headache, tremor
	Uncommon	Dizziness
	Very rare	Disturbance of taste
Eye disorders	Uncommon	Blurred vision (see section "Special precautions for use")
	Very rare	Cataract, glaucoma
Cardiac disorders	Common	Palpitations
	Uncommon	Tachycardia
	Uncommon	Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles
	Very rare	Angina pectoris, QTc interval prolongation
Vascular disorders	Very rare	Changes in blood pressure
Respiratory, thoracic and mediastinal disorders	Common	Mild irritation in the throat, cough, dysphonia including hoarseness
	Uncommon	Bronchospasm
Gastrointestinal disorders	Uncommon	Nausea
Skin and subcutaneous tissue disorders	Uncommon	Increased tendency to bruising
Musculoskeletal and connective tissue disorders	Uncommon	Muscle cramps

Candidiasis of the oropharynx results from deposition of the medicinal product in the oral cavity. Patients should be instructed to rinse the mouth with water after each inhalation of the maintenance dose to minimize the risk of oral candidiasis. Oropharyngeal candidiasis usually responds to local antifungal treatment without the need to discontinue inhaled corticosteroid therapy. In case of development of oropharyngeal candidiasis, patients should also rinse the mouth with water after administration of the medicinal product as needed.

As with any other inhaled therapy, paradoxical bronchospasm with immediate increase in wheezing and shortness of breath after taking a dose of the medicinal product may occur very rarely (less than 1 case per 10,000 patients). Paradoxical bronchospasm, which requires immediate treatment, responds to administration of a fast-acting inhaled bronchodilator. In such a case, the use of the medicinal product Eurbufo Forspiro should be discontinued immediately, the patient's condition should be assessed, and alternative therapy initiated if necessary (see section "Special precautions for use").

Systemic effects may occur with inhaled corticosteroids, especially at high doses and over prolonged periods. The likelihood of such effects is lower with inhaled corticosteroids compared to oral forms. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineral density, cataract, and glaucoma. Increased susceptibility to infections and impaired ability to adapt to stress may also occur. These effects are likely dependent on dose, duration of exposure, influence of concomitant and previously administered steroids, and individual sensitivity.

Treatment with β2-adrenergic agonists may lead to increased blood levels of insulin, free fatty acids, glycerol, and ketone bodies.

Children. Regular monitoring of growth in children who are on long-term inhaled corticosteroid therapy is recommended (see section "Special precautions for use").

Reporting of adverse reactions

Reporting of adverse reactions after medicinal product registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives should report all suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store at temperatures not exceeding 30°C. Keep out of reach of children.

Packaging

60 doses per inhaler containing a blister strip. 1 inhaler per cardboard box.

Prescription status

Prescription only.

Manufacturer

Aeropharm GmbH.

Solutas Pharma GmbH.

Manufacturer's address and place of business

Franz-Mitscherlich-Allee 1, Rudolstadt, 07407, Germany.

Otto-von-Guericke-Allee 1, 39179, Barleben, Saxony-Anhalt, Germany.