Neumoterol

Budesonide, formoterol fumarate dihydrate.

Hard and colorless capsule containing white colored powder.
One hard capsule of Budesonide + Formoterol (Neumoterol) contains 200 mcg of Budesonide and 6 mcg of Formoterol dihydrate or 400 mcg of Budesonide and 12 mcg of Formoterol fumarate dihydrate (Formoterol fumarate dihydrate is hereafter referred to as "formoterol").
Excipients/Inactive Ingredients: Lactose monohydrate which contains milk proteins.

Pharmacotherapeutic group: Adrenergics and drugs for obstructive airway diseases. ATC code: R03AK07.
Pharmacology: Pharmacodynamics: Mechanisms of action and Pharmacodynamic effects: Neumoterol contains formoterol and budesonide, which have different modes of action and show additive effects in terms of reduction of asthma exacerbations. The mechanism of action of the two substances, respectively are discussed as follows.
Budesonide: Budesonide is a glucocorticoid which when inhaled has a dose-dependent anti-inflammatory action in the airways, resulting in reduced symptoms and fewer exacerbations of asthma. Inhaled budesonide has less severe adverse effects than systemic corticosteroids. The exact mechanism responsible for the anti-inflammatory effect of the glucocorticoids is unknown.
Formoterol: Formoterol is a selective beta₂-adrenoceptor agonist that when inhaled results in rapid and long-acting relaxation of bronchial smooth muscle in patients with reversible obstruction of the airways. The bronchodilator effect is dose-dependent, with an onset of effect within 1-3 minutes. The duration of effect is at least 12 hours after a single dose.
Clinical efficacy and safety: Asthma: Clinical studies in adults have shown that the addition of formoterol to budesonide improved asthma symptoms and lung function, and reduced exacerbations. In two 12-week studies, the effect on lung function of budesonide/formoterol was equal to that of the free combination of budesonide and formoterol, and exceeded that of budesonide alone. All treatment arms used a short-acting β₂-adrenoceptor agonist as needed. There was no sign of attenuation of the anti-asthmatic effect over time.
Two 12-week paediatric studies have been performed in which 265 children aged 6-11 years were treated with a maintenance dose of budesonide/formoterol (2 inhalations of 80 micrograms /4.5 micrograms/inhalation twice daily), and a short acting β₂-adrenoceptor agonist as needed. In both studies, lung function was improved and the treatment was well tolerated compared to the corresponding dose of budesonide alone.
Clinical efficacy for budesonide/formoterol maintenance and reliever therapy: A total of 12,076 asthma patients were included in 5 double-blind efficacy and safety studies (4,447 were randomised to budesonide/formoterol maintenance and reliever therapy) for 6 or 12 months. Patients were required to be symptomatic despite use of inhaled glucocorticosteroids.
Budesonide/formoterol maintenance and reliever therapy provided statistically significant and clinically meaningful reductions in severe exacerbations for all comparisons in all 5 studies. This included a comparison with budesonide/formoterol at a higher maintenance dose with terbutaline as reliever (study 735) and budesonide/formoterol at the same maintenance dose with either formoterol or terbutaline as reliever (study 734) (Table 1). In Study 735, lung function, symptom control, and reliever use were similar in all treatment groups.
In Study 734, symptoms and reliever use were reduced and lung function improved, compared with both comparator treatments. In the 5 studies combined, patients receiving budesonide/formoterol maintenance and reliever therapy used, on average, no reliever inhalations on 57% of treatment days. There was no sign of development of tolerance over time. (See Table 1.)

