BiResp Spiromax

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
BiResp Spiromax 160 micrograms / 4.5 micrograms inhalation powder 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each delivered dose (the dose that leaves the mouthpiece of the Spiromax) contains 160 micrograms of 
budesonide and  4.5 micrograms of formoterol fumarate dihydrate. 
 
This is equivalent to a metered dose of 200 micrograms budesonide and 6 micrograms of formoterol 
fumarate dihydrate. 
 
Excipient(s) with known effect:  
Each dose contains approximately 5 milligrams of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM  
 
Inhalation powder. 
 
White powder. 
 
White inhaler with a semi-transparent wine red mouthpiece cover.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
BiResp Spiromax is indicated in adults 18 years of age and older only.  
 
Asthma  
 
BiResp Spiromax is indicated in the regular treatment of asthma, where use of a combination (inhaled 
corticosteroid and long-acting β2 adrenoceptor agonist) is appropriate: 
 
-in patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting β2 
adrenoceptor agonists. 
or 
-in patients already adequately controlled on both inhaled corticosteroids and long-acting β2 adrenoceptor 
agonists. 
 
COPD 
 
Symptomatic treatment of patients with COPD with forced expiratory volume in 1 second (FEV1) < 70% 
predicted normal (post bronchodilator) and a history of repeated exacerbations, who have significant 
symptoms despite regular therapy with long-acting bronchodilators. 
 
 
 
 
 



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4.2 Posology and method of administration 
 
 
Posology 
 
Asthma 
 
BiResp Spiromax is not intended for the initial management of asthma.  
 
BiResp Spiromax is not an appropriate treatment for the adult patient with only mild asthma who is not 
adequately controlled with an inhaled corticosteroid and “as needed” inhaled short-acting β2 adrenoreceptor 
agonists.  
 
The dosage of BiResp Spiromax is individual and should be adjusted to the severity of the disease.  This 
should be considered not only when treatment with combination medicinal products is initiated but also 
when the maintenance dose is adjusted.  If an individual patient should require a combination of doses other 
than those available in the combination inhaler, appropriate doses of β2 adrenoceptor agonists and/or 
corticosteroids by individual inhalers should be prescribed. 
 
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of BiResp 
Spiromax. Patients should be reassessed regularly by their prescriber/health care provider so that the dose of 
BiResp Spiromax remains optimal. The dose should be titrated to the lowest dose at which effective control 
of symptoms is maintained.  
 
When it is appropriate to titrate down to a lower strength than is available for BiResp Spiromax, a change to 
an alternative fixed-dose combination of budesonide and formoterol fumarate containing a lower dose of the 
inhaled corticosteroid is required. When long-term control of symptoms is maintained with the lowest 
recommended dose, then the next step could include a test of inhaled corticosteroid alone.  
 
In usual practice when control of symptoms is achieved with the twice daily dose regimen with a lower 
strength product, titration to a lower effective dose could include once daily dosing when, in the opinion of 
the prescriber, a long-acting bronchodilator is required to maintain control rather than treatment with an 
inhaled corticosteroid alone. 
 
For BiResp Spiromax there are two treatment approaches: 
 
BiResp Spiromax maintenance therapy: BiResp Spiromax is taken as regular maintenance treatment with 
a separate rapid-acting bronchodilator reliever inhaler.   
 
BiResp Spiromax maintenance and reliever therapy: BiResp Spiromax is taken as regular maintenance 
treatment and as needed in response to symptoms.  
 
BiResp Spiromax maintenance therapy 
 
Patients should be advised to have their separate rapid-acting bronchodilator reliever inhaler available for 
rescue use at all times. 
 
Recommended doses: 
 
Adults (18 years and older):  1-2 inhalations twice daily.  Some patients may require up to a maximum of 4 
inhalations twice daily. 
 
 
Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition 
and warrants a reassessment of the asthma therapy. 
 



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BiResp Spiromax maintenance and reliever therapy 
 
Patients take a daily maintenance dose of BiResp Spiromax and in addition take BiResp Spiromax as needed 
in response to symptoms.  Patients should be advised to always have BiResp Spiromax available for rescue 
use.  
 
