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Budelin® Novolizer® 200 micrograms per actuation inhalation powder


Active substance: Budesonide
One delivered dose contains 200 micrograms of budesonide.
10.7 mg of lactose monohydrate/delivered dose
The delivered dose is the dose which is available for the patient after passing
the mouthpiece.


Inhalation powder
White powder




Therapeutic indications
Regular treatment of persistent asthma.
Note: budesonide is not intended to be used as a reliever of acute asthma.


Posology and method of administration

Inhalation use
If a patient is switched to Budelin Novolizer 200 micrograms from an alternative
inhalation device the dose should be reviewed and adjusted, as necessary, on an
individual basis. The active substance, dose regimen and method of delivery should
be considered.
Steroid naive patients and patients previously controlled on inhaled steroids:
Adults (including older people) and children/adolescents over 12 years of age:

Initial recommended dose:
Maximum recommended dose:

200- 400 micrograms once or twice daily
800 micrograms twice daily

Children 6 - 12 years:
Initial recommended dose:
Maximum recommended dose:

200 micrograms twice or 200 – 400 micrograms
400 micrograms twice daily

Children below 6 years of age:
Budelin Novolizer 200 micrograms is not recommended for use in children below
age 6 due to insufficient data on safety and efficacy.
Note: For the 400 micrograms doses a 400 micrograms strength is available.
The dose should be adapted to the requirements of each individual, the severity of
the disease and the clinical response of the patient. The dose should be adjusted
until control is achieved and then should be titrated to the lowest dose at which
effective control of asthma is maintained.
Posology limits:
Adults (including older people) and children/adolescents over 12 years of age: 200 1600 micrograms daily
Children 6 - 12 years: 200 - 800 micrograms daily
Twice daily dosing in children and adults, including older people should be used
when starting treatment, during periods of severe asthma and while reducing or
discontinuing oral glucocorticosteroids.
Once daily dosing up to 800 micrograms may be used in adults, including older
people and children/adolescents over 12 years of age with mild to moderate asthma
already controlled on inhaled glucocorticosteroids (either budesonide or
beclometasone dipropionate) administered twice daily.
Once daily dosing up to 400 micrograms may be used in children 6-12 years of age
with mild to moderate asthma already controlled on inhaled glucocorticosteroids
(either budesonide or beclometasone dipropionate) administered twice daily.
If a patient is transferred from twice daily dosing to once daily dosing this should be
at the same equivalent total daily dose (with consideration of the active substance
and the method of delivery) and this dose should then be reduced to the minimum
dose needed to maintain effective control of asthma. The once daily regimen can be
considered only when asthma symptoms are controlled.
In case of once daily dosing this dose should be taken in the evening.
In case of deterioration of asthma control (recognised by e.g. persistent respiratory
symptoms, increased use of an inhaled bronchodilator) the dose of inhaled steroids

should be increased. Those patients receiving the once daily dose regimen, should
be advised to double their dose of inhaled corticosteroid, such that a once daily dose
would be administered twice daily. In any case of deterioration of asthma control
the patient should seek advice from a medical doctor as soon as possible.
A short acting inhaled beta-2-agonist should be available for the relief of acute
symptoms of asthma at all times.
Budelin Novolizer 200 micrograms may permit replacement or significant reduction
in dosage of oral glucocorticosteroids while maintaining asthma control. When
transferral from oral steroids to Budelin Novolizer 200 micrograms is started, the
patient should be in a relatively stable phase. A high dose of Budelin Novolizer 200
micrograms is then given in combination with the previously used oral steroid dose
for about 10 days.
After that, the oral steroid dose should be gradually reduced (by for example 2.5
milligrams prednisolone or the equivalent each month) to the lowest possible level.
In many cases, it is possible to completely substitute the oral steroid with Budelin
Novolizer 200 micrograms. For further information on the withdrawal of
corticosteroids, see section 4.4.
Mode and duration of treatment:
Budelin Novolizer 200 micrograms is intended for long-term therapy. It should be
administered regularly according to the recommended schedule even when the
patient is asymptomatic.
The improvement in the control of asthma can appear in 24 hours, although 1 - 2
weeks additional treatment period may be necessary to reach a maximum benefit.
In order to ensure that the active substance optimally reaches the intended site of
action it is necessary to inhale steadily, deeply and as rapidly as possible (to the
maximum inhalation). A clearly audible click and a colour change in the control
window from green to red indicates that inhalation has been performed correctly. If
an audible click is not heard and there is no colour change in the control window,
inhalation should be repeated. The inhaler remains locked until inhalation is
performed correctly.
To reduce the risk of oral candidiasis and hoarseness it is recommended that
inhalation be performed before meals and that the mouth is rinsed with water or the
teeth brushed after each inhalation.
Usage and handling of the powder inhaler (=Novolizer)

