Bufomix isiheiler

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BUFOMIX EASYHALER

Composition:

Active substances: budesonide, formoterol fumarate dihydrate;

One dose contains budesonide 320 mcg and formoterol fumarate dihydrate 9 mcg;

Excipient: lactose monohydrate.

Pharmaceutical form. Powder for inhalation.

Main physicochemical properties: white or yellowish-white powder.

Pharmacotherapeutic group.

Agents used in obstructive airway diseases. Adrenergic agents in combination with corticosteroids or other agents, excluding anticholinergic agents. Formoterol and budesonide. ATC code R03AK07.

Pharmacological properties.

Pharmacodynamics.

Mechanisms of action and pharmacodynamic effects

The medicinal product Bufomix Icihaler contains formoterol and budesonide, which have different mechanisms of action and exhibit additive effects in reducing exacerbations of bronchial asthma. The mechanisms of action of both compounds are described below.

Budesonide. Budesonide is a glucocorticosteroid that, when administered by inhalation, exerts a dose-dependent anti-inflammatory action in the airways, resulting in reduced symptoms of bronchial asthma. Inhaled budesonide is associated with fewer adverse effects compared to systemic corticosteroids. The precise mechanism of the anti-inflammatory effect of glucocorticosteroids is not known.

Formoterol. Formoter0l is a selective β2-adrenergic receptor agonist that, when inhaled, provides rapid and sustained relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilating effect is dose-dependent and occurs within 1–3 minutes. The duration of effect lasts for 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 alleviated symptoms of bronchial asthma, improved lung function, and reduced the frequency of exacerbations.

In two 12-week studies, the effect of budesonide/formoterol on lung function was equivalent to that of budesonide and formoterol administered in a separate combination and superior to budesonide used as monotherapy. All treatment groups used short-acting β2-adrenergic agonists as needed. Over time, no evidence of diminished anti-asthmatic effect was observed.

Two 12-week studies were conducted in pediatric populations, involving 265 children aged 6–11 years who received maintenance therapy with budesonide/formoterol (2 inhalations of 80 mcg/4.5 mcg per inhalation twice daily) and short-acting β2-adrenergic agonists as needed. In both studies, improvements in lung function and adequate tolerability were observed compared to treatment with the corresponding dose of budesonide as monotherapy.

Chronic obstructive pulmonary disease (COPD)

In two 12-month studies, the effect of the drug on lung function and frequency of exacerbations (defined by the number of courses of oral steroids and/or antibiotics and/or hospitalizations) was evaluated in patients with moderate to severe COPD. The inclusion criterion for both studies was a pre-bronchodilator forced expiratory volume in 1 second (FEV1) of <50% of predicted normal. The median post-bronchodilator FEV1 at study entry was 42% of predicted normal.

The annual mean number of exacerbations (as defined above) was significantly reduced in the budesonide/formoterol group compared to monotherapy with formoterol or placebo (mean rate 1.4 vs. 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 per patient per year compared to 11–12 days in the placebo group and 9–12 days in the formoterol group). Regarding changes in lung function parameters such as FEV1, treatment with budesonide/formoterol did not exceed that of formoterol alone.

Pharmacokinetics.

Absorption

Fixed-dose combinations of budesonide and formoterol have been shown to be bioequivalent to the corresponding monoproducts with respect to systemic exposure to budesonide and formoterol, respectively. Nevertheless, after administration of the fixed-dose combination, a slight suppression of cortisol was observed compared to the monoproducts. This difference is considered not to have a clinically relevant impact.

There is no evidence of pharmacokinetic interactions between budesonide and formoterol.

Pharmacokinetic parameters of budesonide and formoterol were comparable after administration as monoproducts or as a fixed-dose combination. For budesonide, the area under the concentration-time curve (AUC) and absorption rate were slightly higher, and the maximum plasma concentration (Cmax) was higher after administration of the fixed-dose combination. For formoterol, Cmax was similar after administration of the fixed-dose combination. Inhaled budesonide is rapidly absorbed, with Cmax reached 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 was approximately 49% of the delivered dose. In children aged 6 to 16 years, lung deposition is within the same range as in adults when the same dose is administered. Resulting plasma concentrations were not detectable.

