INSTRUCTION
for medical use of a medicinal product
BUFOMIKS EASYHALER
(BUFOMIX EASYHALER)
Composition:
active ingredients: budesonide, formoterol fumarate dihydrate;
1 dose contains budesonide 320 mcg and formoterol fumarate dihydrate 9 mcg;
excipient: lactose monohydrate.
Dosage form: Inhalation powder.
Main physicochemical properties: white or yellowish-white powder.
Pharmacotherapeutic group.
Drugs used in obstructive airway diseases. Adrenergic drugs in combination with corticosteroids or other drugs, except anticholinergic drugs. Formoterol and budesonide. ATX code R03A K07.
Pharmacological properties.
Pharmacodynamics.
Mechanisms of action and pharmacodynamic effects
The drug Bufomix Easyhaler contains formoterol and budesonide, which have different modes of action and exhibit additive effects in reducing exacerbations of bronchial asthma. The mechanisms of action of both compounds are discussed below, respectively.
Budesonide. Budesonide is a glucocorticosteroid that, when inhaled, exerts a dose-dependent anti-inflammatory effect in the airways, resulting in a reduction in the symptoms of bronchial asthma. Inhaled budesonide is characterized by less severe adverse effects than systemic corticosteroids. The exact mechanism of the anti-inflammatory effect of glucocorticosteroids is unknown.
Formoterol. Formoterol is a selective β2-adrenoceptor stimulator that, when inhaled, provides rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect is dose-dependent and occurs within 1–3 minutes. The duration of the effect is at least 12 hours after taking a single dose.
Clinical efficacy and safety
Bronchial asthma
Clinical studies in adult patients showed that adding formoterol to budesonide relieved asthma symptoms and improved lung function, as well as reduced the frequency of exacerbations.
In two 12-week studies, the effect of budesonide/formoterol on lung function was similar to that of budesonide and formoterol in any combination and was superior to that of budesonide alone. All treatment groups used short-acting β2-adrenergic agonists as needed. There was no evidence of a loss of antiasthmatic effect over time.
Two 12-week studies were conducted in paediatric populations in which 265 children aged 6-11 years were treated with maintenance doses of budesonide/formoterol (2 inhalations of 80 mcg/4.5 mcg/inhalation twice daily) and a short-acting β2-adrenergic agonist as needed. In both studies, improvements in lung function were observed and the treatment was well tolerated compared with the corresponding dose of budesonide alone.
Chronic obstructive pulmonary disease (COPD)
Two 12-month studies evaluated the effects of the drug on lung function and exacerbation rate (as measured by the number of courses of oral steroids and/or antibiotics and/or hospitalizations) in patients with moderate to severe COPD. Inclusion criteria for both studies were a pre-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted. The median post-bronchodilator FEV1 at baseline was 42% predicted.
The mean number of exacerbations per year (as defined above) was significantly reduced in the budesonide/formoterol group compared with formoterol monotherapy or placebo (mean frequency 1.4 compared with 1.8-1.9 in the placebo/formoterol group). The mean number of days of oral corticosteroids/patient over 12 months was slightly reduced in the budesonide/formoterol group (7-8 days/patient/year compared with 11-12 and 9-12 days in the placebo and formoterol groups, respectively). Regarding changes in lung function parameters such as FEV1, treatment with budesonide/formoterol was not superior to treatment with formoterol alone.
Pharmacokinetics.
Absorption
The fixed-dose combination of budesonide and formoterol and the respective mono-drugs have been shown to be bioequivalent with respect to the systemic exposure of budesonide and formoterol, respectively. However, a slight suppression of cortisol was observed after administration of the fixed-dose combination compared to the mono-drugs. This difference is not considered to have an impact on clinical efficacy.
The pharmacokinetic parameters of budesonide and formoterol were comparable after administration as monotherapy 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 combination. For formoterol, Cmax was similar after administration of the fixed combination. Inhaled budesonide is rapidly absorbed, with Cmax achieved within 30 minutes after inhalation. In studies, the mean lung deposition of budesonide after inhalation using 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 in the same range as in adults after the same dose. The resulting plasma concentrations were not determined.
AND
Inhaled formoterol is rapidly absorbed, with Cmax achieved within 10 minutes after inhalation. In studies, the mean lung deposition of formoterol after inhalation using 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 by conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are mainly observed as inactivated conjugates). Budesonide undergoes extensive (approximately 90%) first-pass biotransformation through 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 the glucocorticosteroid activity of budesonide. There is no evidence of any metabolic interactions or any substitution reactions between formoterol and budesonide.