1. Lightly press together the ribbed surfaces on both sides of the lid, move the lid
forwards and lift off.
2. Remove the protective aluminium foil from the cartridge container and take out
the new cartridge.
3. Insert the cartridge into the powder inhaler (=Novolizer) with the dosage counter
facing the mouthpiece.
4. Replace the lid into the side guides from above and push down flat towards the
button until it snaps into place. The cartridge can be left in the powder inhaler
(=Novolizer) until it has been used up, or for up to 6 months after insertion.
Note: Budelin Novolizer 200 micrograms cartridges may only be used in the
Novolizer powder inhaler
1. When using the powder inhaler (=Novolizer) always keep it horizontal. First
remove the protective cap.
2. Completely depress the coloured button. A loud double click will be heard and
the colour of the control window (lower) will change from red to green. Then
release the coloured button. The colour green in the window indicates that the
powder inhaler (=Novolizer)is ready for use.
3. Exhale as far as possible (but not into the powder inhaler).
4. Put the lips around the mouthpiece. Inhale the powder with a deep breath. During
this breath a loud click should be heard, indicating correct inhalation. Hold the
breath for a few seconds and then continue with normal breathing.

Note: If the patient needs to take more than 1 actuation at a time, steps 2 - 4 should
be repeated.
5. Replace the protective cap on the mouth piece - the dosing procedure is now
6. The number in the top window indicates the number of inhalations left.
Note: The coloured button should only be pressed immediately before inhalation.
A double inhalation in error is not possible with the powder inhaler (=Novolizer).
The click sound and the change of colour in the control window indicate that
inhalation has been performed correctly. If the colour of the control window does
not change then inhalation should be repeated. If inhalation is not completed
correctly after several attempts, then the patient should consult the doctor/physician.
The powder inhaler (=Novolizer) should be cleaned at regular intervals, but at least
every time the cartridge is changed. Instructions on how to clean the powder inhaler
(=Novolizer) can be found in the operating instructions attached.
Note: In order to ensure correct use of the inhaler, patients should receive thorough
instructions on how to use the powder inhaler (=Novolizer). Children should only
use this product under the supervision of an adult.

Hypersensitivity to the active substance budesonide or to the excipient lactose
monohydrate (which contains small amounts of milk proteins).

Special warnings and precautions for use
Budesonide is not indicated for treatment of acute dyspnoea or status asthmaticus.
These conditions should be treated in the normal way.
Treatment of acute exacerbations of asthma and asthma symptoms may need an
increase in the dose of budesonide. The patient should be advised to use a shortacting inhaled bronchodilator as rescue medication to relieve acute asthma
Close observation and special care is needed in patients with both active and
quiescent pulmonary tuberculosis. Patients with active pulmonary tuberculosis may
use budesonide only if they are treated simultaneously with effective
tuberculostatics. Similarly patients with fungal, viral or other infections of the
airways require close observation and special care and should use budesonide only
if they are also receiving adequate treatment for such infections.
Patients who repeatedly fail to perform the inhalation correctly should consult their