For patients taking BiResp Spiromax as reliever, preventative use of BiResp Spiromax for allergen- or 
exercise-induced bronchoconstriction should be discussed between physician and patient; the recommended 
use should take into consideration the frequency of need. In case of frequent need of bronchodilation without 
corresponding need for an increased dose of inhaled corticosteroids, an alternative reliever should be used.  
 
BiResp Spiromax maintenance and reliever therapy should especially be considered for patients with: 

• inadequate asthma control and in frequent need of a reliever inhaler.  
• asthma exacerbations in the past requiring medical intervention. 

 
Close monitoring for dose-related adverse reactions is needed in patients who frequently take high numbers 
of BiResp Spiromax as-needed inhalations. 
 
Recommended doses: 
 
Adults (18 years and older): The recommended maintenance dose is 2 inhalations per day, given either as 
one inhalation in the morning and evening or as 2 inhalations in either the morning or evening.  For some 
patients a maintenance dose of 2 inhalations twice daily may be appropriate.  Patients should take 1 
additional inhalation as needed in response to symptoms.  If symptoms persist after a few minutes, an 
additional inhalation should be taken.  Not more than 6 inhalations should be taken on any single occasion.  
 
A total daily dose of more than 8 inhalations is not normally needed; however, a total daily dose of up to 12 
inhalations could be used for a limited period.  Patients using more than 8 inhalations daily should be 
strongly recommended to seek medical advice.  They should be reassessed and their maintenance therapy 
should be reconsidered.  
 
COPD 
 
Recommended doses:  
 
Adults (18 years and older):  2 inhalations twice daily  
 
Special populations: 
 
Elderly patients (≥65 years old) 
 
There are no special dosing requirements for elderly patients.   
 
Patients with renal or hepatic impairment 
 
There are no data available for use of a fixed-dose combination of budesonide and formoterol fumarate 
dihydrate 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. 
 
Paediatric population  
 
The safety and efficacy of BiResp Spiromax in children, 12 years and younger and adolescents, 13 to 17 
years of age has not yet been established. No data are available.  
 
This medicinal product is not recommended for use in children and adolescents under the age of 18 years. 



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Method of administration 
 
Inhalation use. 
 
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).  
 
BiResp 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 leaflet.  
 
The use of BiResp Spiromax follows three 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 patients. 
 
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 BiResp Spiromax due to the lactose excipient. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or the excipient listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
General 
 
It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped 
abruptly. Complete withdrawal of inhaled corticosteroids should not be considered unless it is temporarily 
required to confirm diagnosis of asthma. 
 
If patients find the treatment ineffective, or exceed the highest recommended dose of BiResp 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 BiResp Spiromax (for 
asthma patients using BiResp Spiromax as maintenance and reliever therapy) or a separate rapid-acting 
bronchodilator (for asthma patients using BiResp Spiromax as maintenance therapy only). 
 



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Patients should be reminded to take their BiResp Spiromax maintenance dose as prescribed, even when 
asymptomatic.  The prophylactic use of BiResp Spiromax, e.g. before exercise, has not been studied.  The 
reliever inhalations of BiResp 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. 
 
Asthma symptoms 
 
Patients should be reassessed regularly by their prescriber/healthcare provider so that the dose of BiResp 
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 BiResp Spiromax.  When it is appropriate to titrate down to a lower strength than is 
available for BiResp 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 BiResp Spiromax during an exacerbation, or if they have significantly 
worsening or acutely deteriorating asthma.  
 
Serious asthma-related adverse reactions and exacerbations may occur during treatment with BiResp 
Spiromax. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms 
remain uncontrolled or worsen after initiation with BiResp Spiromax. 
 
There are no clinical study data on BiResp 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 BiResp 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 
 
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). 
 
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is 
regularly monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of 
inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained, if possible. The 
benefits of the corticosteroid therapy and the possible risks ofgrowth suppression must be carefully weighed. 
In addition consideration should be given to  referring the patient to a paediatric respiratory specialist. 
 