Inhaled formoterol is rapidly absorbed, with Cmax reached 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 was approximately 61% of the delivered dose.

Distribution and metabolism

Plasma protein binding is approximately 50% for formoterol and 90% for budesonide. The volume of distribution is approximately 4 L/kg for formoterol and 3 L/kg for budesonide. Formoterol is inactivated via conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are predominantly observed as inactivated conjugates). Budesonide undergoes extensive (approximately 90%) first-pass metabolism in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites—6-β-hydroxy-budesonide and 16-α-hydroxyprednisolone—is less than 1% of that of budesonide. There is no evidence of any metabolic interactions or displacement reactions between formoterol and budesonide.

Elimination

The majority of the formoterol dose is transformed via hepatic metabolism, followed by renal excretion. After inhalation, 8–13% of the delivered dose of formoterol is excreted unchanged in urine. Formoterol has a high systemic clearance (approximately 1.4 L/min), and the terminal elimination half-life averages 17 hours.

Budesonide is eliminated via metabolism, primarily catalyzed by the CYP3A4 enzyme. Budesonide metabolites are excreted in urine either in free form or as conjugates. Only very small amounts of unchanged budesonide are found in urine. Budesonide has a high systemic clearance (approximately 1.2 L/min), and the elimination half-life from plasma after intravenous dosing is 4 hours.

The pharmacokinetics of budesonide or formoterol in patients with renal impairment is unknown. The effects of budesonide and formoterol may be increased in patients with liver disease.

Linearity/non-linearity

Systemic exposure to budesonide and formoterol is in linear correlation with the administered dose.

Clinical characteristics.

Indications.

Bronchial asthma

The medicinal product Bufomix Iziheiler (320 mcg/9 mcg) is indicated in adults and adolescents (aged 12 years and older) for regular treatment of bronchial asthma when use of a combination (inhaled corticosteroids and long-acting β2-adrenoceptor agonists) is appropriate:

• in patients in whom adequate control is not achieved with inhaled corticosteroids and short-acting β2-adrenoceptor agonists used as needed;
• in patients in whom adequate control has already been achieved with both inhaled corticosteroids and long-acting β2-adrenoceptor agonists.

Chronic obstructive pulmonary disease (COPD)

The medicinal product Bufomix Iziheiler is indicated for symptomatic treatment in adult patients aged 18 years and older with COPD with FEV1 <70 % of predicted (post-bronchodilator) and a history of exacerbations despite regular bronchodilator therapy.

Contraindications.

Hypersensitivity to budesonide, formoterol, or lactose, which contains a small amount of milk protein.

Interaction with other medicinal products and other forms of interaction.

Pharmacokinetic interactions

Potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, cobicistat, and HIV protease inhibitors) are likely to increase plasma levels of budesonide; therefore, their concomitant use should be avoided. If concomitant use cannot be avoided, the interval between administration of these agents should be as long as possible.

The potent CYP3A4 inhibitor ketoconazole at a dose of 200 mg once daily increases plasma levels of orally administered budesonide (single dose of 3 mg) by an average of 6-fold. When ketoconazole was administered 12 hours after budesonide, plasma concentrations increased on average only 3-fold, indicating that staggered administration may reduce the increase in plasma budesonide levels. Some data suggest that a significant increase in plasma budesonide levels (on average 4-fold) may occur when inhaled budesonide (single dose 1000 mcg) is administered concomitantly with itraconazole at a dose of 200 mg once daily.

Concomitant use of medicinal products containing cobicistat is expected to increase the risk of systemic adverse effects. Combinations should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse effects. In such cases, patients should be monitored for systemic corticosteroid adverse effects.

Pharmacodynamic interactions

β-adrenoceptor blockers may attenuate the effect of formoterol. Therefore, the medicinal product Bufomix Iziheiler should not be used concomitantly with β-adrenoceptor blockers (including ophthalmic drops), unless there are compelling reasons.

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

In addition, levodopa, levothyroxine, 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 cause hypertensive reactions.

The risk of arrhythmia is increased during anaesthesia with halogenated hydrocarbons.

Concomitant use of other β-adrenergic agents or anticholinergic drugs may enhance the bronchodilator effect.