Breeding
The majority of the formoterol dose is transformed by hepatic metabolism followed by renal excretion. After inhalation, 8–13% of the delivered formoterol dose is excreted in the urine as unchanged formoterol. Formoterol has a high systemic clearance (approximately 1.4 l/min) and a terminal half-life of an average of 17 hours.
Budesonide is eliminated by metabolism, mainly catalyzed by the enzyme CYP3A4. Budesonide metabolites are excreted in the urine in pure or conjugated form. Only very small amounts of unchanged budesonide are found in the urine. Budesonide has a high systemic clearance (approximately 1.2 l/min) and a plasma half-life of 4 hours after an intravenous dose.
The pharmacokinetics of budesonide or formoterol in patients with renal insufficiency are unknown. The exposure to budesonide and formoterol may be increased in patients with liver disease.
Linearity/nonlinearity
Systemic exposure for budesonide and formoterol is linearly correlated with the applied dose.
Clinical characteristics.
Indication.
Bronchial asthma
Bufomix Easyhaler (320 mcg/9 mcg) is indicated in adults and adolescents (aged 12 years and over) for the regular treatment of bronchial asthma when the use of a combination (inhaled corticosteroids and long-acting β2-adrenoceptor agonists) is appropriate:
– patients who are not adequately controlled with inhaled corticosteroids and short-acting β2-adrenergic agonists used as needed;
– patients who have already achieved adequate control with both inhaled corticosteroids and long-acting β2-adrenergic agonists.
Chronic obstructive pulmonary disease (COPD)
Bufomix Easyhaler is indicated for the symptomatic treatment of adult patients aged 18 years and older with COPD with FEV1 <70% predicted normal (after bronchodilator use) and a history of exacerbations despite regular bronchodilator therapy.
Contraindication.
Hypersensitivity to budesonide, formoterol or lactose, which contains small amounts of milk protein.
Interaction with other drugs and other types of interactions.
Pharmacokinetic interactions
The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased the plasma levels of concomitantly administered oral budesonide (single dose 3 mg) by an average of 6-fold. When ketoconazole was administered 12 hours after budesonide, the concentration increased by an average of only 3-fold, suggesting that separate administration may reduce the increase in budesonide plasma levels. Some data suggest that a significant increase in budesonide plasma levels (on average 4-fold) may occur when itraconazole 200 mg once daily is co-administered with inhaled budesonide (single dose 1000 mcg).
Concomitant use of cobicistat-containing medicinal products is expected to increase the risk of systemic adverse reactions. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions. In such cases, patients should be monitored for systemic corticosteroid adverse reactions.
Pharmacodynamic interactions
Beta-blockers may reduce the effect of formoterol. Therefore, Bufomix Easyhaler should not be used together with beta-blockers (including eye drops) unless there are compelling reasons for this.
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 drugs with similar properties such as furazolidone and procarbazine, may cause hypertensive reactions.
The risk of developing arrhythmia increases during anesthesia with halogenated hydrocarbons.
Concomitant use of other β-adrenergic or anticholinergic drugs may enhance the bronchodilator effect.
Hypokalemia may increase the susceptibility to cardiac arrhythmias in patients treated with digitalis glycosides.
No interaction of budesonide and formoterol with any of the drugs used to treat bronchial asthma was observed.
Pediatric populations
Drug interaction studies have only been conducted in adults.
Application features.
It is recommended to gradually reduce the dose when discontinuing the drug and not to stop using it suddenly.
If patients feel that treatment is not effective or need to exceed the highest recommended dose of Bufomix Easyhaler, they should consult a doctor.
More frequent use of immediate-acting bronchodilators indicates a worsening of the patient's condition and the need to review asthma treatment.
Sudden and rapid deterioration in asthma or COPD control is potentially life-threatening and the patient should be evaluated immediately. In such cases, consideration should be given to increasing corticosteroid therapy, such as a course of oral corticosteroids, or antibiotic treatment if infection is present.
The patient should be advised to always carry a rescue inhaler with them.
Patients should be reminded to take their maintenance dose of Bufomix Easyhaler as prescribed, even in the absence of symptoms.
Once asthma symptoms are controlled, consideration should be given to gradually reducing the dose of Bufomix Easyhaler. It is important to review patients regularly when reducing the dose. The lowest effective dose of Bufomix Easyhaler should be used.
Do not start using this medicine during exacerbations, significant worsening or sudden complication of bronchial asthma.
Serious adverse reactions and exacerbations associated with bronchial asthma may occur during the use of the drug. Patients should be informed of the need to continue treatment and to seek medical advice if symptoms of bronchial asthma are not controlled or worsen after starting Bufomix Easyhaler.