Click on icon to see table/diagram/image

In 2 other studies with patients seeking medical attention due to acute asthma symptoms, budesonide/formoterol provided rapid and effective relief of bronchoconstriction similar to salbutamol and formoterol.
Pharmacokinetics: Absorption: The fixed-dose combination of budesonide and formoterol and the corresponding monoproducts have been shown to be bioequivalent with regard to systemic exposure of budesonide and formoterol, respectively. In spite of this, a small increase in cortisol suppression was seen after administration of the fixed-dose combination compared with the monoproducts. The difference is considered not to have an impact on clinical safety. There was no evidence of pharmacokinetic interactions between budesonide and formoterol.
Pharmacokinetic parameters for the respective substances were comparable after the administration of budesonide and formoterol as monoproducts or as the fixed-dose combination. For budesonide, AUC was slightly higher, rate of absorption more rapid and maximal plasma concentration higher after administration of the fixed combination. For formoterol, maximal plasma concentration was similar after administration of the fixed combination. Inhaled budesonide is rapidly absorbed and the maximum plasma concentration is reached within 30 minutes after inhalation. In studies, mean lung deposition of budesonide after inhalation via the powder inhaler ranged from 32% to 44% of the delivered dose. The systemic bioavailability is approximately 49% of the delivered dose. In children 6-16 years of age the lung deposition falls in the same range as in adults for the same given dose. The resulting plasma concentrations were not determined.
Inhaled formoterol is rapidly absorbed and the maximum plasma concentration is reached within 10 minutes after inhalation. In studies the mean lung deposition of formoterol after inhalation via the powder inhaler ranged from 28% to 49% of the delivered dose. The systemic bioavailability is about 61% of the delivered dose.
Distribution and biotransformation: Plasma protein binding is approximately 50% for formoterol and 90% for budesonide. Volume of distribution is about 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 seen mainly as inactivated conjugates). Budesonide undergoes an extensive degree (approximately 90%) of biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and 16-alfa-hydroxy-prednisolone, is less than 1% of that of budesonide. There are no indications of any metabolic interactions or any displacement reactions between formoterol and budesonide.
Elimination: The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination. After inhalation, 8% to 13% of the delivered dose of formoterol is excreted unmetabolised in the 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 mainly catalysed by the enzyme CYP3A4. The metabolites of budesonide are eliminated in urine as such or in conjugated form. Only negligible amounts of unchanged budesonide have been detected in the urine.
Budesonide has a high systemic clearance (approximately 1.2 l/min) and the plasma elimination half-life after i.v. dosing averages 4 hours.
The pharmacokinetics of budesonide or formoterol in children and patients with renal failure are unknown. The exposure of budesonide and formoterol may be increased in patents with liver disease.
Linearity/Non-linearity: Systemic exposure for both budesonide and formoterol correlates in a linear fashion to administered dose.
Toxicology: Preclinical safety data: The toxicity observed in animal studies with budesonide and formoterol, given in combination or separately, were effects associated with exaggerated pharmacological activity. In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). However, these animal experimental results do not seem to be relevant in humans at the recommended doses. Animal reproduction studies with formoterol have shown a somewhat reduced fertility in male rats at high systemic exposure and implantation losses as well as decreased early postnatal survival and birth weight at considerably higher systemic exposures than those reached during clinical use. However, these animal experimental results do not seem to be relevant in humans.

Budesonide + Formoterol (Neumoterol) is indicated in adults, and adolescents aged 12-17 years, for the regular treatment of asthma where use of a combination (inhaled corticosteroid and a long-acting beta₂ adrenoceptor agonist) is appropriate: Patients not adequately controlled with inhaled corticosteroids and "as needed" inhaled short-acting beta₂ adrenoceptor agonists, or Patients already adequately controlled with both inhaled corticosteroids and long-acting beta₂-adrenoceplor agonists.