In patients with severe hepatic dysfunction treatment with budesonide - similar to
treatment with other glucocorticosteroids - may lead to a reduced elimination rate
and an increase in systemic availability. Attention is to be paid to possible systemic
effects. Therefore the hypothalamic pituitary adrenocortical (HPA) axis function of
these patients should be checked at regular intervals.
Prolonged treatment with high doses of inhaled corticosteroids, particularly higher
than the recommended doses, may result in clinically significant adrenal
suppression. These patients may exhibit signs and symptoms of adrenal
insufficiency when exposed to severe stress. Additional systemic corticosteroid
cover should be considered during periods of stress or elective surgery.
Systemic effects may occur with any inhaled corticosteroids, particularly at high
doses prescribed for prolonged 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,
glaucoma and more rarely, a range of psychological or behavioural effects including
psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression
(particularly in children). It is important therefore that the dose of inhaled
corticosteroid is titrated to the lowest dose at which effective control of asthma is
Concomitant use of ketoconazole, HIV protease inhibitors or other potent CYP3A4
inhibitors should be avoided. If this is not possible, the period between treatments
should be as long as possible (see also section 4.5).
Oral candidiasis may occur during the therapy with inhaled corticosteroids. This
infection may require treatment with appropriate antifungal therapy and in some
patients discontinuation of treatment may be necessary (see also section 4.2).
As with other inhalation therapy paradoxical bronchospasm may occur with an
immediate increase in wheezing after dosing. If this occurs, treatment with inhaled
budesonide should be discontinued immediately, the patient assessed and alternative
therapy instituted if necessary.
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. 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.
Precautions for patients not previously treated with corticosteroids:
When budesonide is used regularly as directed, patients who have previously never
or only occasionally received brief treatment with corticosteroids, should experience
an improvement in breathing after approximately 1 - 2 weeks. However, extreme
mucous congestion and inflammatory processes may obstruct the bronchial passages
to such an extent that budesonide cannot fully exert its local effects. In such cases,

inhaled therapy with budesonide should be supplemented with a short course of
systemic corticosteroids. Inhalation doses are continued after gradually reducing the
dose of systemic corticosteroids.
Precautions for switching patients from systemically active corticosteroids to
inhalation treatment:
Patients receiving systemic treatment with corticosteroids should be switched to
Budelin Novolizer 200 micrograms at a time when their symptoms are under
control. In these patients, whose adrenocortical function is usually impaired,
systemic treatment with corticosteroids must not be stopped abruptly. At the
beginning of the switchover, a high dose of Budelin Novolizer 200 micrograms
should be given in addition to the systemic corticosteroids for about 7 to 10 days.
Then, depending on the patient's response and depending on the original dose of the
systemic steroid, the daily dose of the systemic corticosteroid can be reduced
gradually (e.g. 1 milligram prednisolone or the equivalent each week or 2.5
milligram prednisolone or the equivalent each month).The oral steroid should be
reduced to the lowest possible level and it may be possible to completely replace the
oral steroid with inhaled budesonide.
Within the first few months of switching patients from systemic administration of
corticosteroids to inhalation treatment, it may be necessary to resume systemic
administration of corticosteroids during periods of stress or in the case of
emergencies (e.g. severe infections, injuries, surgery). This applies also to patients
who have received prolonged treatment with high doses of inhaled corticosteroids.
They may also have impaired adrenocortical function and may need systemic
corticosteroid cover during periods of stress.
Recovery from impaired adrenal function may take some considerable time.
Hypothalamic pituitary adrenocortical axis function should be monitored regularly.
The patient might feel generally unwell in a non specific way during the withdrawal
of systemic corticosteroids despite maintenance or even improvement in respiratory
function. The patient should be encouraged to continue with inhaled budesonide and
withdrawal of oral steroids unless there are clinical signs which might indicate
adrenal insufficiency.
After the patient has been switched to inhalation treatment, symptoms may become
manifest that had been suppressed by the previous systemic treatment with
glucocorticosteroids, e.g. allergic rhinitis, allergic eczema, muscle and joint pain.
Suitable medicinal products should be co-administered to treat these symptoms.
Inhaled budesonide should not be stopped abruptly.
Exacerbation of clinical symptoms due to acute respiratory tract infections:
If clinical symptoms become exacerbated by acute respiratory tract infections,
treatment with appropriate antibiotics should be considered. The dose of budesonide
can be adjusted as required and, in certain situations, systemic treatment with
glucocorticosteroids may be indicated.

If no improvement of symptoms or adequate asthma control is seen within 14 days
of treatment, medical advice is sought for either adjusting the dose or clarifying
correct inhalation procedure.
Precautions for switching patients from Budelin Novolizer 200 micrograms to
Budelin Novolizer 400 micrograms:
Patients who are not able to produce flow rates above 60 l/min and children need
careful monitoring when they begin treatment with the same dose but are switched
from Budelin Novolizer 200 micrograms to Budelin Novolizer 400 micrograms.
Lactose may contain milk protein. The amount of lactose contained in Budelin
Novolizer 200 micrograms does not normally cause problems in lactose intolerant
people. However, in patients with profound enzyme deficiency, lactose intolerance
has been reported very rarely following inhalation of powder containing lactose.