There are no clinical trial data on the use of Bufomix Easyhaler in patients with COPD with a pre-bronchodilator FEV1 >50% predicted normal and a post-bronchodilator FEV1 <70% predicted normal.
Paradoxical bronchospasm responds to rapid-acting inhaled bronchodilators and should be treated promptly.
Systemic effects of inhaled corticosteroids may occur, particularly when high doses are used for long periods. These effects are much less likely than those seen with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, glaucoma and, much less frequently, various psychological and behavioral abnormalities, including psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (especially in children).
Visual disturbances may occur with systemic and topical corticosteroids. If a patient reports symptoms such as blurred vision or other visual disturbances, the patient should be referred to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported following the use of systemic and topical corticosteroids.
The potential effect on bone mineral density should be considered, especially in patients taking high doses for long periods of time and who have concomitant risk factors for osteoporosis. Long-term studies of inhaled budesonide in children at average daily doses of 400 mcg (metered dose) or in adults at daily doses of 800 mcg (metered dose) have not shown any significant effect on bone mineral density. There is no information on the effect of high doses.
If there is reason to suspect deterioration of adrenal function due to previous systemic steroid therapy, caution should be exercised when transferring patients to Bufomix Easyhaler therapy.
The benefits of inhaled budesonide therapy usually minimize the need for oral steroids, but patients who are transferred from oral steroids are at risk of having reduced adrenal reserve for a long time. Recovery may be prolonged after discontinuation of oral steroid therapy, so patients who have previously used oral steroids and are transferred to inhaled budesonide may remain at risk for a long time due to impaired adrenal function. In such cases, regular monitoring of hypothalamic-pituitary-adrenal function is necessary.
Prolonged treatment with high doses of inhaled corticosteroids, particularly at doses higher than recommended, may result in clinically significant suppression of adrenal function. Therefore, additional systemic corticosteroid treatment should be considered during periods of stress, such as severe infections and elective surgery. Rapid reduction of steroid doses may precipitate acute adrenal insufficiency. Symptoms that may be seen with acute adrenal insufficiency include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension, and hypoglycemia.
Treatment with additional systemic steroids or inhaled budesonide should not be stopped abruptly.
When switching from oral medication to Bufomix Easyhaler, there is a general lower systemic steroid effect, which may lead to allergic or arthritic symptoms such as rhinitis, eczema, muscle and joint pain. In this case, specific treatment should be initiated. A general insufficient effect of glucocorticosteroids should be suspected if symptoms such as fatigue, headache, nausea and vomiting occur in isolated cases. In such cases, it may be necessary to temporarily increase the dose of oral glucocorticosteroids.
To reduce the risk of oropharyngeal candidiasis, patients should rinse their mouth thoroughly with water after inhalation of the maintenance dose. If oropharyngeal candidiasis occurs, patients should also rinse their mouth with water after use of the drug, if necessary.
Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 inhibitors should be avoided. If this is not possible, the time interval between taking the drugs should be as long as possible.
Bufomix Easyhaler should be administered with caution to 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 should be exercised when treating patients with prolonged QTc interval. Formoterol itself may cause QTc interval prolongation.
Potentially life-threatening hypokalemia may develop during treatment with high doses of β2-adrenoceptor agonists. The hypokalemic effect of β2-adrenoceptor agonists may be enhanced by concomitant treatment with β2-adrenoceptor agonists and drugs that can cause hypokalemia or enhance the hypokalemic effect, such as xanthine derivatives, steroids and diuretics. Particular caution should be exercised in unstable bronchial asthma in the event of intermittent use of rescue bronchodilators, in acute severe bronchial asthma, since the associated risk is increased by hypoxia, as well as in other conditions where the risk of hypokalemia is increased. In these cases, it is recommended to monitor the level of potassium in the blood serum.
As with other β2-adrenergic agonists, additional blood glucose monitoring is required in patients with diabetes.
Pneumonia in patients with COPD
An increased incidence of pneumonia, including pneumonia requiring hospitalization, has been observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid doses, but this has not been demonstrated reliably in all studies.
There is no convincing clinical evidence of intraclass differences in the risk of pneumonia between inhaled corticosteroid preparations.
Physicians should remain alert to the possible development of pneumonia in patients with COPD, as the clinical features of such infections overlap with symptoms of COPD exacerbation.
Risk factors for developing pneumonia in patients with COPD include smoking, older age, low body mass index, and severe COPD.
