Foracort® 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FORACORT®200 (FORACORT 200)

Composition:

Active substances: budesonide; formoterol fumarate, dihydrate;

1 dose (1 inhalation) of the medicinal product contains 200 mcg of budesonide and 6 mcg of formoterol fumarate dihydrate;

Excipient: propellant tetrafluoroethane (propellant-134a).

Pharmaceutical form. Pressurized metered-dose inhalation aerosol.

Main physicochemical characteristics: white, homogeneous, suspended inhalation aerosol contained in a pressurized container.

Pharmacotherapeutic group.

Adrenergic agents in combination with corticosteroids or other drugs, excluding anticholinergic agents. Formoterol and budesonide. ATC code R03AK07.

Pharmacological properties.

Pharmacodynamics.

Foracort®200 contains budesonide and formoterol, therefore the mechanisms of action described below for each component apply to the Foracort®200 preparation. These components belong to two classes of medicinal agents (a synthetic corticosteroid and a selective long-acting β-adrenergic agonist) that exert different effects on the clinical and physiological parameters of asthma.

Budesonide

Budesonide is a glucocorticosteroid with demonstrated glucocorticoid activity and weak mineralocorticoid activity.

Formoterol fumarate

Formoterol fumarate is a selective β2-adrenergic receptor agonist that induces rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect is dose-dependent; onset of action occurs within 1–3 minutes after inhalation, and the effect lasts on average 12 hours after a single dose.

Combination of budesonide/formoterol

Bronchial asthma

Clinical efficacy of maintenance therapy with budesonide/formoterol combination

Clinical studies in adults have shown that adding formoterol to budesonide leads to alleviation of bronchial asthma symptoms and improvement in lung function, as well as reduction in the frequency of disease exacerbations.

Clinical efficacy of maintenance and reliever therapy with budesonide/formoterol combination

Maintenance and reliever therapy with the budesonide/formoterol combination resulted in a statistically and clinically significant reduction in severe exacerbations compared to all other treatments.

In studies involving patients requiring medical attention due to acute bronchial asthma symptoms, the use of budesonide/formoterol combination provided rapid and effective relief from bronchoconstriction, comparable to salbutamol and formoterol.

Chronic obstructive pulmonary disease (COPD)

Effect on lung function and exacerbation rate (defined as number of courses of oral steroids and/or antibiotics and/or hospitalizations) in patients with chronic obstructive lung diseases. The annual mean number of exacerbations (defined as above) was significantly reduced with budesonide/formoterol combination compared to treatment with formoterol alone or placebo.

Pharmacokinetics.

Budesonide

Absorption

Inhaled budesonide is rapidly absorbed in the lungs, with maximum plasma concentration (Cmax) usually achieved within 20 minutes. After oral administration, Cmax in plasma was reached approximately 1–2 hours post-dose, and absolute systemic bioavailability was 6–13% due to extensive presystemic metabolism. In contrast, most of the budesonide delivered to the lungs was systemically absorbed. In healthy volunteers, 34% of the dose remained in the lungs with absolute systemic bioavailability of 39% of the dose.

In patients with bronchial asthma, budesonide showed linear increases in area under the curve (AUC) and Cmax with increasing dose, both after single and repeated inhalation doses.

Distribution

The volume of distribution of budesonide is 3 L/kg. Budesonide is 85–90% bound to plasma proteins. Protein binding is constant at and above concentrations (100 nmol/L) corresponding to the recommended inhaler dose. Budesonide binds minimally or not at all to corticosteroid-binding globulin. Budesonide rapidly equilibrates with erythrocytes independently of concentration, with a blood-to-plasma ratio of approximately 0.8.

Metabolism

In vitro studies using human liver homogenate have shown that budesonide is rapidly and extensively metabolized. The two main metabolites are 6-β-hydroxybudesonide and 16-α-hydroxyprednisolone. Their activity does not exceed 1% of budesonide's activity. No qualitative differences were observed between in vitro and in vivo metabolic profiles. Minor metabolic inactivation has been observed in human lung tissue and blood serum.

