Սինգապուր - անգլերեն - HSA (Health Sciences Authority)
Dry powder for inhalation
budesonide/formoterol fumarate dihydrate
320 mcg/9 mcg
Dry powder for inhalation
budesonide/formoterol fumarate dihydrate
Read all of this leaﬂet carefully before you start using this
medicine because it contains important information for you.
Keep this leaﬂet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or
This medicine has been prescribed for you only. Do not pass it on
to others. It may harm them, even if their signs of illness are the
same as yours.
If you get any side effects, talk to your doctor, pharmacist or
nurse. This includes any possible side effects not listed in this
leaﬂet. See section 4.
What is in this leaﬂet
1. What DuoResp Spiromax is and what it is used for
2. What you need to know before you use DuoResp
3. How to use DuoResp Spiromax
4. Possible side effects
5.How to store DuoResp Spiromax
6.Contents of the pack and other information
What DuoResp Spiromax is and what
it is used for
DuoResp Spiromax contains two different active substances:
budesonide and formoterol fumarate dihydrate.
Budesonide belongs to a group of medicines called ‘corticosteroids’
also known as ‘steroids’. It works by reducing and preventing
swelling and inﬂammation in your lungs and helps you to breathe
Formoterol fumarate dihydrate belongs to a group of medicines
called ‘long-acting β
adrenoceptor agonists’ or ‘bronchodilators’.
It works by relaxing the muscles in your airways. This will help to
open the airways and help you to breathe more easily.
Your doctor has prescribed this medicine to treat asthma or chronic
obstructive pulmonary disease (COPD).
When used for asthma, your doctor will prescribe DuoResp Spiromax
together with a separate ‘reliever inhaler’ such as salbutamol.
Use DuoResp Spiromax every day. This helps to prevent asthma
symptoms such as breathlessness and wheezing from occurring.
Use the ‘reliever inhaler’ when you get asthma symptoms, to make
it easier to breathe again.
Do not use DuoResp Spiromax 320/9 micrograms as a ‘reliever inhaler’.
Chronic obstructive pulmonary disease (COPD)
COPD is a long-term lung disease of the airways in the lungs, which is
often caused by cigarette smoking. Symptoms include shortness of
breath, cough, chest discomfort and coughing up mucus. DuoResp
Spiromax can also be used to treat the symptoms of COPD in
What you need to know before you
use DuoResp Spiromax
Do not use DuoResp Spiromax if
You are allergic to budesonide, formoterol fumarate dihydrate, or the
other ingredient in this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor,pharmacist or nurse before taking DuoResp
you are diabetic.
you have a lung infection.
you have high blood pressure or you have ever had a heart problem
(including an uneven heartbeat, a very fast pulse, narrowing of the
arteries or heart failure).
you have problems with your thyroid or adrenal glands.
you have low levels of potassium in your blood.
you have severe liver problems.
you regularly drink alcohol.
If you have been taking steroid tablets for your asthma or COPD, your
doctor may reduce the number of tablets that you take, once you start
to use DuoResp Spiromax. If you have been taking steroid tablets for
a long time, your doctor may want you to have regular blood tests.
When reducing steroid tablets, you may feel generally unwell even
though your chest symptoms may be improving. You might experience
symptoms such as a stuffy or runny nose, weakness or joint or muscle
pain and rash (eczema). If any of these symptoms bother you, or if
symptoms such as headache, tiredness, nausea (feeling sick) or
vomiting (being sick) occur, please contact your doctor immediately.
You may need to take other medicines if you develop allergic or
arthritic symptoms. You should speak to your doctor if you are
concerned as to whether you should continue to use DuoResp
Your doctor may consider adding steroid tablets to your usual
treatment if you have an illness such as a chest infection or before an
Contact your doctor if you experience blurred vision or other visual
This medicine should not be used in children under the age of
Other medicines and DuoResp Spiromax
Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines.
In particular, tell your doctor or pharmacist if you are taking any of the
β blockers (such as atenolol or propranolol for high blood pressure
or a heart condition), including eyedrops (such as timolol for
Oxytocin which is given to pregnant women to induce labour.
Medicines for a fast or uneven heartbeat (such as quinidine,
disopyramide, procinamide and terfanidine).
Medicines like digoxin, often used to treat heart failure.