Limited data from long-term studies suggest that most children and adolescents treated with inhaled 
budesonide will ultimately achieve their adult target height. However, an initial small but transient reduction 
in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment. 
 
Visual disturbance 



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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 
corticosteroids. 
 
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 children at mean daily doses of 400 micrograms (metered 
dose) or in adults at daily doses of 800 micrograms (metered dose) have not shown any significant effects on 
bone mineral density. No information regarding the effect of a  budesonide/formoterol fumarate dihydrate 
fixed-dose combination at higher doses is available. 
 
Adrenal function 
 
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 
therapy.  
 
The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients 
transferring from oral steroids may remain at risk of impaired adrenal reserve 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 sometimes necessary. 
 
Oral infections 
 
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. 
 



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Pneumonia in patients with COPD 
 
An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been 
observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased 
risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all 
studies. 
 
There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk 
among inhaled corticosteroid products. 
 
Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the 
clinical features of such infections overlap with the symptoms of COPD exacerbations.  
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index 
(BMI) and severe COPD. 
 
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 recommended. 
 
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 failure. 
 
Caution should be observed when treating patients with prolongation of the QTc-interval. Formoterol itself 
may induce prolongation of the QTc-interval. 
 
The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent 
pulmonary tuberculosis, fungal and viral infections in the airways. 
 
Additional blood glucose controls should be considered in diabetic patients. 
 
β2 adrenoreceptor agonists 
 
Potentially serious hypokalaemia may result from high doses of β2 adrenoceptor agonists.  Concomitant 
treatment of β2 adrenoceptor agonists 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 β2 adrenoceptor agonist.   
 
Treatment with β2 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. 
 
Excipients 
 



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This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.  
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Pharmacokinetic interactions 
 
Potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, 
telithromycin, nefazodone and HIV protease inhibitors) are likely to markedly increase plasma levels of 
budesonide and concomitant use should be avoided. If this is not possible the time interval between 
administration of the inhibitor and budesonide should be as long as possible (see section 4.4). In patients 
using potent CYP3A4 inhibitors, a fixed-dose combination of budesonide and formoterol fumarate dihydrate 
maintenance and reliever therapy is not recommended. 
 
The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased plasma levels of concomitantly 
orally administered budesonide (single dose 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 1000 micrograms). 
 
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. 
 
Pharmacodynamic interactions 
 
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 β2 
sympathomimetics. 
 
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. 
 



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Paediatric population 
 
Interaction studies have only been performed in adults. 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
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 doses. 
 
Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for 
intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid 
receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.  
 
During pregnancy, 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. 
 
Breast-feeding 
 
Budesonide is excreted in breast milk.  However, at therapeutic doses no effects on the suckling child are 
anticipated.  It is not known whether formoterol passes into human breast milk.  In rats, small amounts of 
formoterol have been detected in maternal milk.  Administration of 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. 
 
Fertility 
 
There is no data available on the potential effect of budesonide on fertility. Animal reproduction studies with 
formoterol have shown a somewhat reduced fertility in male rats at high systemic exposure (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
BiResp Spiromax has no or negligible influence on the ability to drive and use machines. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Since BiResp 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 β2 adrenoceptor 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 



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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 Frequency Adverse reaction 
Infections and infestations Common  Candida infections in the oropharynx, pneumonia 

(in COPD patients) 
Immune system disorders Rare  Immediate and delayed hypersensitivity reactions, 

e.g. exanthema, urticaria, pruritus, dermatitis, 
angioedema and anaphylactic reaction  

Endocrine disorders Very rare  Cushing´s syndrome, adrenal suppression,  
growth retardation, decrease in bone mineral 
density  

Metabolism and nutrition 
disorders 

Rare  Hypokalaemia 
Very rare  Hyperglycaemia  

Psychiatric disorders Uncommon  Aggression, psychomotor hyperactivity, anxiety, 
sleep disorders 

Very rare  Depression, behavioural changes  
(predominantly in children)  