Elimination

Budesonide is eliminated from the body via urine and feces as metabolites. Approximately 60% of an intravenously administered radiolabeled dose was excreted in urine.

No unchanged budesonide was detected in urine. The 22R-form of budesonide is predominantly cleared by the liver with a systemic clearance of 1.4 L/min compared to 1 L/min for the 22S-form. The elimination half-life (2–3 hours) is similar for both epimers and is independent of dose.

Formoterol fumarate

Absorption

Inhaled formoterol is rapidly absorbed; Cmax is usually reached at the first plasma sampling within 5–10 minutes after administration. As with most inhaled drugs, the majority of inhaled formoterol is swallowed and subsequently absorbed from the gastrointestinal tract.

Distribution

At concentrations of 10–500 nmol/L, plasma protein binding of the (R,R)- and (S,S)-enantiomers of formoterol is 46% and 58%, respectively. The formoterol concentration used to assess plasma protein binding was higher than the concentration achieved in plasma after inhalation of a single 54 mcg dose.

Metabolism and elimination

It has been reported that 62% of radiolabeled formoterol is excreted in urine and 2.4% in feces. Formoterol is metabolized via direct conjugation with glucuronic acid and O-demethylation to inactive metabolites. Another metabolic pathway involves deformylation and sulfate conjugation. CYP2D6 and CYP2C are primarily responsible for O-demethylation.

The pharmacokinetics of budesonide and formoterol in patients with renal impairment is unknown. In patients with hepatic disease, plasma concentrations of budesonide and formoterol may be increased.

Clinical characteristics.

Indications.

Bronchial asthma

Foracort®200 is indicated for regular treatment of bronchial asthma in adults and children aged 12 years and older when combined therapy (inhaled corticosteroids and long-acting β2-agonists) is appropriate:

• in patients whose condition is not adequately controlled with inhaled corticosteroids and short-acting β2-agonists used as needed, or
• in patients whose condition is well controlled with inhaled corticosteroids and long-acting β2-agonists.

Chronic obstructive pulmonary disease (COPD)

The medicinal product is indicated for symptomatic treatment of adult patients aged 18 years and older with severe COPD (forced expiratory volume in 1 second (FEV1) < 70 % of predicted) following bronchodilator use and with a history of repeated exacerbations with significant symptoms despite regular therapy with long-acting bronchodilators.

Contraindications.

Hypersensitivity to budesonide, formoterol, or the propellant tetrafluoroethane (propellant-134a).

Interaction with other medicinal products and other types of interactions.

Pharmacokinetic interaction

Plasma levels of budesonide may increase significantly when the 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 agents should be avoided. If avoidance is not possible, the time interval between administration of the inhibitor and budesonide should be as long as possible (see section "Special precautions for use"). Foracort®200 is not recommended for maintenance and reliever therapy in patients taking potent CYP3A4 inhibitors.

The potent CYP3A4 inhibitor ketoconazole, administered at a dose of 200 mg once daily, increases the plasma concentration of oral budesonide (3 mg as a single dose) by an average of 6-fold when co-administered. When ketoconazole is administered 12 hours after budesonide, the budesonide concentration increases on average by 3-fold, indicating that separated administration with a time interval may reduce the increase in plasma budesonide concentration. Limited data on this interaction with high doses of inhaled budesonide show that co-administration of itraconazole 200 mg once daily with inhaled budesonide (1000 mcg as a single dose) may significantly increase budesonide plasma levels (on average by 4-fold).

Pharmacodynamic interaction

Beta-adrenergic blockers may attenuate or antagonize the effects of formoterol. Therefore, Foracort®200 should not be taken concomitantly with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.

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

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

Concomitant treatment with monoamine oxidase inhibitors (MAOIs), including agents with similar properties such as furazolidone and procarbazine, may provoke hypersensitivity reactions.

Patients undergoing anesthesia with halogenated hydrocarbons are at increased risk of developing arrhythmias.