Route of administration: For inhalation use.
Dosage: Budesonide + Formoterol (Neumoterol) is not intended for the initial management of asthma. The dosage of the components of Budesonide + Formoterol (Neumoterol) is individual and should be adjusted to the severity of the disease. This should be considered not only when treatment with combination products is initiated but also when the maintenance dose is adjusted. If an individual patient should require a combination of doses other than those available in the combination inhaler, appropriate doses of β₂ adrenoceptor agonists and/or corticosteroids by individual inhalers should be prescribed.
The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Patients should be regularly reassessed by their prescriber/health care provider so that the dosage of Budesonide + Formoterol (Neumoterol) remains optimal. When long-term control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid alone.
For Budesonide + Formoterol (Neumoterol) there are two treatment approaches: Budesonide + Formoterol (Neumoterol) maintenance therapy: Budesonide + Formoterol (Neumoterol) is taken as regular maintenance treatment with a separate rapid-acting bronchodilator as rescue.
Patients should be advised to have their separate rapid-acting bronchodilator available for rescue use at all times.
Recommended doses: Adults (18 years and older): 1-2 inhalations twice daily. Some patients may require up to a maximum of 4 inhalations twice daily.
Adolescents (12-17 years): 1-2 inhalations twice daily.
In usual practice when control of symptoms is achieved with the twice daily regimen, titration to the lowest effective dose could include Neumoterol given once daily, when in the opinion of the prescriber, a long-acting bronchodilator would be required to maintain control.
Increasing use of a separate rapid acting bronchodilator indicates a worsening of the underlying condition and warrants a reassessment of the asthma therapy.
Children under 12 years: As only limited data are available, Budesonide + Formoterol (Neumoterol) is not recommended for children younger than 12 years.
Budesonide + Formoterol (Neumoterol) maintenance and reliever therapy: Budesonide + Formoterol (Neumoterol) is taken as regular maintenance treatment and as needed in response to symptoms.
Patients take a daily maintenance dose of Budesonide + Formoterol (Neumoterol) and in addition take Budesonide + Formoterol (Neumoterol) as needed in response to symptoms. Patients should be advised to always have Budesonide + Formoterol (Neumoterol) available for rescue use.
Budesonide + Formoterol (Neumoterol) maintenance and reliever therapy should especially be considered for patients with: inadequate asthma control and in frequent need of reliever medication; asthma exacerbations in the past requiring medical intervention.
Close monitoring for dose-related adverse effects is needed in patients who frequently take high numbers of Budesonide + Formoterol (Neumoterol) as-needed inhalations.
Recommended doses: Adults (18 years and older): The recommended maintenance dose is 2 inhalations per day, given either as one inhalation in the morning and evening or as 2 inhalations in either the morning or evening. Patients should take 1 additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion.
A total daily dose of more than 8 inhalations is not normally needed; however, a total daily dose of up to 12 inhalations could be used for a limited period. Patients using more than 8 inhalations daily should be strongly recommended to seek medical advice. They should be reassessed and their maintenance therapy should be reconsidered.
Children and adolescents under 18 years: Budesonide + Formoterol (Neumoterol) maintenance and reliever therapy is not recommended for children and adolescents.
General Information: Special patient groups: There are no special dosing requirements for elderly patients. There are no data available for use of Budesonide + Formoterol (Neumoterol) in patients with hepatic or renal impairment. As budesonide and formoterol are primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe liver cirrhosis.
Method of administration: Instructions for correct use of Budesonide + Formoterol (Neumoterol): Patients should be instructed to use Budesonide + Formoterol (Neumoterol) even when they are asymptomatic in order to get the maximum benefit from therapy.
Follow the instructions under Patient Counselling Information to learn how to use Budesonide + Formoterol (Neumoterol) with the inhaler. The budesonide and formoterol capsules must be used only with the inhaler provided in the package. This inhaler was created especially for use with the budesonide and formoterol capsules.
The capsules should only be removed from the bottle and handled immediately prior to use, so that they do not suffer any effects of moisture from hands or the environment.
Make sure that the hands are completely dry so that the capsule does not get wet.
Warning: Do not swallow the capsules. Use the powder of the capsule only for inhalation.