Diuretics, also known as ‘water tablets’ (such as furosemide).
These are used to treat high blood pressure.
Steroid tablets that you take by mouth (such as prednisolone).
Xanthine medicines (such as theophylline or aminophylline).
These are often used to treat asthma.
Other bronchodilators (such as salbutamol).
Tricyclic antidepressants (such as amitriptyline) and the
Antidpressant medicines such as monoamine oxidase inhibitors and
those with similar properties (such as the antibiotic furazolidine
and the chemotherapy medicine procarbazine).
Antipsychotic phenothiazine medicines (such as chlorpromazine
Medicines called ‘HIV protease inhibitors’ (such as ritonavir) to treat
Medicines to treat infections (such as ketoconazole, itraconazole,
voriconazole, posaconazole, clarithromycin and telithromycin).
Medicines for Parkinson’s disease (such as levodopa).
Medicines for thyroid problems (such as levothyroxine).
Some medicines may increase the effects of DuoResp Spiromax and
your doctor may wish to monitor you carefully if you are taking these
medicines (including some medicines for HIV: ritonavir, cobicistat).
If any of the above applies to you, or if you are not sure, talk to your
doctor,pharmacist or nurse before using DuoResp Spiromax.
Also tell your doctor,pharmacist or nurse if you are going to have a
general anaesthetic for an operation or for dental work to help lower
any risk of interaction with the anesthetic you receive.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or
are planning to have a baby, ask your doctor, pharmacist or nurse
for advice before taking DuoResp Spiromax - do NOT use this
medicine unless your doctor tells you to.
If you get pregnant while using DuoResp Spiromax, do NOT stop
using DuoResp Spiromax but talk to your doctor immediately.
Driving and using machines
DuoResp Spiromax is not likely to affect your ability to drive or to use
tools or machines.
DuoResp Spiromax contains lactose
Lactose is a type of sugar found in milk. If you have been told by your
doctor that you have an intolerance to some sugars, talk to your
doctor before using this medicine.
How to use DuoResp Spiromax
Always use this medicine exactly as your doctor or pharmacist has
told you. Check with your doctor pharmacist, or nurse if you are
It is important to use DuoResp Spiromax every day, even if you
have no asthma or COPD symptoms at the time.
If you are using DuoResp Spiromax for asthma, your doctor will
want to regularly check your symptoms.
Use your DuoResp Spiromax every day. This helps to prevent
asthma symptoms from occurring.
Adults (18 years and older)
1 inhalation (actuation), twice a day, taken in the morning and in the
Your doctor may increase this to 2 inhalations, twice a day.
If your symptoms are well controlled, your doctor may ask you to take
your medicine once a day.
Adolescents (12 – 17 years)
1 inhalation twice daily.
Your doctor will help you to manage your asthma and will adjust the
dose of this medicine to the lowest dose that controls your asthma. If
your doctor feels that you need a lower dose than is available from
your DuoResp Spiromax, your doctor may prescribe an alternative
inhaler containing the same active substances as your DuoResp
Spiromax but with a lower dose of the corticosteroid. However, do not
adjust the number of inhalations your doctor has prescribed without
talking to your doctor ﬁrst.
Use your separate ‘reliever inhaler’ to treat asthma symptoms
when they happen.
Always keep your ‘reliever inhaler’ with you and use it to relieve
sudden attacks of breathlessness and wheezing. Do not use DuoResp
Spiromax to treat these asthma symptoms.
Chronic Obstructive Pulmonary Disease (COPD)
1 inhalation twice a day, taken in the morning and in the evening.
Preparing your new DuoResp Spiromax
Before using your DuoResp Spiromax for the ﬁrst time, you need to
prepare it for use as follows:
Open the foil pouch by tearing at the notch at the top of the foil
pouch and take out the inhaler
Check the dose indicator to see that there are 60 inhalations in the
Write the date you opened the foil pouch on the label of the
Do not shake your inhaler before use.
How to take an inhalation
Every time you need to take an inhalation, follow the instructions
Hold your inhaler with the semi-transparent wine red
mouthpiece cover at the bottom.
Open the mouthpiece cover by folding it down until one loud click
is heard. Your medicine is actively metered. Your inhaler is now
ready for use.
Breathe out gently (as far as is comfortable). Do not breathe out
through your inhaler.