Concomitant use of other beta-adrenergic or anticholinergic medicinal products may produce additive effects.

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

Hypokalemia may occur during therapy with beta2-agonists and may be potentiated by concomitant use of xanthine derivatives, corticosteroids, and diuretics (for additional information on hypokalemia, see section "Special precautions for use").

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

Paediatric populations

Drug interaction studies have been conducted only in adults.

Monoamine oxidase inhibitors and tricyclic antidepressants

Foracort®200 should be used with caution in patients taking monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks after discontinuation of such therapy, because the cardiovascular effects of formoterol (a component of Foracort®200) may be potentiated by these agents.

Diuretics

ECG changes and/or hypokalemia induced by non-potassium-sparing diuretics (such as loop or thiazide diuretics) may be acutely worsened by β-agonists, particularly if the recommended dose of β-agonists is exceeded. Although the clinical significance of these effects is not fully understood, caution is recommended when Foracort®200 is used concomitantly with non-potassium-sparing diuretics.

Special precautions for use.

To discontinue treatment, a gradual dose reduction is recommended rather than abrupt cessation of the medication.

If a patient feels that treatment is ineffective, or if the patient has reached the maximum recommended dose of Foracort®200, medical advice should be sought. Sudden or progressive exacerbation of asthma or COPD is potentially life-threatening, and the patient should undergo urgent medical evaluation. In such cases, intensified therapy should be considered, including systemic corticosteroids—for example, initiating a course of oral corticosteroids—or antibiotic treatment if infection is present.

Patients should be advised to always carry their reliever medication—either Foracort®200 (for patients with bronchial asthma using Foracort®200 for maintenance and reliever therapy) or another fast-acting bronchodilator (for all patients using Foracort®200 solely for maintenance therapy).

Patients should be reminded to take their prescribed dose of Foracort®200 regularly, even when asymptomatic. Prophylactic administration of the combination of budesonide/formoterol, for example before physical exercise, has not been studied. Inhalations of Foracort®200 for symptom relief should only be used after symptoms occur, not for regular prophylaxis, such as before physical exercise. For such purposes, short-acting bronchodilators should be used.

After achieving control of asthma symptoms, a decision may be made to gradually reduce the dose of Foracort®200. Regular monitoring of patients is essential during dose reduction. The lowest effective dose of Foracort®200 should be used.

Treatment with Foracort®200 should not be initiated during an asthma exacerbation, acute episode, or significant worsening of asthma.

Serious adverse effects related to bronchial asthma and disease exacerbations may occur during treatment with Foracort®200. Patients should be informed that they may continue treatment, but should seek medical advice if symptoms remain uncontrolled or worsen after starting Foracort®200.

There are no clinical data on the use of Foracort®200 in COPD patients with pre-bronchodilator FEV1 > 50% of predicted and post-bronchodilator FEV1 < 70% of predicted.

As with any other inhaled therapy, paradoxical bronchospasm with immediate wheezing and shortness of breath after dosing may occur. In such cases, Foracort®200 should be discontinued immediately; the treatment approach should be reassessed and alternative therapy considered. Paradoxical bronchospasm, which requires immediate treatment, responds to a short-acting inhaled bronchodilator (see section "Adverse reactions").

Systemic effects may occur with inhaled corticosteroids, especially at high doses over prolonged periods. These effects are less common with inhaled therapy than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineral density, cataract, and glaucoma. Rarely, psychiatric disturbances or behavioral changes may occur, including psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (particularly in children) (see section "Adverse reactions").

The potential impact on bone density should be particularly considered in patients receiving high doses over long periods and those with risk factors for osteoporosis. Long-term studies of inhaled budesonide at daily doses of 400 mcg (delivered dose) in children or 800 mcg (delivered dose) in adults did not show any significant effect on bone mineral density. There is no information on the effect of the budesonide/formoterol combination at higher doses.

If there is any reason to suspect adrenal suppression due to prior systemic steroid therapy, appropriate caution should be exercised when switching patients to Foracort®200.