An overdose of formoterol would likely lead to effects that are typical for beta₂-adrenoceptor agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc interval, arrhythmia, nausea and vomiting. Supportive and symptomatic treatment may be indicated. A dose of 90 micrograms administered during three hours in patients with acute bronchial obstruction raised no safety concerns.
Acute overdosage with budesonide, even in excessive doses, is not expected to be a clinical problem. When used chronically in excessive doses, chronic systemic glucocorticoid effects, such as hypercorticism and adrenal suppression may appear.
If Neumoterol therapy has to be withdrawn due to overdose of the formoterol component of the drug, provision of appropriate inhaled corticosteroid therapy must be considered.

Hypersensitivity to the active substance(s) or to any of the excipients listed in Description.

It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped abruptly.
If patients find the treatment ineffective, or exceed the highest recommended dose of Neumoterol, medical attention must be sought (see Dosage & Administration). Sudden and progressive deterioration in control of asthma is potentially life threatening and the patient should undergo urgent medical assessment. In this situation consideration should be given to the need for increased therapy with corticosteroids e.g. a course of oral corticosteroids, or antibiotic treatment if an infection is present.
Patients should be advised to have their rescue inhaler available at all times, either Neumoterol (for patients using Neumoterol as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for patients using Neumoterol as maintenance therapy only).
Patients should be reminded to take their Neumoterol maintenance dose as prescribed, even when asymptomatic.
The prophylactic use of Neumoterol, e.g. before exercise, has not been studied. The reliever inhalations of Neumoterol should be taken in response to asthma symptoms but are not intended for regular prophylactic use, e.g. before exercise. For such use, a separate rapid-acting bronchodilator should be considered.
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Neumoterol. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Neumoterol should be used (see Dosage & Administration).
Patients should not be initiated on Neumoterol during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma.
Serious asthma-related adverse events and exacerbations may occur during treatment with Neumoterol. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Neumoterol.
As with other inhalation therapy, paradoxical bronchospasm may occur, with an immediate increase in wheezing and shortness of breath after dosing. If the patient experiences paradoxical bronchospasm Neumoterol should be discontinued immediately, the patient should be assessed and an alternative therapy instituted if necessary. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway (see Adverse Reactions).
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur with inhalation treatment than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children) (see Adverse Reactions).
Long-term studies with inhaled budesonide in children at mean daily doses of 400 micrograms (metered dose) or in adults at daily doses of 800 micrograms (metered dose) have not shown any significant effects on bone mineral density. No information regarding the effect of Neumoterol at higher doses is available.
If there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy, care should be taken when transferring patients to Neumoterol therapy.
The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients transferring from oral steroids may remain at risk of impaired adrenal reserve fora considerable time. Recovery may take a considerable amount of time after cessation of oral steroid therapy and hence oral steroid-dependent patients transferred to inhaled budesonide may remain at risk from impaired adrenal function for some considerable time. In such circumstances HPA axis function should be monitored regularly. Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than recommended doses, may also result in clinically significant adrenal suppression. Therefore additional systemic corticosteroid cover should be considered during periods of stress such as severe infections or elective surgery. Rapid reduction in the dose of steroids can induce acute adrenal crisis. Symptoms and signs which might be seen in acute adrenal crisis may be somewhat vague but may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension and hypoglycaemia.
Treatment with supplementary systemic steroids or inhaled budesonide should not be stopped abruptly.
During transfer from oral therapy to Neumoterol Turbohaler, a generally lower systemic steroid action will be experienced which may result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment should be initiated for these conditions. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is sometimes necessary.
To minimise the risk of oropharyngeal candida infection (see Adverse Reactions), the patient should be instructed to rinse their mouth out with water after inhaling the maintenance dose. If oropharyngeal thrush occurs, patients should also rinse their mouth with water after the as-needed inhalations.
Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 inhibitors should be avoided (see Interactions). If this is not possible the time interval between administration of the interacting drugs should be as long as possible. In patients using potent CYP3A4 inhibitors, Neumoterol maintenance and reliever therapy is not recommended.
Neumoterol should be administered with caution in patients with thyrotoxicosis, phaeochromocytoma, diabetes mellitus, untreated hypokalaemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.
Caution should be observed when treating patients with prolongation of the QTc-interval. Formoterol itself may induce prolongation of the QTc-interval.
The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent pulmonary tuberculosis, fungal and viral infections in the airways. Potentially serious hypokalaemia may result from high doses of β₂-adrenoceptor agonists. Concomitant treatment of β₂-adrenoceptor agonists with drugs which can induce hypokalaemia or potentiate a hypokalaemic effect, e.g. xanthine-derivatives, steroids and diuretics, may add to a possible hypokalaemic effect of the β₂-adrenoreceptor agonist. Particular caution is recommended in unstable asthma with variable use of rescue bronchodilators, in acute severe asthma as the associated risk may be augmented by hypoxia and in other conditions when the likelihood for hypokalaemia is increased. It is recommended that serum potassium levels are monitored during these circumstances.
As for all β₂-adrenoreceptor agonists, additional blood glucose controls should be considered in diabetic patients.
Neumoterol contains lactose in low concentration which generally does not cause problems for lactose-intolerant people. The excipient lactose contains small amounts of milk proteins, which may cause allergic reactions.
Effects on ability to drive and use machines: Neumoterol has no or negligible influence on the ability to drive and use machines.
Use in Children: It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained, if possible.
The benefits of the corticosteroid therapy and the possible risks of growth suppression must be carefully weighed. In addition consideration should be given to referring the patient to a paediatric respiratory specialist.
Limited data from long-term studies suggest that most children and adolescents treated with inhaled budesonide will ultimately achieve their adult target height. However, an initial small but transient reduction in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment.