Interaction with other medicinal products and other forms of interaction
The metabolism of budesonide is primarily mediated by CYP3A4. Inhibitors
of this enzyme, eg, ketoconazole, itraconazole, HIV protease inhibitors can
therefore increase systemic exposure to budesonide several times, see section
4.4. Since there is no data to support a dosage recommendation, the
combination should be avoided. If this is not possible, the period between
treatments should be as long as possible and a reduction of the budesonide
dose could also be considered.
Limited data about this interaction for high-dose inhaled budesonide indicate
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 1000 μg).
Raised plasma concentrations of and enhanced effects of corticosteroids have
been observed in women also treated with oestrogens and contraceptive
steroids, but no effect has been observed with budesonide and concomitant
intake of low dose combination oral contraceptives.
Because adrenal function may be suppressed, an ACTH stimulation test for
diagnosing pituitary insufficiency might show false results (low values).


Fertility, pregnancy and lactation

Results from a large prospective epidemiological study and from world-wide post
marketing experience indicate that inhaled budesonide during pregnancy has no
adverse effects on the health of the foetus / new born child.
As with other drugs the administration of budesonide during pregnancy requires that
the benefits for the mother are weighed against the risks for the foetus.

Budesonide is excreted in breast milk. However, at therapeutic doses no effects on
the suckling child are anticipated. Budelin Novolizer 200 micrograms 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.
Effects on ability to drive and use machines
Budesonide has no influence on the ability to drive and use machines.

Undesirable effects

Adverse events are listed below 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); Very rare (< 1/10,000); Not known (cannot
be estimated from the available data)
Table on Adverse Drug Reaction (ADR) by System Organ Class (SOC) and


Adverse Drug Reaction



Oropharyngeal candidiasis






Immediate and delayed
hypersensitivity reactions including:
Angioneurotic oedema
Anaphylactic reaction
Signs and symptoms of systemic
corticosteroid effects including:
Adrenal suppression and
Growth retardation*
Behavioural changes (predominantly







Very rare

in children)
Sleep disorders
Psychomotor hyperactivity
Throat irritation
Oral mucosal irritation
Bone density decreased

* refer to Paediatric population, below
** rare in children

Mild mucosal irritations accompanied by throat irritation, hoarseness and cough
may commonly occur.

The susceptibility to infection can be increased. The ability to adapt to stress can be
There is an increased risk of pneumonia in patients with newly diagnosed COPD
starting treatment with inhaled corticosteroids. However a weighted assessment of 8
pooled clinical trials involving 4643 COPD patients treated with budesonide and
3643 patients randomized to non-ICS treatments did not demonstrate an increased
risk for pneumonia. The results from the first 7 of these 8 trials have been published
as a metaanalysis.
Lactose-monohydrate contains small amounts of milk proteins and can therefore
cause allergic reactions.
Paediatric population
Due to the risk of growth retardation in the paediatric population, growth should be
monitored as described in section 4.4.
Reporting of suspected adverse reactions

Reporting 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 at

Acute overdose with Budelin Novolizer 200 micrograms, even in excessive
doses, is not expected to be a clinical problem.




Pharmacodynamic properties

DISEASES, INHALANTS; Glucocorticoids ATC-Code: R03BA02
Budesonide is a synthetic glucocorticoid. After oral inhalation, it has a local antiinflammatory effect on the bronchial mucosa.
Budesonide penetrates cellular membranes and binds to a cytoplasmic receptor
protein. This complex enters the nucleus and induces there the biosynthesis of
specific proteins, like macrocortin (lipocortin). The hormone-like effects occur after
a certain latency period (30-60 min) and result in an inhibition of phospholipase A2.
It is also possible that therapeutically effective doses of Budesonide (like other antiinflammatory glucocorticosteroids) suppress cytokine-induced COX-2 expression.
Clinically, the anti-inflammatory effect results e.g. in improvement of the
symptoms, such as dyspnoea. The hyperresponsiveness of the bronchial tract to
exogenic challenges is reduced.
Clinical Safety
Paediatric population
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.
Influence on plasma cortisol concentration
Studies in healthy volunteers with inhaled budesonide have shown dose-related
effect on plasma and urinary cortisol. At recommended doses, inhaled budesonide
causes significantly less effect on adrenal function than prednisone 10 mg, as shown
by ACTH test.