The benefits of inhaled budesonide therapy generally minimize the need for oral steroids. However, patients previously treated with oral steroids for a prolonged period may still be at risk of adrenal suppression. Recovery after discontinuation of oral steroids may take a considerable time, so patients previously on oral steroids and switched to inhaled budesonide may remain at risk for adrenal insufficiency for a prolonged period. In such cases, the hypothalamic-pituitary-adrenal (HPA) axis function should be monitored regularly.

Prolonged treatment with high doses of inhaled corticosteroids, especially at doses higher than recommended, may also lead to clinically significant adrenal suppression. Therefore, supplemental systemic corticosteroid therapy should be considered during periods of stress (e.g., severe infections) or planned surgery. Rapid dose reduction of steroids may lead to acute adrenal crisis. Symptoms and signs observed during acute adrenal crisis may be nonspecific but 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 should not be discontinued abruptly.

When switching from oral steroid therapy to Foracort®200, the lower systemic steroid exposure may lead to the emergence of allergic symptoms or arthritis-like symptoms such as rhinitis, eczema, and muscle or joint pain. If these conditions develop, specific treatment should be initiated. Glucocorticoid insufficiency should be suspected if, rarely, 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 minimize the risk of oropharyngeal candidiasis, patients should be instructed to rinse their mouth with water after each maintenance dose. If oropharyngeal candidiasis occurs, patients should also rinse their mouth with water after inhalation.

Concomitant treatment with itraconazole, ritonavir, or other strong CYP3A4 inhibitors should be avoided (see section "Interaction with other medicinal products and other forms of interaction"). If concomitant treatment cannot be avoided, the time interval between administration of interacting drugs should be maximized. Maintenance and reliever therapy with Foracort®200 is not recommended in patients taking strong CYP3A4 inhibitors.

Caution should be exercised when administering Foracort®200 to patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic subaortic stenosis, arterial hypertension, aneurysm, and other severe cardiovascular disorders such as ischemic heart disease, tachyarrhythmia, and severe heart failure.

Caution should be exercised when treating patients with QT interval prolongation. Formoterol may itself cause QT interval prolongation.

The need for inhaled corticosteroids and their dosage should be reviewed in patients with active or latent tuberculosis, fungal infections, or viral respiratory infections.

Potentially severe hypokalemia may result from high doses of β2-agonists. Concomitant use of β2-agonists with other agents that may cause or exacerbate hypokalemia, such as xanthine derivatives, steroids, and diuretics, may increase the hypokalemic effect of β2-agonists. Particular caution should also be exercised in patients with unstable asthma using various short-acting bronchodilators, in acute asthma associated with worsening hypoxia, and in other situations with increased risk of hypokalemia-related adverse effects. In such cases, serum potassium levels should be monitored.

For all β2-agonists, additional monitoring of blood glucose levels is recommended in patients with diabetes mellitus.

Pneumonia and other lower respiratory tract infections

Physicians should remain vigilant for the possible development of pneumonia in COPD patients, due to the frequent overlap of clinical signs of pneumonia and exacerbation of the underlying disease. Lower respiratory tract infections, including pneumonia, have been observed following inhaled corticosteroid use.

Immunosuppression

Patients receiving medications that suppress the immune system are more susceptible to infections than healthy individuals.

Pneumonia in COPD patients

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 is no convincing clinical evidence of differences between inhaled corticosteroid products in the magnitude of pneumonia risk.

Physicians should be cautious regarding the possible development of pneumonia in COPD patients, as clinical signs of such infections may mimic symptoms of COPD exacerbation.

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

Paediatric populations

Regular monitoring of growth in children receiving long-term inhaled corticosteroid therapy is recommended. If growth is slowed, therapy should be reviewed with the aim of reducing the inhaled corticosteroid dose. The benefits of corticosteroid therapy and the potential risks of growth suppression should be carefully weighed. Additionally, consultation with a pediatric respiratory specialist is recommended.