Hypokalaemia may increase susceptibility to cardiac arrhythmia in patients treated with digitalis glycosides.

No interaction between budesonide and formoterol and any of the medicinal products used for the treatment of bronchial asthma has been observed.

Paediatric populations

Drug interaction studies have been conducted only in adults.

Special precautions for use.

It is recommended to gradually reduce the dose when discontinuing the medication and not to stop treatment abruptly.

If patients feel that the treatment is ineffective or there is a need to exceed the maximum recommended dose of Bufomix Iziheiler, they should consult their physician.

Increased use of short-acting bronchodilators indicates worsening of the patient's condition and the need to review bronchial asthma therapy.

Sudden and rapid deterioration in the control of bronchial asthma or COPD may be potentially life-threatening; therefore, the patient should undergo immediate medical evaluation. In such cases, intensification of therapy with corticosteroids, for example a course of oral corticosteroids, or antibiotic treatment in case of infection, should be considered.

Patients should be advised to always carry their inhaler as a rescue medication.

Patients should be reminded to continue taking the maintenance dose of Bufomix Iziheiler as prescribed, even in the absence of symptoms.

Once bronchial asthma symptoms are under control, consideration should be given to gradually reducing the dose of Bufomix Iziheiler. It is important to monitor patients regularly during dose reduction. The lowest effective dose of Bufomix Iziheiler should be used.

Do not initiate treatment with this medicinal product during exacerbations, significant worsening, or sudden complications of bronchial asthma.

Serious adverse reactions and exacerbations related to bronchial asthma may occur during treatment. Patients should be informed about the necessity to continue therapy and simultaneously seek medical advice if asthma symptoms are not controlled or worsen after starting Bufomix Iziheiler.

There are no clinical data on the use of Bufomix Iziheiler in COPD patients with pre-bronchodilator FEV1 >50% of predicted and post-bronchodilator FEV1 <70% of predicted.

As with other forms of inhaled therapy, there is a risk of paradoxical bronchospasm. In such cases, wheezing and shortness of breath increase immediately after inhalation. If paradoxical bronchospasm occurs, Bufomix Iziheiler should be discontinued immediately, the patient should be evaluated, and alternative therapy should be initiated if necessary. Paradoxical bronchospasm responds to fast-acting inhaled bronchodilators and must be treated immediately.

Systemic effects of inhaled corticosteroids may occur, particularly with long-term use of high doses. These effects are much less likely 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, cataract, glaucoma, and, less frequently, various psychological and behavioral disturbances such as psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression (especially in children).

Visual disturbances may occur with systemic and local use of corticosteroids. If a patient reports symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and local corticosteroid use.

Potential effects on bone density should be considered, especially in patients receiving high doses of the drug over a prolonged period and who have concomitant risk factors for osteoporosis. Long-term studies of inhaled budesonide in children at mean daily doses of 400 mcg (delivered dose) or in adults at daily doses of 800 mcg (delivered dose) did not show a significant effect on bone mineral density. Information on the effects of higher doses is lacking.

Caution is required when switching patients from previous systemic steroid therapy to Bufomix Iziheiler, if there is reason to suspect impaired adrenal cortex function.

The benefits of inhaled budesonide therapy generally minimize the need for oral steroids; however, patients transitioning from oral steroids may have a prolonged risk of reduced adrenal reserve. Recovery may be prolonged after discontinuation of oral steroid therapy. Therefore, 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, regular monitoring of the hypothalamic-pituitary-adrenal (HPA) axis function is required.

Prolonged treatment with high doses of inhaled corticosteroids, especially when higher than recommended doses are used, may lead to clinically significant suppression of adrenal cortex function. Therefore, during periods of stress such as severe infections or planned surgery, additional systemic corticosteroid therapy should be considered. Rapid dose reduction of steroids may trigger acute adrenal insufficiency. Symptoms of acute adrenal insufficiency may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension, and hypoglycemia.

Additional systemic steroid therapy or inhaled budesonide must not be stopped abruptly.