Place the mouthpiece between your teeth. Do not bite the
mouthpiece. Close your lips around the mouthpiece. Take care not
to block the air vents.
Breathe in through your mouth as deeply and as hard as you can.
Remove your inhaler from your mouth. You may notice a taste
when you take your inhalation
Hold your breath for 10 seconds or as long as you comfortably
Then breathe out gently (do not breathe out through the
inhaler). Close the mouthpiece cover.
If you are to take a second inhalation, repeat steps 1 to 7.
Rinse your mouth with water after every dose and spit it out.
Do not try to take your inhaler apart, remove or twist the mouthpiece
cover, it is ﬁxed to your inhaler and must not be taken off. Do not use
your Spiromax if it has been damaged or if the mouthpiece has come
apart from your Spiromax. Do not open and close the mouthpiece
cover unless you are about to use your inhaler.
Cleaning your Spiromax
Keep your Spiromax dry and clean.
If necessary you may wipe the mouthpiece of your Spiromax after use
with a dry cloth or tissue.
When to start using a new Spiromax
The dose indicator tells you how many doses (inhalations) are left
in your inhaler, starting with 60 inhalations when it is full and
ending with 0 (zero) inhalations when it is empty.
The dose indicator, on the rear of the device, shows the number of
inhalations remaining as even numbers. The spaces between the
even numbers represent the odd number of remaining inhalations.
For inhalations remaining from 20 downwards to ‘8’, ‘6’, ‘4’, ‘2’ the
numbers are displayed in red on a white background. When the
numbers become red in the window, you should consult your doctor
and obtain a new inhaler.
The mouthpiece will still ‘click’ even when your Spiromax is empty.
If you open and close the mouthpiece without taking an inhalation,
the dose indicator will still register it as a count. This dose will be
securely held inside the inhaler for when the next inhalation is due. It
is impossible to accidentally take extra medicine or a double dose in
Keep the mouthpiece closed all the time unless you are about to
use your inhaler.
Important information about your asthma or COPD symptoms
If you feel you are getting breathless or wheezy while using DuoResp
Spiromax, you should continue to use DuoResp Spiromax but go to
see your doctor as soon as possible, as you may need additional
Contact your doctor immediately if:
Your breathing is getting worse or you often wake up at night with
breathlessness and wheezing.
Your chest starts to feel tight in the morning or your chest
tightness lasts longer than usual.
These signs could mean that your asthma or COPD is not being
properly controlled and you may need different or additional
Once your asthma is well controlled your doctor may consider it
appropriate to gradually reduce the dose of DuoResp Spiromax.
If you use more DuoResp Spiromax than you should
It is important that you take your dose as advised by your doctor. You
should not exceed your prescribed dose without seeking medical
If you use more DuoResp Spiromax than you should, contact your
doctor, pharmacist or nurse for advice.
The most common symptoms that may occur after when you use more
DuoResp Spiromax than you should are trembling, headache or a rapid
If you forget to use DuoResp Spiromax
If you forget to take a dose, take it as soon as you remember.
However, do not take a double dose to make up for a forgotten dose.
If it is nearly time for your next dose just take your next dose at the
If you become wheezy or breathless, or develop any other symptoms
of an asthma attack, use your ‘reliever inhaler’, then seek medical
If you stop using DuoResp Spiromax
Do not stop using your inhaler without telling your doctor ﬁrst.
If you have any further questions on the use of this medicine, ask
your doctor, pharmacist or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not
everybody gets them.
If any of the following happen to you, stop using DuoResp
Spiromax and talk to your doctor immediately:
Rare side effects: may affect up to 1 in 1,000 people
Swelling of your face, particularly around your mouth (tongue and/
or throat and/or difficulty to swallow) or hives together with
difficulties to breathe (angioedema) and/or sudden feeling of
faintness. This may mean that you are having an allergic reaction,
which may also include rash and itching.
Bronchospasm (tightening of the muscles in the airways which causes
wheezing and shortness of breath). If the wheezing comes on
suddenly after using this medicine stop using it and talk to your doctor
immediately (see below).
Very rare side effects: may affect up to 1 in 10,000 people
Sudden, unexpected and acute wheezing and/or shortness of
breath immediately after using your inhaler (also referred to as
‘paradoxical bronchospasm’. If either of these symptoms occur,
stop using DuoResp Spiromax straightaway and use your
’reliever inhaler’ if you have one. Contact your doctor immediately
as you may need to have your treatment changed.