Nervous system disorders Common  Headache, tremor 
Uncommon  Dizziness 
Very rare  Taste disturbances 

Eye disorders Very rare Cataract and glaucoma 
Uncommon Vision, blurred (see also section 4.4) 

Cardiac disorders Common  Palpitations 
Uncommon  Tachycardia 
Rare  Cardiac arrhythmias, e.g. atrial fibrillation, 

supraventricular tachycardia, extrasystoles 
Very rare  Angina pectoris. Prolongation of QTc-interval 

Vascular disorders Very rare  Variations in blood pressure 
Respiratory, thoracic and 
mediastinal disorders 

Common  Mild irritation in the throat, coughing, Dysphonia 
including hoarseness 

Rare  Bronchospasm 
Very rare Paradoxical bronchospasm 

Gastrointestinal disorders Uncommon  Nausea 
Skin and subcutaneous 
tissue disorders 

Uncommon  Bruises 

Musculoskeletal and 
connective tissue disorders 

Uncommon  Muscle cramps 

 
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 corticosteroid. 
 
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-



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acting inhaled bronchodilator and should be treated straightaway. BiResp 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 sensitivity. 
 
Treatment with β2 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. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
An overdose of formoterol would likely lead to effects that are typical for β2 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, may appear. 
 
If BiResp 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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airway diseases, adrenergics and other drugs for 
obstructive airway diseases. 
 
ATC code: R03AK07 
 
Mechanism of action and pharmacodynamic effects 
 
BiResp Spiromax contains formoterol and budesonide, which have different modes of action and show 
additive effects in terms of reduction of asthma exacerbations.  The specific properties of budesonide and 
formoterol allow the combination to be used either as maintenance and reliever therapy, or as maintenance 
treatment of asthma.  The mechanisms of action of the two substances respectively are discussed below. 
 
Budesonide 
 
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 

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severe adverse reactions than systemic corticosteroids.  The exact mechanism responsible for the anti-
inflammatory effect of glucocorticosteroids is unknown. 
 
Formoterol 
 
Formoterol is a selective β2 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-dependent, with an onset of effect within 1-3 minutes.  The duration of effect is at least 12 hours after a 
single dose. 
 
 
Clinical efficacy and safety 
 
Asthma  
 
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 exacerbations.   
 
In two 12-week studies the effect on lung function of budesonide/formoterol was equal to that of the free 
combination of budesonide and formoterol, and exceeded that of budesonide alone.  All treatment arms used 
a short-acting β2 adrenoceptor agonist as needed.  There was no sign of attenuation of the anti-asthmatic 
effect over time. 
 
Two 12-week paediatric studies have been performed in which 265 children aged 6-11 years were treated 
with a maintenance dose of budesonide/formoterol (2 inhalations of 80 micrograms 
/4.5 micrograms/inhalation twice daily), and a short acting β2 adrenoceptor agonist as needed. In both 
studies, lung function was improved and the treatment was well tolerated compared to the corresponding 
dose of budesonide alone. 
 
Budesonide/formoterol maintenance and reliever therapy 
 
A total of 12076 asthma patients were included in 5 double-blind clinical studies (4447 were randomised to 
budesonide/formoterol maintenance and reliever therapy) for 6 or 12 months. Patients were required to be 
symptomatic despite use of inhaled glucocorticosteroids. 
 
Budesonide/formoterol maintenance and reliever therapy provided statistically significant and clinically 
meaningful reductions in severe exacerbations for all comparisons in all 5 studies.  This included a 
comparison with budesonide/formoterol at a higher maintenance dose with terbutaline as reliever (study 735) 
and budesonide/formoterol at the same maintenance dose with either formoterol or terbutaline as reliever 
(study 734) (see table below).  In Study 735, lung function, symptom control, and reliever use were similar 
in all treatment groups.  In Study 734, symptoms and reliever use were reduced and lung function improved, 
compared with both comparator treatments.  In the 5 studies combined, patients receiving 
budesonide/formoterol maintenance and reliever therapy used, on average, no reliever inhalations on 57% of 
treatment days.  There was no sign of development of tolerance over time. 
 