Limited long-term data indicate that most children receiving inhaled budesonide eventually achieve their expected adult height. However, an initial, albeit transient, reduction in growth velocity (approximately 1 cm) has been observed, typically during the first year of treatment.

Use during pregnancy or breastfeeding.

Pregnancy

There are no clinical data on the effects of the budesonide/formoterol combination or concomitant treatment with formoterol and budesonide during pregnancy. Animal studies on the effects of this combination on embryofetal development did not reveal any additional adverse effects when used in combination.

There are insufficient data on the use of formoterol in pregnant women. Animal reproductive studies have shown adverse effects with formoterol at very high systemic doses.

No increased teratogenic risk associated with inhaled budesonide has been demonstrated in human studies. Animal studies have shown that glucocorticoids may cause developmental abnormalities; however, these findings are likely not relevant to humans when the drug is used at recommended doses.

Available animal studies indicate that high-dose glucocorticoid use during pregnancy increases the risk of intrauterine growth retardation, cardiovascular disease in adult offspring, and permanent changes in glucocorticoid receptor density, metabolism, and neurotransmitter profiles, even at doses below teratogenic levels.

Foracort®200 should be used during pregnancy only if the potential benefit to the mother outweighs any potential risk to the fetus or child. The lowest effective dose of budesonide necessary to maintain adequate asthma control should be prescribed.

Breastfeeding

Budesonide is excreted in breast milk. However, no adverse effects on breastfed infants have been observed at therapeutic doses. There are no data on whether formoterol is excreted in breast milk. Foracort®200 should be prescribed to breastfeeding women 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. Animal studies on the effects of formoterol on reproductive function showed a slightly reduced fertility in male animals at high systemic exposure.

Ability to affect reaction speed when driving or operating machinery.

Foracort®200 has no effect or only a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Bronchial Asthma

The drug is not intended for initial treatment of bronchial asthma. Dosage is individual and adjusted according to disease severity. This should be taken into account not only at the beginning of using 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 beta2-agonists and/or corticosteroids should be prescribed using separate inhalers.

Dosage should be titrated to the lowest effective dose for controlling symptoms. Patients must undergo regular follow-up examinations by the physician who prescribed the drug to ensure the dosage remains optimal. After achieving long-term symptom control with the lowest recommended dose, an attempt should be made to control symptoms using only an inhaled corticosteroid.

There are two regimens for using the drug:

А. For maintenance therapy.

Formoterol®200 is used regularly for maintenance therapy, while symptoms are relieved using a separate short-acting bronchodilator as a rescue medication.

Б. For maintenance and reliever therapy.

Formoterol®200 is used regularly for maintenance therapy and, as needed, for symptom relief.

Use of Formoterol®200 for maintenance therapy.

Patients should be advised to always carry a separate short-acting bronchodilator as a rescue medication.

Recommended doses

Adults: 1–2 inhalations twice daily. Some patients may require up to 4 inhalations twice daily.

Children aged 12 to 18 years: 1–2 inhalations twice daily.

Typically, after achieving symptom control with twice-daily dosing, the dose should be titrated down to the lowest effective dose, including reducing to Formoterol®200 once daily, in cases where, in the physician’s opinion, the patient 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.

Use of Formoterol®200 for maintenance and reliever therapy.

Patients should take the daily maintenance dose of Formoterol®200 and, additionally, use Formoterol®200 as needed for symptom relief. Patients should be advised to always carry Formoterol®200 as a rescue medication.

The use of Formoterol®200 for maintenance and reliever therapy 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 extensively use Formoterol®200 should be closely monitored for the development of dose-dependent adverse effects.

Recommended doses

Adults and children aged 12 years and older: the recommended maintenance dose is 2 inhalations daily: one in the morning and one in the evening, or 2 inhalations either in the morning or in the evening. Some patients may be prescribed a maintenance dose of 2 inhalations twice daily. As needed, one additional inhalation should be taken when symptoms occur. If symptoms persist after several minutes, another additional inhalation may be administered. No more than 6 inhalations should be taken at one time.