Other possible side effects:
Common: may affect up to 1 in 10 people
Palpitations (awareness of your heart beating), trembling or
shaking. If these effects occur, they are usually mild and usually
disappear as you continue to use DuoResp Spiromax.
Thrush (a fungal infection) in the mouth. This is less likely to occur
if you rinse your mouth out with water after using your medicine.
Mild sore throat, coughing and a hoarse voice.
Pneumonia (infection to the lung) in COPD patients.
Tell your doctor if you have any of the following while taking DuoResp
Spiromax they could be symptoms of a lung infection:
Fever or chills
Increased mucus production, change in mucus colour
Increased cough or increased breathing difficulties
Uncommon: may affect up to 1 in 100 people
Feeling restless, nervous, agitated, anxious or angry.
Nausea (feeling sick).
Bruising of the skin.
Low levels of potassium in your blood.
Changes in behaviour, especially in children.
Chest pain or tightness in the chest (angina pectoris).
Disturbance of the heart’s electrical system which does not cause
symptoms (prolongation of the QTc-interval).
An increase in the amount of sugar (glucose) in your blood, when
you have a blood test.
Taste changes, such as an unpleasant taste in the mouth.
Changes in your blood pressure.
Inhaled corticosteroids can affect the normal production of steroid
hormones in your body, particularly if you use high doses for a long
time. The effects include:
changes in bone mineral density (thinning of the bones)
cataract (clouding of the lens in the eye)
glaucoma (increased pressure in the eye)
a slowing of the rate of growth of children and adolescents
an effect on the adrenal gland (a small gland next to the kidney).
Symptoms of adrenal gland suppression could be tiredness,
weakness, stomach problems, including nausea, vomiting, pain and
diarrhoea, darkening of the skin and weight loss.
These effects happen very rarely and are much less likely to happen
with inhaled corticosteroids than with corticosteroid tablets.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse.
This includes any possible side effects not listed in this leaﬂet.
How to store DuoResp Spiromax
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on
the carton or on the label of your inhaler after EXP. The expiry date
refers to the last day of that month.
Do not store above 30
C. Keep the mouthpiece cover closed
after removal of the foil wrapping.
Use within 3 months of removing from the foil wrapping.
Use the label on the inhaler to write down the date you open the
Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines you no
longer use. These measures will help protect the environment.
Contents of the pack and other
What DuoResp Spiromax contains
— The active substances are budesonide and formoterol fumarate
dihydrate. Each delivered (inhaled) dose contains
320 micrograms of budesonide and 9 micrograms of formoterol
fumarate dihydrate. This is equivalent to a metered dose of
400 micrograms of budesonide and 12 micrograms of formoterol
— The other ingredient is lactose monohydrate (see section 2
under ‘DuoResp Spiromax contains lactose’).
What DuoResp Spiromax looks like and contents of the pack
DuoResp Spiromax is an inhalation powder.
Each DuoResp Spiromax inhaler contains 60 inhalations and has a
white body with a semi-transparent wine red mouthpiece cover.
Packs of 1, 2, and 3 inhalers. Not all pack sizes may be marketed in
Norton (Waterford) Limited T/A Teva
Unit 27/35, IDA Industrial Park, Cork Road,
This leaﬂet was last revised in September 2020.
Package leaflet: Information for the patient
320 mcg/9 mcg
NAME OF THE MEDICINAL PRODUCT
Dry powder for inhalation 320 mcg/9 mcg
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each delivered dose (the dose that leaves the mouthpiece of the Spiromax)
contains 320 micrograms of budesonide and 9 micrograms of formoterol
This is equivalent to a metered dose of 400 micrograms budesonide and
12 micrograms of formoterol fumarate dihydrate.
Excipient(s) with known effect:
Each dose contains approximately 10 milligrams of lactose (as monohydrate).
For the full list of excipients, see section 6.1.
White inhaler with a semi-transparent wine red mouthpiece cover.
