- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyThe therapeutic effect begins after a few days´ treatment and reaches its maximum after some weeks of treatment.When transferring a patient to Easyhaler Budesonide from other inhalation devices, the treatment should be individualised. The previous active substance, dose regimen, and method of delivery should be considered. The patients should be prescribed a starting dose of inhaled budesonide which is appropriate for the severity or level of control of their disease. The dose should be adjusted until control is achieved and then titrated to the lowest dose at which effective control of asthma is maintained. Lower strengths of Easyhaler Budesonide are available for appropriate dose adjustment, if necessary.The starting dose for adults (including the elderly and adolescents 12 to 17 years) with mild asthma (Step 2) and for children 6 to 11 years of age is 200-400 micrograms/day. If needed, the dose can be increased up to 800 micrograms/day. For adult patients with moderate (Step 3) and severe (Step 4) asthma the starting dose can be up to 1600 micrograms/day. The maintenance dose should be adjusted to meet the requirements of an individual patient taking into account the severity of the disease and the clinical response of the patient.
Twice daily dosingAdults with mild, moderate or severe asthma (including the elderly and adolescents 12 to 17 years): The usual maintenance dose is 100-400 micrograms twice daily. During periods of severe asthma, the daily dose may be increased up to 1600 micrograms administered in divided (two) doses and subsequently reduced when asthma has stabilised.Children 6 to 11 years: The usual maintenance dose is 100-200 micrograms twice daily. If needed, the daily dose may be increased up to 800 micrograms administered in divided (two) doses and subsequently reduced when asthma has stabilised.
Once daily dosingAdults with mild to moderate asthma (including the elderly and adolescents 12 to 17 years): In patients who have not previously received inhaled corticosteroids the usual maintenance dose is 200-400 micrograms once daily. In patients already controlled on inhaled corticosteroids (eg budesonide or beclometasone dipropionate) administered twice daily, once daily dosing up to 800 micrograms may be used.Children 6 to 11 years with mild to moderate asthma: In steroid naive patients or patients controlled on inhaled corticosteroids (eg budesonide or beclometasone dipropionate) administered twice daily the usual maintenance dose is 200-400 micrograms once daily.The patient should be transferred to once daily dosing at the same equivalent total daily dose (with consideration of the drug and the method of delivery). The dose should be subsequently reduced to the minimum needed to maintain good asthma control. Patients should be instructed to take the once daily dose in the evening. It is important that the dose is taken consistently and at the same time each evening. There are insufficient data to make recommendations for the transfer of patients from newer inhaled corticosteroids to once daily Easyhaler Budesonide.Patients, in particular those receiving once daily treatment, should be advised that if their asthma deteriorates (e.g. increased frequency of bronchodilator use or persistent respiratory symptoms) they should double their corticosteroid dose by administering twice daily. They should be advised to contact their doctor as soon as possible.A rapid-acting inhaled bronchodilator should be available for the relief of acute symptoms of asthma at all times.
Patients maintained on oral glucocorticosteroidsThe transfer of patients treated with oral corticosteroids to the inhaled corticosteroid and their subsequent management requires special care. The patients should be in a reasonably stable state before initiating a high dose of inhaled corticosteroid through twice daily dosing in addition to their usual maintenance dose of systemic corticosteroid. After about 10 days, withdrawal of the systemic corticosteroid is started by reducing the daily dose gradually (by for example 2.5 milligrams prednisolone or the equivalent each month) to the lowest possible level. It may be possible to completely replace the oral corticosteroid with inhaled corticosteroid
Method of administrationFor inhalation use. For optimum response, Easyhaler Budesonide inhalation powder should be used regularly. Instructions for use and handling It should be ensured that the patient is instructed in the use of the inhaler by a doctor or pharmacist.Easyhaler is an inspiratory flow-driven device. This means that when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airways.Note: It is important to instruct the patient- To carefully read the instructions for use in the patient information leaflet which is packed together with each inhaler.- That it is recommended to keep the device in the protective cover after opening the laminate pouch to enhance the stability of the product during use and makes the inhaler more tamper proof.- To shake and actuate the device prior to each inhalation.- In the sitting or standing position, to breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is delivered to the lungs.- Never to breathe out through the mouthpiece as this will result in a reduction in the delivered dose. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.- Never to actuate the device more than once without inhalation of the powder. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.- To always replace the dust cap and close the protective cover after use to prevent accidental actuation of the device (which could result in either overdosing or under dosing the patient when subsequently used). - To rinse the mouth out with water or brush the teeth after inhaling the prescribed dose to minimise the risk of oropharyngeal candidiasis and hoarseness.- To clean the mouthpiece with a dry cloth at regular intervals. Water should never be used for cleaning because the powder is sensitive to moisture. - To replace Easyhaler Budesonide when the counter reaches zero even though powder can still be observed within the device.
Paediatric populationIt is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.
PregnancyMost results from prospective epidemiological studies and world-wide post-marketing data have not been able to detect an increased risk for adverse effects for the foetus and newborn child from the use of inhaled budesonide during pregnancy. It is important for both foetus and mother to maintain an adequate asthma treatment during pregnancy. As with other drugs administered during pregnancy, the benefit of the administration of budesonide for the mother should be weighed against the risks to the foetus. The lowest effective dose of budesonide needed to maintain adequate asthma control should be used.In animal studies glucocorticosteroids have been shown to induce malformations (see section 5.3). 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.