The total daily dose should not exceed 8 inhalations, although during short periods the total daily dose may reach up to 12 inhalations. Patients using more than 8 inhalations per day should consult their physician. They should undergo reassessment and review of maintenance therapy.

Children under 12 years of age: Formoterol®200 is not recommended for maintenance and reliever therapy in children under 12 years of age.

Chronic Obstructive Pulmonary Disease (COPD)

Recommended dose

Adults: 2 inhalations twice daily.

General Information

Special patient groups

No special dosage requirements are necessary for elderly patients. Data on the use of Formoterol®200 in patients with impaired renal or hepatic function are lacking. Since budesonide and formoterol are primarily eliminated via hepatic metabolism, increased systemic exposure to the drug may be expected in patients with severe hepatic cirrhosis.

Instructions for Inhaler Use

Checking the inhaler

Before the first use of the inhaler or after a break in use exceeding one week, remove the mouthpiece cap by gently pressing its sides, shake the inhaler well, and release one spray into the air to ensure proper function.

Using the inhaler

1. Remove the mouthpiece cap by gently pressing its sides.
2. Ensure that the inside and outside of the inhaler, including the mouthpiece, are free of foreign objects.
3. Shake the inhaler thoroughly to dislodge any foreign objects and to ensure uniform mixing of its contents.
4. Hold the inhaler vertically in the hand between the thumb and other fingers, with the thumb placed on the inhaler body below the mouthpiece and the index finger on the top of the inhaler.
5. Breathe out fully, then place the mouthpiece in the mouth between the teeth and seal lips around it without biting.
6. While inhaling slowly and deeply through the mouth, press down on the top of the inhaler to release the medication, continuing to inhale slowly and deeply. One press of the inhaler delivers one dose.
7. Hold breath, remove the inhaler from the mouth, and release the finger from the top of the inhaler. Continue holding breath as long as possible.
8. If a second spray is needed, wait approximately 30 seconds while holding the inhaler vertically, then repeat steps 3–7.
9. Replace the mouthpiece cap by pressing it into place until a click is heard.

Children. Children are advised to learn the inhalation technique under adult supervision. Children or weakened adults may hold the inhaler with both hands. Place both index fingers on the top of the inhaler and both thumbs on the base below the mouthpiece.

Adults may administer inhalations to children. Ask the child to exhale and administer the spray immediately after the child begins to inhale.

Important to note!

Steps 5, 6, and 7 should be performed without rushing.

Inhalation immediately before spraying should be as slow as possible. The first few times, practice in front of a mirror.

If a "mist" appears at the top of the inhaler or around the corners of the mouth, restart the procedure from step 2.

Immediately after use, cover the mouthpiece with the cap by pressing gently until a click is heard.

As with other inhaled medications, therapeutic effectiveness may be reduced if the canister becomes cold.

Do not immerse the metal canister in water.

Do not disassemble, puncture, or burn the canister, even after complete use.

Recommendations for cleaning the inhaler

The inhaler should be cleaned at least once a week.

1. Carefully remove the metal canister from the plastic inhaler adapter. Remove the mouthpiece cap.
2. Rinse the adapter and mouthpiece cap with warm water. Do not immerse the metal canister in water!
3. Shake excess water from the adapter and mouthpiece cap and leave them to dry on a clean towel in a warm place. Avoid excessive heat.
4. Carefully reinsert the metal canister and replace the mouthpiece cap.

Children.

Formoterol®200 is not recommended for use in children under 12 years of age.

Overdose.

Overdose of formoterol is most likely to cause reactions typical of β2-adrenergic receptor agonists: tremor, headache, and tachycardia. In isolated cases, tachycardia, hyperglycemia, hypokalemia, prolonged QT interval, arrhythmia, nausea, and vomiting have been observed. Supportive and symptomatic treatment may be administered. A dose of 90 mcg administered over three hours in patients with acute bronchial obstruction does not require special safety measures.

Acute overdose of budesonide, even in large doses, is not expected to cause clinically significant symptoms. However, prolonged use of excessive doses may result in systemic glucocorticoid effects such as hypercorticism and adrenal suppression.