DuoResp Spiromax is indicated in the regular treatment of asthma, where
use of a combination (inhaled corticosteroid and long-acting β
agonist) is appropriate:
− in patients not adequately controlled with inhaled corticosteroids and “as
needed” inhaled short-acting β
− in patients already adequately controlled on both inhaled corticosteroids
and long-acting β
Chronic Obstructive Pulmonary Disease (COPD)
Symptomatic treatment of patients with COPD with FEV1 <70% predicted
normal (post-bronchodilator) and a history of repeated exacerbations,
despite regular long-acting bronchodilator therapy (see section Special
warnings and precautions for use).
Posology and method of administration
DuoResp Spiromax is not intended for the initial management of asthma.
The dosage of the components of DuoResp Spiromax 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 β
-agonists and/or corticosteroids by individual inhalers
should be prescribed.
Adults (18 years and older): 1 inhalation twice daily. Some patients may
require up to a maximum of 2 inhalations twice daily.
Adolescents (12-17 years): 1 inhalation twice daily.
Patients should be regularly reassessed by their prescriber/healthcare
provider, so that the dosage of DuoResp Spiromax remains optimal. The dose
should be titrated to the lowest dose at which effective control of symptoms
is maintained. When control of symptoms is maintained with the lowest
recommended dosage, then the next step could include a test of inhaled
In usual practice when control of symptoms is achieved with the twice-daily
regimen, titration to the lowest effective dose could include DuoResp
Spiromax given once daily, when in the opinion of the prescriber, a
long-acting bronchodilator would be required to maintain control.
DuoResp Spiromax 320 micrograms/9 micrograms should be used as
maintenance therapy only. A lower strength of DuoResp Spiromax is
available for the maintenance and reliever therapy regimen.
Adults: 1 inhalation twice daily
Special patient groups: There are no special dosing requirements for
elderly patients. There are no data available for use of DuoResp Spiromax 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
Spiromax is a breath actuated, inspiratory ﬂow-driven inhaler, which means
that the active substances are delivered into the airways when the patient
inhales through the mouthpiece.
Moderate and severe asthmatic patients were shown to be able to generate
sufficient inspiratory ﬂow rate for Spiromax to deliver the therapeutic dose
(see section 5.1).
DuoResp Spiromax should be used correctly in order to achieve effective
treatment. As such, the patients should be advised to read the patient
information leaﬂet carefully and follow the instructions for use as detailed in
The use of DuoResp Spiromax follows three simple steps: open, breathe and
close which are outlined below.
Open: Hold the Spiromax with the mouthpiece cover at the bottom and open
the mouthpiece cover by folding it down until it is fully opened when one
click is heard.
Breathe: Place the mouthpiece between the teeth with the lips closed
around the mouthpiece, do not bite the mouthpiece of the inhaler. Breathe in
forcefully and deeply through the mouthpiece. Remove the Spiromax from
mouth and hold the breath for 10 seconds or as long as comfortable for the
Close: Breathe out gently and close the mouthpiece cover
It is also important to advise patients not to shake the inhaler before use and
not to breathe out through the Spiromax and not to block the air vents when
they are preparing the “Breathe” step.
Patients should also be advised to rinse their mouth with water after
inhaling (see section 4.4)
The patient may notice a taste when using DuoResp Spiromax due to the
Hypersensitivity to the active substances or the excipient listed in section 6.1.
Special warnings and precautions for use
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 DuoResp Spiromax, medical attention must be sought
(see section 4.2). Sudden and progressive deterioration in control of asthma
or COPD 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 DuoResp Spiromax (for asthma patients using DuoResp Spiromax as
maintenance and reliever therapy) or a separate rapid-acting bronchodilator
(for asthma patients using DuoResp Spiromax as maintenance therapy only).
Patients should be reminded to take their DuoResp Spiromax maintenance
dose as prescribed, even when asymptomatic. The prophylactic use of
DuoResp Spiromax, e.g. before exercise, has not been studied. The reliever
inhalations of DuoResp Spiromax should be taken in response to symptoms
but are not intended for regular prophylactic use, e.g. before exercise. For
such, a separate rapid-acting bronchodilator should be considered.
Patients should be reassessed regularly by their prescriber/healthcare
provider so that the dose of DuoResp Spiromax remains optimal. The dose
should be titrated to the lowest dose at which effective control of symptoms
is maintained. Once asthma symptoms are controlled, consideration may be
given to gradually reducing the dose of DuoResp Spiromax. When it is
appropriate to titrate down to a lower strength than is available for DuoResp
Spiromax, a change to an alternative ﬁxed-dose combination of budesonide
and formoterol fumarate containing a lower dose of the inhaled
corticosteroid is required.