Pregnancy: For Neumoterol or the concomitant treatment with formoterol and budesonide, no clinical data on exposed pregnancies are available. Data from an embryo-fetal development study in the rat showed no evidence of any additional effect from the combination.
There are no adequate data from use of formoterol in pregnant women. In animal studies formoterol has caused adverse effects in reproduction studies at very high systemic exposure levels (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
Data on approximately 2,000 exposed pregnancies indicate no increased teratogenic risk associated with the use of inhaled budesonide. In animal studies glucocorticosteroids have been shown to induce malformations (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). This is not likely to be relevant for humans given recommended doses.
Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.
During pregnancy, Neumoterol should only be used when the benefits outweigh the potential risks. The lowest effective dose of budesonide needed to maintain adequate asthma control should be used.
Breast-feeding: Budesonide is excreted in breast milk. However, at therapeutic doses no effects on the suckling child are anticipated. It is not known whether formoterol passes into human breast milk. In rats, small amounts of formoterol have been detected in maternal milk. Administration of Neumoterol to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.
Fertility: There is no data available on the potential effect of budesonide on fertility. Animal reproduction studies with formoterol have shown a somewhat reduced fertility in male rats at high systemic exposure (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).

Since Neumoterol contains budesonide and formoterol, the same pattern of undesirable effects as reported for these substances may occur. No increased incidence of adverse reactions has been seen following concurrent administration of the two compounds. The most common drug related adverse reactions are pharmacologically predictable side-effects of beta₂-agonist treatment, such as tremors and palpitations. These tend to be mild and usually disappear after a few days of treatment.
Adverse reactions, which have been associated with budesonide or formoterol, are given as follows, listed by system organ class and frequency. Frequencies are defined as: 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) and very rare (<1/10,000). (See Table 2.)