BreastfeedingBudesonide is excreted in breast milk. However, at therapeutic doses of budesonide no effects on the suckling child are anticipated. Budesonide can be used during breast feeding.Maintenance treatment with inhaled budesonide (200 or 400 microg twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants.In a pharmacokinetic study, the estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th of the concentrations observed in maternal plasma, assuming complete infant oral bioavailability. Budesonide concentrations in infant plasma samples were all less than the limit of quantification.Based on data from inhaled budesonide and the fact that budesonide exhibits linear PK properties within the therapeutic dosage intervals after nasal, inhaled, oral and rectal administrations, at therapeutic doses of budesonide, exposure to the suckling child is anticipated to be low.Administration of inhaled budesonide 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.
|Common||Uncommon||Rare||Very rare||Not known|
|Infections and infestations||oropharyngeal candidiasis|
|Immune system disorders||hypersensitivity reactions (including rash contact dermatitis, urticaria, angioedema and anaphylactic reaction)|
|Endocrine disorders||hypocorticism, hypercorticism, signs and symptoms of systemic corticosteroid effects, including adrenal suppression and growth retardation*|
|Psychiatric disorders||anxiety**, depression**||behavioural changes (predominantly in children), restlessness, nervousness||psychomotor hyperactivity, sleep disorders, aggression, irritability, psychosis|
|Respiratory, thoracic and mediastinal disorders||cough, throat irritation||hoarseness, dysphonia, bronchospasm (see section 4.4)|
|Gastrointestinal disorders||difficulty in swallowing|
|Skin and subcutaneous tissue disorders||pruritus, erythema, bruising|
|Musculoskeletal and connective tissue disorders||muscle spasm||decreased bone density|
|Nervous system disorders||tremor|
*Paediatric populationDue to the risk of growth retardation in the paediatric population, growth should be monitored as described in section 4.4.**Clinical trials with 13119 patients on inhaled budesonide and 7278 patients on placebo have been pooled. The frequency of anxiety was 0.52% on inhaled budesonide and 0.63% on placebo; that of depression was 0.67% on inhaled budesonide and 1.15% on placebo.***In placebo-controlled studies, cataract was also uncommonly reported in the placebo group.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, www.mhra.gov.uk/yellowcard.
Topical anti-inflammatory effectThe exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions, such as inhibition of inflammatory mediator release and inhibition of cytokine-mediated immune response are probably important.
Onset of effectAfter a single dose of orally inhaled budesonide, delivered via dry powder inhaler, improvement of the lung function is achieved within a few hours. After therapeutic use of orally inhaled budesonide delivered via dry powder inhaler, improvement in lung function has been shown to occur within 2 days of initiation of treatment, although maximum benefit may not be achieved for up to 4 weeks.
Airway reactivityBudesonide has also been shown to decrease airway reactivity to histamine and methacholine in hyper-reactive patients.
Exercise-induced asthmaTherapy with inhaled budesonide has effectively been used for prevention of exercise-induced asthma.
HPA axis functionA study in healthy volunteers with Easyhaler Budesonide has shown dose-related effects on plasma and urinary cortisol. At recommended doses, budesonide causes less effect on the adrenal function than prednisolone 10mg, as shown by ACTH tests.
Paediatric populationLimited data from long term studies suggest that most children and adolescents treated with inhaled budesonide 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 (see section 4.4). Slit lamp examinations were performed in 157 children (5-16 years old), treated with an average daily dose of 504 μg for 3-6 years. Findings were compared with 111 age-matched asthmatic children. Inhaled budesonide was not associated with an increased occurrence of posterior subcapsular cataract.
Absorption:After oral administration of budesonide, peak plasma concentration is achieved in about 1-2 hours and the absolute systemic availability is 6-13%. In plasma, 85-95% of budesonide is bound to proteins. In contrast, peak plasma concentration is reached approximately 30 minutes after inhalation. Most of budesonide delivered to the lungs is systemically absorbed.
Distribution:Budesonide has a volume of distribution of approximately 3 L/kg. Plasma protein binding averages 85-90%.
Biotransformation and Elimination:Budesonide is mainly eliminated by metabolism. Budesonide is rapidly and extensively metabolised in liver via cytochrome P4503A4 to two major metabolites. The in vitro glucocorticoid activity of these metabolites is less than 1% of that of the parent compound. Negligible metabolic inactivation has been observed in human lung and serum preparations. Budesonide is excreted in urine and faeces in the form of conjugated and non-conjugated metabolites.
LinearityThe kinetics of budesonide are dose-proportional at clinically relevant doses.
Paediatric populationBudesonide has a systemic clearance of approximately 0.5 L/min in 4-6 years old asthmatic children. Per kg body weight children have a clearance which is approximately 50% greater than in adults. The terminal half-life of budesonide after inhalation is approximately 2.3 hours in asthmatic children. This is about the same as in healthy adults.
Special patient populationsThe exposure to budesonide may be increased in patients with liver disease.
As packaged for saleStore in the original package.For storage conditions after first opening of the medicinal product, see section 6.3.
Packages:Easyhaler Budesonide 200 micrograms/dose inhalation powder: 200 doses + protective cover 200 doses 2 x 200 dosesNot all pack sizes may be marketed.
Orion Pharma (UK) Limited
Oaklea Court, 22 Park Street, Newbury, Berkshire, RG14 1EA
+44 (0)1635 580 180
+44 (0)1635 520 300
+44 (0)1635 520 300