Regular review of patients as treatment is stepped down is important.
Patients should not be initiated on DuoResp Spiromax during an
exacerbation, or if they have signiﬁcantly worsening or acutely deteriorating
Serious asthma-related adverse reactions and exacerbations may occur
during treatment with DuoResp Spiromax. Patients should be asked to
continue treatment but to seek medical advice if asthma symptoms remain
uncontrolled or worsen after initiation with DuoResp Spiromax.
There are no clinical study data on DuoResp Spiromax available in COPD
patients with a pre-bronchodilator FEV1 >50% predicted normal and with a
post-bronchodilator FEV1 <70% predicted normal (see section 5.1)
Paradoxical bronchospasm may occur, with an immediate increase in
wheezing and shortness of breath, after dosing. If the patient experiences
paradoxical bronchopasm DuoResp Spiromax should be discontinued
immediately, the patient should be assessed and an alternative therapy
instituted, if necessary. Paradoxical bronchopasm responds to a rapid-acting
inhaled bronchodilator and should be treated straightaway (see section 4.8).
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 section 4.8).
Visual disturbance may be reported with systemic and topical corticosteroid
use. If a patient presents with symptoms such as blurred vision or other
visual disturbances, the patient should be considered for referral to an
ophthalmologist for evaluation of possible causes which may include
cataract, glaucoma or rare diseases such as central serous chorioretinopathy
(CSCR) which have been reported after use of systemic and topical
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
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.
Effects on bone density
Potential effects on bone density should be considered, particularly in
patients on high doses for prolonged periods that have co-existing risk
factors for osteoporosis.
Long-term studies with inhaled budesonide 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 a budesonide/
formoterol fumarate dihydrate ﬁxed-dose combination at higher doses is
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 a budesonide/formoterol fumarate ﬁxed- dose combination
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 for a 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 hypothalamic pituitary adrenocortical (HPA) axis function
should be monitored regularly.
High dose corticosteroids
The 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 systematic steroids or inhaled budesonide
should not be stopped abruptly.
Transfer from oral therapy
During transfer from oral therapy to a budesonide/formoterol fumarate
ﬁxed-dose combination therapy, 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
To minimise the risk of oropharyngeal candida infection, the patient should
be instructed to rinse their mouth out with water after inhaling the dose.
If oropharyngeal thrush occurs, patients should also rinse their mouth with
water after the as-needed inhalations.
There are no clinical study data on Budesonide/Formoterol available in COPD
patients with a pre-bronchodilator FEV1 >50% predicted normal and with a
post-bronchodilator FEV1 <70% predicted normal (see section
Clinical studies and meta-analyses indicate that treatment of COPD with
inhaled corticosteroids may lead to an increased risk of pneumonia. However,
the absolute risk for budesonide is small. A meta-analysis of 11 COPD double
blind trials including 10,570 patients did not demonstrate a statistically
signiﬁcant increased risk of pneumonia in patients treated with budesonide
(with or without formoterol) compared to non-budesonide containing
treatments (placebo or formoterol). The incidence rate of pneumonia
reported as a serious adverse event was 1.9% per year on budesonide
containing treatments and 1.5% per year on non-budesonide containing
treatments. The pooled hazard ratio comparing all budesonide-containing
versus non-budesonide containing treatments was 1.15 (95% CI: 0.83, 1.57).
The pooled hazard ratio comparing budesonide/formoterol versus formoterol
or placebo was 1.00 (95% CI: 0.69, 1.44). A causal relationship with
budesonide-containing products has not been established.
Interaction with other medicinal products
Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4
inhibitors should be avoided (see section 4.5). If this is not possible the time
interval between administrations of the interacting medicinal products
should be as long as possible. In patients using potent CYP3A4 inhibitors,
a budesonide/formoterol fumarate ﬁxed-dose combination is not
Caution with special diseases
A ﬁxed-dose combination of budesonide and formoterol fumarate dihydrate
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
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.
Additional blood glucose controls should be considered in diabetic patients.