Pharmacokinetic properties


Peak plasma levels appear approximately 30 minutes after inhalation.
Systemic bioavailability after inhalation is up to 37% and the concentration in
human plasma after inhalation of a single dose of 1600 micrograms is 0.63 nmol/L.
The trigger threshold of the powder inhaler (=Novolizer)which must be overcome
for successful inhalation is to be found at inspiratory flows through the inhaler of 35
- 50 l/min. Dose linearity for switching from Budesonide Novolizer 200 µg to
Budesonide Novolizer 400 µg was shown at flow rates of 60 l/min upwards.
The fine particle dose (particles < 5 µm) measured in vitro in the clinically relevant
range is approximately 30 – 50 % related to the nominal dose. In healthy subjects,
approximately 20 – 30 % of the metered dose of budesonide pass into the lungs. The
remainder deposits in mouth, nose and throat and a large part of it is swallowed.
Budesonide has a volume of distribution of approximately 3 L/kg. Plasma protein
binding averages 85-90%.
Budesonide undergoes an extensive degree (≈90%) of biotransformation on first
passage through the liver to metabolites of low glucocorticosteroid activity. The
glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide
and16α-hydroxyprednisolone, is less than 1% of that of budesonide. The
metabolism of budesonide is primarily mediated by CYP3A, a subfamily of
cytochrome p450.
The metabolites of budesonide are excreted as such or in conjugated form mainly
via the kidneys. No unchanged budesonide has been detected in the urine.
Budesonide has high systemic clearance (approximately 1.2 L/min) in healthy
adults, and the terminal half-life of budesonide after iv dosing averages 2-3 hours.
The kinetics of budesonide are dose-proportional at clinically relevant doses.
Paediatric population
Budesonide 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.

Preclinical safety data
Preclinical data revealed no special hazard for humans at therapeutic doses
based on studies of chronic toxicity, genotoxicity and carcinogenicity.
Glucocorticosteroids, including budesonide, have produced teratogenic effects
in animals, including cleft palate and skeletal abnormalities. Similar effects are
considered unlikely to occur in humans at therapeutic doses.




List of excipients
Lactose monohydrate


Not applicable


Shelf life
• Medicinal product (Budesonide in the cartridge packed in a container)
Shelf life before opening the container
3 years
Shelf life after first opening the container
6 months
• Device (Powder inhaler =Novolizer)
Shelf life before first use
3 years
In-use shelf life
1 year
To note: The functioning of the powder inhaler (=Novolizer) has been
demonstrated in tests for 2000 metered doses. Therefore a maximum of 10
cartridges containing 200 metered doses or 20 cartridges containing 100
metered doses can be used with this device (within a single year) prior to


Special precautions for storage
Store in the original package. This medicinal product does not require any
special temperature storage conditions.
In-Use storage conditions: Keep the Novolizer device tightly closed, in order
to protect from moisture.


Nature and contents of container

1 Polystyrene/polypropylene cartridge containing 100 or 200 metered doses,
equivalent to the filling amount of 1.09 g or 2.18 g of powder packed in a
polypropylene container sealed by aluminium foil.1 Novolizer powder inhaler
device (mouthpiece in polycarbonate and powder inhaler in
acrylnitrilbutadienestyrol copolymer, polyoxymethylene).
Pack sizes:
Original sales packs:
1 cartridge containing 100/200 metered doses and 1 Novolizer powder inhaler
2 cartridges containing 200 metered doses each and 1 Novolizer powder
inhaler device
Refill packs:
1 cartridge containing 100 metered doses (UK and Ireland only)
1 cartridge containing 200 metered doses
2 cartridges containing 200 metered doses each
Hospital pack:
(1 cartridge containing 100 metered doses and 1 Novolizer powder inhaler
device) x 10
Sample pack:
1 cartridge containing 100 metered doses and 1 Novolizer powder inhaler
1 cartridge containing 200 metered doses and 1 Novolizer powder inhaler
Not all pack sizes may be marketed

Special precautions for disposal
No special requirements.


Meda Pharmaceuticals Ltd
Skyway House
Parsonage Road
Bishops Stortford
CM22 6PU


PL 15142/0054





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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.