If treatment with Formoterol®200 is discontinued due to formoterol overdose (a component of the drug), appropriate therapy with inhaled corticosteroids should be initiated.

Adverse reactions

Since Foracort®200 contains both budesonide and formoterol, it may cause the same adverse effects observed with the use of each compound separately. An increased incidence of adverse effects with concomitant administration of these two components has not been observed. The most commonly reported adverse effects associated with the use of this medication are pharmacologically predictable side effects of β2-agonist therapy, such as tremor and tachycardia. These reactions are usually mild and tend to disappear after a few days of treatment.

Adverse events reported in clinical studies of the budesonide/formoterol combination are listed below by system organ class and frequency of occurrence. The frequencies are defined as follows: very common (> 1/10), common (> 1/100 and < 1/10), uncommon (> 1/1,000 and < 1/100), rare (> 1/10,000 and < 1/1,000), and very rare (< 1/10,000).

Cardiac and vascular system	common	Pounding heartbeat
	uncommon	Tachycardia
	rare	Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles
	very rare	Angina pectoris, QT interval prolongation, changes in blood pressure
Endocrine system	very rare	Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density
Eye disorders	very rare	Cataract and glaucoma
Gastrointestinal disorders	uncommon	Nausea
Immune system disorders	rare	Immediate or delayed hypersensitivity reactions, e.g. exanthema, urticaria, pruritus, dermatitis, angioneurotic edema, and anaphylactic reactions
Infections and infestations	common	Oral and pharyngeal candidiasis Pneumonia (in patients with COPD)
Nutritional and metabolism disorders	rare	Hypokalemia
	very rare	Hyperglycemia
Musculoskeletal and connective tissue disorders	uncommon	Muscle cramps
Nervous system disorders	common	Headache, tremor
	uncommon	Dizziness
	very rare	Taste disturbance
Psychiatric disorders	uncommon	Aggression, psychomotor hyperactivity, anxiety, sleep disturbances
	very rare	Depression, behavioral disturbances (mainly in children)
Respiratory system disorders	common	Mild irritation in the throat, cough, hoarseness
	rare	Bronchospasm
Skin and subcutaneous tissue disorders	uncommon	Contusions

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

As with any other inhaled therapy, paradoxical bronchospasm, characterized by immediate increase in wheezing and onset of dyspnea following drug administration, may very rarely occur (less than 1 case per 10,000 patients). Paradoxical bronchospasm, which should be treated immediately, responds to administration of a fast-acting inhaled bronchodilator. In such cases, the drug should be discontinued immediately, the patient's condition should be evaluated, and alternative therapy should be initiated if necessary (see section "Special precautions for use").

Systemic effects may occur with inhaled corticosteroids, particularly at high doses and during prolonged treatment. The likelihood of such effects is lower with inhaled corticosteroids compared to oral formulations. Possible systemic effects include Cushing's syndrome, Cushingoid features, 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 be observed. These effects are likely dose- and exposure duration-dependent, and may also be influenced by concomitant or prior steroid use and individual sensitivity.

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

The use of systemic and inhaled corticosteroids may lead to pneumonia or lower respiratory tract infections in patients with COPD and immunosuppression.

Paediatric populations

Regular monitoring of growth in children receiving long-term inhaled corticosteroids is recommended (see section "Special precautions for use").

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after registration of the medicinal product is important. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions.

Shelf life. 3 years.

Storage conditions.

Store below 30 °C in a place inaccessible to children. Protect from direct sunlight. Do not freeze.

Packaging.

120 doses in an aluminum pressurized container with a metering valve. Each container is equipped with a polypropylene actuator and a protective cap. One container per cardboard box, enclosed in a transparent plastic overwrap with a tamper-evident tear-off strip.

Prescription status.

Prescription only.

Manufacturer. Medispray Laboratories Pvt. Ltd.

Manufacturer's address and place of business.

344/345 Kundra Industrial Estate, Kundra, Goa, IN-403 115, India.