Potentially serious hypokalaemia may result from high doses of β
adrenoceptor agonists. Concomitant treatment of β
with medicinal products 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 β
Treatment with β
adrenoceptor agonists may result in an increase in blood
levels of insulin, free fatty acids, glycerol and ketone bodies.
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.
This medicinal product contains lactose. Patients with rare hereditary
problems of galactose intolerance, the Lapp lactase deﬁciency or
glucose-galactose malabsorption should not take this medicine. The
excipient lactose contains small amounts of milk proteins which may cause
Interaction with other medicinal products and other forms of
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 section 4.4).
The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased
plasma levels of concomitantly orally administered budesonide (single dose
3 mg) on average six-fold. 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
Co-treatment with CYP3A inhibitors, including cobicistat-containing products,
is expected to increase the risk of systemic side-effects. The combination
should be avoided unless the beneﬁt outweighs the increased risk of
systemic corticosteroid side-effects, in which case patients should be
monitored for systemic corticosteroid side-effects.
β adrenergic blockers can weaken or inhibit the effect of formoterol. A
ﬁxed-dose combination therapy of budesonide and formoterol fumarate
dihydrate should therefore not be given together with β 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 arrhythmias.
In addition L-Dopa, L-thyroxine, oxytocin and alcohol can impair cardiac
tolerance towards β
Concomitant treatment with monoamine oxidase inhibitors including
medicinal products 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 β adrenergic medicinal products and anticholinergic
medicinal products 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 medicinal products used in the treatment of asthma.
Interaction studies have only been performed in adults.
Fertility, pregnancy and lactation
For a ﬁxed-dose combination therapy of budesonide and formoterol
fumarate dihydrate 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 reactions in reproduction
studies at very high systemic exposure levels (see section 5.3).
Data on approximately 2000 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
section 5.3). This is not likely to be relevant for humans given recommended
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, a ﬁxed-dose combination therapy of budesonide and
formoterol fumarate dihydrate 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.
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 a
ﬁxed-dose combination therapy of budesonide and formoterol fumarate
dihydrate 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.
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 section 5.3).
Effects on ability to drive and use machines
DuoResp Spiromax has no or negligible inﬂuence on the ability to drive and
Summary of safety proﬁle
Since DuoResp Spiromax contains both budesonide and formoterol, the same
pattern of adverse reactions 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 adverse reactions
are pharmacologically predictable adverse reactions of β
agonist therapy, such as tremor and palpitations. These tend to be mild and
usually disappear within a few days of treatment. In a 3-year clinical trial
with budesonide in COPD, skin bruises and pneumonia occurred at a
frequency of 10% and 6%, respectively, compared with 4% and 3% in the
placebo group (p<0.001 and p<0.01, respectively).
Tabulated list of adverse reactions
Adverse reactions, which have been associated with budesonide or
formoterol, are given below and listed by system organ class and frequency.
Frequencies are deﬁned as: very common (≥1/10), common (≥1/100, <1/10),
uncommon (≥1/1,000, < 1/100), rare (≥1/10,000, < 1/1,000), very rare
(<1/10,000) and not known (cannot be estimated from the available data).
System Organ Class
Infections and infestations
Candida infections in the
oropharynx, pneumonia (in
Immune system disorders
Immediate and delayed
e.g. exanthema, urticaria,
Cushing´s syndrome, adrenal
retardation, decrease in bone
Metabolism and nutrition
hyperactivity, anxiety, sleep
changes (predominantly in
Nervous system disorders
Cataract and glaucoma
Vision, blurred (see also
Cardiac arrhythmias, e.g.
Angina pectoris. Prolongation
Variations in blood pressure
Respiratory, thoracic and
Mild irritation in the throat,
Skin and subcutaneous tissue
Musculoskeletal and connective
Description of selected adverse reactions
Candida infection in the oropharynx is due to active substance deposition.
Advising the patient to rinse the mouth out with water after each dose will
minimise the risk. Oropharyngeal Candida infection usually responds to
topical anti-fungal treatment without the need to discontinue the inhaled
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 bronchopasm responds to a rapid-acting
inhaled bronchodilator and should be treated straightaway. DuoResp
Spiromax should be discontinued immediately, the patient should be
assessed and an alternative therapy is instituted if necessary
(see section 4.4).
Systemic effects of inhaled corticosteroids may occur, particularly at high
doses prescribed for long 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
Treatment with β
adrenoceptor agonists may result in an increase in blood
levels of insulin, free fatty acids, glycerol and ketone bodies.