When switching from oral steroids to Bufomix Iziheiler, the overall lower systemic steroid effect may lead to the emergence of allergic or arthritic symptoms such as rhinitis, eczema, muscle and joint pain. In such cases, specific treatment should be initiated. General glucocorticoid insufficiency should be suspected if symptoms such as fatigue, headache, nausea, and vomiting appear. In such cases, temporary increase in the dose of oral glucocorticosteroids may sometimes be necessary.

To reduce the risk of oropharyngeal candidiasis, patients should thoroughly rinse their mouth with water after inhaling the maintenance dose. If oropharyngeal candidiasis develops, patients should also rinse their mouth with water after using the medication as needed.

Concomitant treatment with itraconazole, ritonavir, or other potent CYP3A4 inhibitors should be avoided. If this is not possible, the time interval between administration of the drugs should be as long as possible.

Bufomix Iziheiler should be prescribed 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 disorders such as ischemic heart disease, tachyarrhythmia, and severe heart failure.

Caution is required when treating patients with prolonged QTc interval. Formoterol itself may cause QTc interval prolongation.

In patients with active or inactive pulmonary tuberculosis, fungal or viral respiratory infections, the need for and dose of inhaled corticosteroids should be reassessed.

Potentially life-threatening hypokalemia may develop during treatment with high doses of β2-adrenergic agonists. The hypokalemic effect of β2-adrenergic agonists may be enhanced when used concomitantly with other drugs that may cause hypokalemia or enhance its effect, such as xanthine derivatives, steroids, and diuretics. Particular caution is required in patients with unstable bronchial asthma who intermittently use rescue bronchodilators, in acute severe asthma, due to increased risk exacerbated by hypoxia, and in other conditions where the risk of hypokalemia is elevated. In these cases, serum potassium levels should be monitored.

As with other β2-adrenergic agonists, additional monitoring of blood glucose levels is recommended in patients with diabetes mellitus.

Pneumonia in patients with COPD

An increased incidence of pneumonia, including cases requiring hospitalization, has been observed in COPD patients 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 demonstrating intra-class differences in pneumonia risk among inhaled corticosteroid products.

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

Risk factors for pneumonia in COPD patients include smoking, advanced age, low body mass index, and severe COPD.

The medicinal product Bufomix Iziheiler contains approximately 8 mg of lactose per inhalation. This amount usually does not cause problems in patients who are lactose intolerant. The excipient lactose contains a small amount of milk proteins, which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. There are no clinical data on the effects of Bufomix Iziheiler or combined formoterol and budesonide therapy during pregnancy. Animal embryo-fetal development studies did not demonstrate any additional effects of the combination.

There are insufficient data on the use of formoterol in pregnant women. Formoterol caused adverse effects in animals during reproductive toxicity studies at very high systemic exposure levels.

Data from approximately 2000 studied pregnancy cases showed no increased teratogenic risk associated with inhaled budesonide. Animal studies have shown that glucocorticosteroids can cause developmental abnormalities. This is unlikely in humans using the drug at recommended doses.

Animal studies have also shown that excessive prenatal glucocorticoids increase the risk of intrauterine growth retardation, adult cardiovascular diseases, irreversible changes in glucocorticoid receptor density, neurotransmitter turnover, and behavior at concentrations below the teratogenic dose range.

Bufomix Iziheiler should be used during pregnancy only if the expected benefit outweighs the potential risk. The lowest effective dose of budesonide required to maintain adequate asthma control should be used.

Lactation period. Budesonide is excreted in breast milk. However, no effects on the breastfed infant are expected at therapeutic doses. It is unknown whether formoterol is excreted in human breast milk. Small amounts of formoterol have been detected in the milk of animals. The use of Bufomix Iziheiler 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. In animal studies on the effects of formoterol on reproductive function, a slightly reduced fertility rate was observed in male rats at high systemic exposure.

Ability to influence reaction speed when driving or operating machinery.

The medicinal product Bufomix Iziheiler has no effect or negligible effect on the ability to drive vehicles or operate machinery.

Method of Administration and Dosage

Dosing

Bronchial Asthma

The medicinal product Bufomix Easyhaler is not intended for initial treatment of bronchial asthma. The doses of the components of Bufomix Easyhaler are selected individually and adjusted according to the severity of the disease. This should be taken into account not only at the beginning of treatment with combination drugs, but also during adjustment of maintenance dosage. If a patient requires a combination of doses different from those available in the combined inhaler, appropriate doses of β2-adrenergic agonists and/or corticosteroids should be prescribed using separate inhalers.