Bufomix Easyhaler contains approximately 8 mg of lactose per inhalation. This amount is usually not a problem for patients who are lactose intolerant. The excipient lactose contains small amounts of milk proteins which may cause allergic reactions.
Use during pregnancy or breastfeeding.
Pregnancy: There are no clinical data on the effects of Bufomix Easyhaler or concomitant treatment with formoterol and budesonide on pregnancy. Animal embryo-fetal development studies have not shown any additive effect of the combination.
There are no adequate data from the use of formoterol in pregnant women. Formoterol has caused adverse effects in animals in reproductive studies at very high systemic exposure levels.
Data on approximately 2000 exposed pregnancies have not shown an increased teratogenic risk associated with inhaled budesonide. Animal studies have shown that glucocorticosteroids cause malformations. This is unlikely to occur in humans at recommended doses.
Animal studies have also found that excessive prenatal glucocorticoids increase the risk of intrauterine growth retardation, adult cardiovascular disease, irreversible changes in glucocorticoid receptor density, neurotransmitter turnover, and behavior at concentrations below the teratogenic dose range.
During pregnancy, Bufomix Easyhaler should be used only if the expected benefit outweighs the potential risk. The lowest effective dose of budesonide necessary to maintain adequate control of bronchial asthma should be used.
Breastfeeding. Budesonide is excreted in breast milk. However, at therapeutic doses, no effects on the breast-fed child are expected. It is not known whether formoterol is excreted in human milk. Small amounts of formoterol have been detected in animal breast milk. The use of Budesonide Easyhaler in breast-feeding women should only be considered if the expected benefit to the mother outweighs any possible risk to the foetus.
Fertility: There are no data on the potential effects of budesonide on fertility. In animal reproductive studies, formoterol showed a slightly reduced fertility in male rats at high systemic exposure.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
The drug Bufomix Easyhaler has no or negligible influence on the ability to drive and use machines.
Method of administration and doses.
Dosage
Bronchial asthma
Bufomix Easyhaler is not prescribed for the 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 the use of combination drugs, but also when adjusting the maintenance dose. If the patient requires a combination of doses that differs from those available in the combination inhaler, appropriate doses of β2-adrenoceptor agonists and/or corticosteroids in separate inhalers should be prescribed.
Patients should be re-examined regularly by the doctor who prescribed Bufomix Easyhaler to ensure that the dose of this medicine remains optimal. The dose should be titrated to the lowest dose that effectively controls symptoms. After achieving long-term control of symptoms with the lowest recommended dose, symptoms should be controlled with inhaled corticosteroids alone.
Typically, after achieving control of the symptoms of the disease with the use of the drug twice a day, the dose is titrated to the lowest effective dose, including the use of the drug Bufomix Easyhaler 1 time a day, in cases where, in the opinion of the physician, the patient requires maintenance therapy with a long-acting bronchodilator in combination with an inhaled corticosteroid.
More frequent use of an additional rapid-acting bronchodilator indicates a worsening of the patient's condition and the need to review asthma treatment.
Children (age 6 years and older): A lower strength formulation (80 mcg/4.5 mcg/dose) is available for use in children aged 6-11 years.
Children under 6 years of age: As only limited data are available, Bufomix Easyhaler is not recommended for use in children under 6 years of age.
Bufomix Easyhaler 320 mcg/9 mcg/dose should only be used for maintenance therapy. For maintenance therapy and symptom relief with Bufomix Easyhaler, lower strengths (160 mcg/4.5 mcg/dose and 80 mcg/4.5 mcg/dose) are available.
COPD
Recommended doses:
Adults: 1 inhalation 2 times a day.
General information
Special patient groups
There are no special dosage requirements for elderly patients. There are no data on the use of Bufomix Easyhaler in patients with impaired renal or hepatic function. Since budesonide and formoterol are eliminated primarily by hepatic metabolism, increased exposure can be expected in patients with severe cirrhosis of the liver.
Method of application
For inhalation.
How to use Bufomix Easyhaler correctly
The inhaler is flow-controlled. This means that when the patient inhales air through the mouthpiece, the substance enters the airways along with the inhaled air.
It is important to draw the patient's attention to the following:
- Carefully read the instructions for medical use.
- Shake the device and activate it before each inhalation.
- Inhale through the mouthpiece actively and deeply enough to ensure the optimal dose of the substance enters the lungs.
- Do not exhale through the mouthpiece, as this will reduce the dose delivered. If this does happen, tap the inhaler on a table or in the palm of your hand to remove the powder from the mouthpiece, and then repeat the dosing procedure.
- Do not actuate the device more than once without inhaling the powder. If this does happen, the patient should tap the inhaler on a table or the palm of their hand to remove the powder from the mouthpiece, and then repeat the dosing procedure.