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.
An overdose of formoterol would likely lead to effects that are typical for β
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 overdose with budesonide, even in excessive doses, is not expected
to be a clinical problem. When used chronically in excessive doses, systemic
glucocorticosteroid effects, such as hypercorticism and adrenal suppression,
If DuoResp Spiromax therapy has to be withdrawn due to overdose of the
formoterol component of the medicinal product, provision of appropriate
inhaled corticosteroid therapy must be considered.
Mechanism of action and pharmacodynamic effects
DuoResp Spiromax contains formoterol and budesonide, which have different
modes of action and show additive effects in terms of reduction of asthma
exacerbations. The mechanisms of action of the two substances respectively
are discussed below.
Budesonide is a glucocorticosteroid which when inhaled has a dose-
dependent anti-inﬂammatory action in the airways, resulting in reduced
symptoms and fewer asthma exacerbations. Inhaled budesonide has less
severe adverse reactions than systemic corticosteroids. The exact
mechanism responsible for the anti-inﬂammatory effect of
glucocorticosteroids is unknown.
Formoterol is a selective β
adrenoceptor agonist that when inhaled results
in rapid and long-acting relaxation of bronchial smooth muscle in patients
with reversible airways obstruction. The bronchodilating effect is
dose-dependant, 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
Budesonide/formoterol maintenance therapy
Clinical studies in adults have shown that the addition of formoterol to
budesonide improved asthma symptoms and lung function, and reduced
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 β
adrenoceptor agonist as needed. There was no sign of
attenuation of the anti-asthmatic effect over time.
In a 12-week paediatric study, 85 children aged 6-11 years were treated
with a maintenance dose of Budesonide/Formoterol (2 inhalations of
80/4.5 micrograms/inhalation twice daily), and a short-acting β
needed. Lung function was improved, and the treatment was well tolerated
compared to the corresponding dose of Budesonide Turbuhaler.
In two 12-month studies, the effect on lung function and the rate of
exacerbation (deﬁned as courses of oral steroids and/or course of antibiotics
and/or hospitalisations) in patients with moderate to severe COPD was
evaluated. The inclusion criteria for both studies was pre-bronchodilator
FEV1<50% predicted normal. Median post-bronchodilator FEV1 at inclusion
in the trials was 42% predicted normal. The mean number of exacerbations
per year (as deﬁned above) was signiﬁcantly reduced with budesonide/
formoterol as compared with treatment with formoterol alone or placebo
(mean rate 1.4 compared with 1.8-1.9 in the placebo/formoterol group). The
mean number of days on oral corticosteroids/patient during the 12 months
was slightly reduced in the budesonide/formoterol group (7-8 days/patient/
year compared with 11-12 and 9-12 days in the placebo and formoterol
groups, respectively). For changes in lung-function parameters, such as FEV
budesonide/formoterol was not superior to treatment with formoterol alone.
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 ﬁxed-dose combination compared to the monoproducts.
The difference is considered not to have an impact on clinical safety.
There was no evidence of pharmacokinetic interactions between budesonide
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 (see paediatric
population sub-heading in section 4.2).
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 metabolism
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.
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 patients with liver disease.
Systemic exposure for both budesonide and formoterol correlates in a linear
fashion to administered dose.
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.
List of excipients
Lactose monohydrate (which contains milk proteins).
Please refer to expiry date on the outer carton.
After opening the foil wrap: 3 months.
Special precautions for storage
Do not store above 30 °C.
Keep the mouthpiece cover closed after removal of the foil wrap.
Nature and contents of container
The inhaler is white with a semi-transparent wine red mouthpiece cover.
The drug/mucosal contact parts of the inhaler are made of acrylonitrile
butadiene styrene (ABS), polyethylene (PE), and polypropylene (PP). Each
inhaler contains 60 doses and is foil-wrapped.
Pack sizes of 1, 2 or 3 inhalers.
Not all pack-sizes may be marketed.
Special precautions for disposal and other handling
No special requirements.
Norton (Waterford) Limited T/A
Teva Pharmaceuticals Ireland
Unit 27/35, IDA Industrial Park,
Cork Road, Waterford, Ireland.
DATE OF REVISION OF THE TEXT