Click on icon to see table/diagram/image

Candida infection in the oropharynx is due to drug deposition. Advising the patient to rinse the mouth out with water after each maintenance dose will minimise the risk. Oropharyngeal Candida infection usually responds to topical anti-fungal treatment without the need to discontinue the inhaled corticosteroid. If oropharyngeal thrush occurs, patients should also rinse their mouth with water after the as-needed inhalations.
As with other inhalation therapy, paradoxical bronchospasm may occur very rarely, affecting less than 1 in 10,000 people, with an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway.
Neumoterol should be discontinued immediately, the patient should be assessed and an alternative therapy instituted if necessary (see Precautions).
Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. Increased susceptibility to infections and impairment of the ability to adapt to stress may also occur. Effects are probably dependent on dose, exposure time, concomitant and previous steroid exposure and individual sensitivity.
Treatment with β₂ agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.
Paediatric population: It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored (see Precautions).

Pharmacokinetic interactions: Potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors) are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided. If this is not possible the time interval between administration of the inhibitor and budesonide should be as long as possible (see Precautions).
In patients using potent CYP3A4 inhibitors, Neumoterol maintenance and reliever therapy is not recommended.
The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased plasma levels of concomitantly orally administered budesonide (single dose of 3 mg) on average sixfold. When ketoconazole was administered 12 hours after budesonide the concentration was on average increased only three-fold showing that separation of the administration times can reduce the increase in plasma levels. Limited data about this interaction for high-dose inhaled budesonide indicates that marked increases in plasma levels (on average four fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled budesonide (single dose of 1,000 μg).
Pharmacodynamic interactions: Beta-adrenergic blockers can weaken or inhibit the effect of formoterol. Neumoterol should therefore not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons. Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine) and tricyclic antidepressants can prolong the QTc-interval and increase the risk of ventricular arrhythrnias.
In addition L-Dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards β₂-sympathomimetics.
Concomitant treatment with monoamine oxidase inhibitors, including agents with similar properties such as furazolidone and procarbazine, may precipitate hypertensive reactions. There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.
Concomitant use of other beta-adrenergic drugs or anticholinergic drugs can have a potentially additive bronchodilating effect.
Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.
Budesonide and formoterol have not been observed to interact with any other drugs used in the treatment of asthma.
Paediatric population: Interaction studies have only been performed in adults.

Incompatibilities: Not applicable.

Store at temperature not exceeding 30°C. Store in the original package in order to protect from moisture.

Directions for use: 1. Remove the cover.
2. Firmly grasp the base of the inhaler and, to open it, turn the mouthpiece in counterclockwise direction.
3. Remove the capsule from the bottle and put it in the internal compartment in the base of the inhaler. It is important that the capsule is only removed from the bottle immediately before using the inhaler.
4. Turn the mouthpiece to the closed position.
5. Press the buttons completely only once, holding the inhaler upright. Release the buttons.
6. Release as much air from your lungs as possible.
7. Place the mouthpiece of the inhaler in your mouth and close your lips around it. Tilt you head slightly down (approximately 45°). Inhale quickly and as deeply as possible. You should hear a vibration as the capsule spins in the internal compartment dispersing the medicinal product.
Note: If you do not hear the sound of the capsule spinning, it may be stuck; in this case, open the internal compartment again, detach the capsule and repeat the procedure.
8. Hold your breath while counting in your head to 10 (about 10 seconds); remove the inhaler from your mouth, then breathe normally. Open the inhaler and see if there is still powder residue in the capsule. If there is still powder, repeat steps 4 to 8.
9. After use, open the inhaler, remove and discard the empty capsule. Close the mouthpiece and put the cover back.
Important: Wash your mouth with water and/or brush your teeth immediately after using the medicinal product.
Cleaning: Once per week, you should clean the outside of the mouthpiece with a dry cloth. Never wash the inhaler, since its contents are sensitive to moisture. Never lend you inhaler to another person.

Antiasthmatic & COPD Preparations

R03AK07 - formoterol and budesonide ; Belongs to the class of adrenergics in combination with corticosteroids or other drugs, excluding anticholinergics. Used in the treatment of obstructive airway diseases.

Rx