- Always put on the dust cap after using the inhaler to prevent accidental spraying of the powder from the device (which could lead to either an overdose or to inhaling an insufficient amount of the medicine the next time you use the inhaler).
- Rinse mouth with water after inhalation of the prescribed dose to minimize the risk of developing oral candidiasis. If oral candidiasis occurs, patients should rinse mouth with water after inhalation 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 inhaler when the counter shows zero, even if some powder is still visible inside the device.
Children.
The drug Bufomix Easyhaler is not recommended for children under 12 years of age for the treatment of bronchial asthma.
In children receiving long-term inhaled corticosteroids, it is recommended that height be measured regularly. If growth is slowed, the treatment regimen should be reviewed with the aim of reducing the dose of inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained. 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.
Overdose.
Overdose with formoterol may be accompanied by symptoms commonly observed with overdose of β2-adrenergic agonists: 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 taken over three hours by patients with acute bronchial obstruction was safe.
In acute overdose of budesonide, even after the use of excessive doses, clinical problems are not expected. In chronic use of excessive doses, glucocorticosteroid effects such as hypercorticism and suppression of the function of the adrenal cortex may occur.
If Bufomix Easyhaler therapy has to be discontinued due to formoterol overdose, appropriate inhaled corticosteroid therapy should be considered.
Adverse reactions.
Since the drug 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 was observed after concomitant administration of these two substances. The most frequent drug-related adverse reactions correspond to the pharmacologically predicted adverse reactions of β2-agonist treatment. These are adverse reactions such as tremor and palpitations, which are usually minor and disappear after a few days.
Adverse reactions associated with budesonide or formoterol are listed below by system organ class and frequency. The frequency is defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
Infectious and parasitic diseases
Common: oropharyngeal candidiasis, pneumonia (in patients with COPD).
On the part of the immune system
Rare: immediate or delayed hypersensitivity reactions such as exanthema, urticaria, pruritus, dermatitis, angioedema and anaphylactic reaction.
From the endocrine system
Very rare: Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density.
Metabolism and nutrition
Rare: hypokalemia.
Very rare: hyperglycemia.
From the psyche
Uncommon: aggression, psychomotor hyperactivity, anxiety, sleep disturbances.
Very rare: depression, behavioral changes (predominantly in children).
From the nervous system
Common: headache, tremor.
Uncommon: dizziness.
Very rare: taste disturbance.
From the organs of vision
Uncommon: blurred vision.
Very rare: cataract and glaucoma.
Cardiovascular system
Common: rapid heartbeat.
Uncommon: tachycardia.
Rare: cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystole.
Very rare: angina pectoris, QTc prolongation, blood pressure fluctuations.
Respiratory, thoracic and mediastinal disorders
Common: moderate throat irritation, cough, dysphonia including hoarseness.
Rare: bronchospasm.
From the digestive system
Uncommon: nausea.
Skin and subcutaneous tissue disorders
Uncommon: bruising.
Musculoskeletal and connective tissue disorders
Uncommon: muscle cramps.
Oropharyngeal candidiasis is caused by drug retention. The patient should be advised to rinse the mouth with water after each dose to minimize the risk. Oropharyngeal candidiasis usually responds to topical antifungal treatment and does not require discontinuation of inhaled corticosteroids. If oropharyngeal candidiasis develops, the mouth should also be rinsed with water after administration, if necessary.
As with other inhalation therapy, paradoxical bronchospasm may occur rarely, affecting up to 1 in 10,000 patients. In this case, the patient experiences increased wheezing and shortness of breath immediately after taking a dose. Paradoxical bronchospasm responds to fast-acting inhaled bronchodilators and should be treated promptly. Bufomix Easyhaler should be discontinued immediately, the patient should be assessed and alternative therapy instituted if necessary.
Systemic effects of inhaled corticosteroids may occur, particularly when high doses are used for long periods. These effects are much less likely than those seen with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Increased susceptibility to infections and impaired ability to adapt to stress may occur. These effects are likely to be dose-related, time-dependent, concomitant or previous steroid use, and individual sensitivity.
Treatment with β2-agonists may lead to increased levels of insulin, free fatty acids, glycerol and ketone bodies in the blood.
Pediatric populations
It is recommended to regularly monitor the growth of children who use inhaled corticosteroids for a long time.
It is important to report suspected adverse reactions after a medicinal product has been authorised. This allows for continuous 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 a laminated package.
Use within 4 months after opening the laminated package.
Storage conditions.
Before the lamino is revealed