Recommended doses:

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

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

Patients must undergo regular follow-up examinations by the physician who prescribed Bufomix Easyhaler to ensure that the dose remains optimal. The dose should be titrated to the lowest effective dose that maintains adequate control of symptoms. After achieving long-term control with the lowest recommended dose, consideration should be given to controlling symptoms with inhaled corticosteroid alone.

Once symptom control is achieved with twice-daily administration, the dose should generally be titrated down to the lowest effective dose, including reducing to Bufomix Easyhaler once daily, in cases where, in the physician’s opinion, the patient still requires maintenance therapy with a long-acting bronchodilator in combination with an inhaled corticosteroid.

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

Children (aged 6 years and older): a lower-dose formulation is available for use in children aged 6–11 years (80 mcg/4.5 mcg per dose).

Children under 6 years of age: due to limited data available, Bufomix Easyhaler is not recommended for children under 6 years of age.

Bufomix Easyhaler 320 mcg/9 mcg per dose should be used only for maintenance therapy. For maintenance therapy and symptom relief, lower-strength formulations of Bufomix Easyhaler are available (160 mcg/4.5 mcg per dose and 80 mcg/4.5 mcg per dose).

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 Bufomix Easyhaler in patients with renal or hepatic impairment are lacking. Since budesonide and formoterol are primarily eliminated via hepatic metabolism, increased systemic effects of the drug may be expected in patients with severe hepatic cirrhosis.

Method of Administration

For inhalation use.

How to Use Bufomix Easyhaler Correctly

The inhaler is activated by the airflow during inhalation. This means that when the patient inhales through the mouthpiece, the medication is delivered into the airways along with the inhaled air.

Important points to emphasize to the patient:

• Carefully read the instructions for medical use.
• Shake the device and activate it before each inhalation.
• Inhale through the mouthpiece forcefully and deeply to ensure optimal delivery of the medication to the lungs.
• Do not exhale through the mouthpiece, as this may reduce the delivered dose. If this occurs, the patient should tap the inhaler gently on a hard surface or the palm of the hand to clear the powder from the mouthpiece, then repeat the inhalation procedure.
• Do not activate the device more than once without inhaling the powder. If this occurs, the patient should tap the inhaler on a hard surface or the palm of the hand to clear the powder from the mouthpiece, then repeat the inhalation procedure.
• Always replace the dust-protective cap after using the inhaler to prevent accidental dispersion of powder (which could lead to overdose or delivery of an insufficient dose during the next use).
• Rinse the mouth with water after each dose to minimize the risk of developing oral candidiasis. If oral candidiasis occurs, patients should rinse their mouth with water after inhalations as needed.
• Clean the mouthpiece regularly with a dry cloth. Do not use water for cleaning, as the powder is hygroscopic.
• Replace the Bufomix Easyhaler when the counter displays zero, even if some powder remains visible inside the device.

Children

Bufomix Easyhaler is not recommended for children under 12 years of age for the treatment of bronchial asthma.

In children receiving long-term inhaled corticosteroid therapy, regular monitoring of growth is recommended. If growth retardation occurs, the treatment regimen should be reassessed with the aim of reducing the inhaled corticosteroid dose to the lowest level that maintains effective control of bronchial asthma. The benefits of corticosteroid treatment should be carefully weighed against the risk of growth suppression. In addition, the patient should be referred to a pediatric pulmonologist.

Long-term studies provide evidence that most children and adolescents treated with inhaled budesonide eventually reach their target adult height. However, a small, transient initial reduction in growth (approximately 1 cm) has been observed, typically during the first year of treatment.

Bufomix Easyhaler should not be used in children for the treatment of COPD.

Overdose

Overdose of formoterol may be associated with symptoms typically observed with β2-adrenergic agonist overdose: tremor, headache, tachycardia. In isolated cases, symptoms such as tachycardia, hyperglycemia, hypokalemia, prolonged QTc interval, arrhythmia, nausea, and vomiting have been reported. Supportive and symptomatic treatment is indicated. A dose of 90 mcg administered over three hours in patients with acute bronchial obstruction has been shown to be safe.

Acute overdose of budesonide, even with excessive doses, is not expected to cause clinical problems. However, chronic use of excessive doses may lead to glucocorticoid effects such as hypercorticism and adrenal cortex suppression.

If treatment with Bufomix Easyhaler must be discontinued due to formoterol overdose, appropriate therapy with inhaled corticosteroids should be considered.

Adverse Reactions

Since the medicinal product Bufomix Easyhaler contains both budesonide and formoterol, patients may experience adverse reactions characteristic of these two substances. No increase in the frequency of adverse reactions has been observed following the concomitant use of these two substances. The most commonly reported drug-related adverse reactions correspond to the pharmacologically predictable side effects of β₂-agonist therapy. These include tremor and palpitations, which are usually mild and resolve within a few days.

Adverse reactions associated with budesonide or formoterol are listed below by system organ class and frequency of occurrence. Frequency is defined according to the following scale: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000).

Infections and infestations

Common: Oropharyngeal candidiasis, pneumonia (in patients with COPD).

Immune system disorders

Rare: Immediate or delayed hypersensitivity reactions such as exanthema, urticaria, pruritus, dermatitis, angioneurotic edema, and anaphylactic reaction.

Endocrine disorders

Very rare: Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density.

Metabolism and nutrition disorders

Rare: Hypokalaemia.

Very rare: Hyperglycaemia.

Psychiatric disorders

Uncommon: Aggression, psychomotor hyperactivity, anxiety, sleep disorders.

Very rare: Depression, behavioural changes (mainly in children).

Nervous system disorders

Common: Headache, tremor.

Uncommon: Dizziness.

Very rare: Taste disturbance.

Eye disorders

Uncommon: Blurred vision.

Very rare: Cataract, glaucoma.

Cardiac disorders

Common: Palpitations.

Uncommon: Tachycardia.

Rare: Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles.

Very rare: Angina pectoris, QTc interval prolongation, fluctuations in blood pressure.

Respiratory, thoracic and mediastinal disorders

Common: Mild irritation in the throat, cough, dysphonia including hoarseness.

Rare: Bronchospasm.

Gastrointestinal disorders

Uncommon: Nausea.

Skin and subcutaneous tissue disorders

Uncommon: Bruising.

Musculoskeletal and connective tissue disorders

Uncommon: Muscle cramps.

Oropharyngeal candidiasis is caused by deposition of the drug in the oropharynx. Patients should be advised to rinse the mouth with water after each dose to minimize the risk. Oropharyngeal candidiasis usually responds to local antifungal treatment and does not require discontinuation of inhaled corticosteroids. In case of development of oropharyngeal candidiasis, mouth rinsing with water after drug administration should be performed as needed.

As with other forms of inhaled therapy, paradoxical bronchospasm may occur in rare cases, affecting 1 in 10,000 patients. In such cases, wheezing and shortness of breath increase immediately after dosing. Paradoxical bronchospasm responds to short-acting inhaled bronchodilators and must be treated immediately. Bufomix Easyhaler should be discontinued immediately, the patient should be evaluated, and alternative therapy initiated if necessary.

Systemic effects of inhaled corticosteroids may occur, particularly with long-term use of high doses. These effects are much less likely 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, cataract, and glaucoma. Increased susceptibility to infections and impaired ability to adapt to stress may also develop. These effects are likely dose-, duration-, and patient-dependent, and may also be influenced by concomitant or prior steroid use and individual sensitivity.

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

Paediatric populations

Regular monitoring of growth in children receiving long-term inhaled corticosteroid therapy is recommended.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report suspected adverse reactions via the national reporting system.

Shelf life: 2 years in the laminated pouch.

Use within 4 months after opening the laminated pouch.

Storage conditions.

Prior to opening the laminated pouch, no special storage conditions are required. After opening the laminated pouch, store at a temperature not exceeding 25 °C in a dry place. Keep out of reach of children.

Packaging.

60 doses in an inhaler with a protective cap in a laminated pouch.

1 laminated pouch in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Orion Corporation.

Manufacturer's address.

Orionintie 1, 02200 Espoo, Finland / Orionintie 1, 02200 Espoo, Finland.