Overview of severe exacerbations in clinical studies 
 
Study 
No. 
Duration 

Treatment groups N Severe exacerbationsa 
Events Events/ 

patient-year 
Study 
735  

Budesonide/Formoterol Furmarate Dihydrate 
160/4.5 µg bd + as needed  

1103 125 0.23b 



14 

Study 
No. 
Duration 

Treatment groups N Severe exacerbationsa 
Events Events/ 

patient-year 
6 months Budesonide/Formoterol Furmarate Dihydrate 320/9 

µg bd + terbutaline 0.4 mg as needed 
1099 173 0.32  

Salmeterol/fluticasone 2 x 25/125 µg bd + terbutaline 
0.4 mg as needed 

1119 208 0.38  

Study 
734  
12 
months  

Budesonide/Formoterol Furmarate Dihydrate 
160/4.5 µg bd + as needed 

1107 194 0.19b 

Budesonide/Formoterol Furmarate Dihydrate 
160/4.5 µg bd + formoterol 4.5 µg as needed  

1137 296 0.29  

Budesonide/Formoterol Furmarate Dihydrate 
160/4.5 µg bd + terbutaline 0.4 mg as needed 

1138 377 0.37 

a Hospitalisation/emergency room treatment or treatment with oral steroids 
b Reduction in exacerbation rate is statistically significant (P value <0.01) for both comparisons 
 
In 2 other studies with patients seeking medical attention due to acute asthma symptoms, 
budesonide/formoterol provided rapid and effective relief of bronchoconstriction similar to salbutamol and 
formoterol. 
 
COPD 
 
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 severe COPD  
was evaluated. Median FEV1 at inclusion in the trials was 36% of 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 FEV1, budesonide/formoterol was not superior to treatment with formoterol alone. 
 
 
Peak Inspiratory Flow Rate through the Spiromax Device 
 
A randomised, open-label placebo study was performed in children and adolescents with asthma (aged 6-17 
years), adults with asthma (aged 18-45 years), adults with chronic obstructive pulmonary disease (COPD – 
aged >50 years) and healthy volunteers (aged 18-45 years) to evaluate the peak inspiratory flow rate (PIFR) 
and other related inhalation parameters following inhalation from a Spiromax device (containing placebo) 
compared with inhalation from an already marketed multi-dose dry powder inhaler device (containing 
placebo). The impact of enhanced training in dry powder inhaler inhalation technique on inhalation speed 
and volume was also assessed in these subject groups. The data from the study indicated that regardless of 
age and underlying disease severity, children, adolescents and adults with asthma as well as patients with 
COPD were able to able to achieve inspiratory flow rates through the Spiromax device that were similar to 
those generated through the marketed multi-dose dry powder inhaler device. The mean PIFR achieved by 
patients with asthma or COPD was over 60L/min, a flow rate at which both devices studied are known to 
deliver comparable amounts of drug to the lungs. Very few patients had PIFRs below 40L/min; when PIFRs 
were less than 40L/min there appeared to be no clustering by age or disease severity. 
 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The fixed-dose combination of budesonide and formoterol, and the corresponding monoproducts have been 
shown to be bioequivalent with regard to systemic exposure of budesonide and formoterol, respectively.  In 



15 

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 and formoterol. 
 
Pharmacokinetic parameters for the respective substances were comparable after the administration of 
budesonide and formoterol as monoproducts or as the fixed-dose combination.  For budesonide, AUC was 
slightly higher, rate of absorption more rapid and maximal plasma concentration higher after administration 
of the fixed combination.  For formoterol, maximal plasma concentration was similar after administration of 
the fixed combination. Inhaled budesonide is rapidly absorbed and the maximum plasma concentration is 
reached within 30 minutes after inhalation.  In studies, mean lung deposition of budesonide after inhalation 
via the powder inhaler ranged from 32% to 44% of the delivered dose.  The systemic bioavailability is 
approximately 49% of the delivered dose.  In children 6-16 years of age the lung deposition falls in the same 
range as in adults for the same given dose. The resulting plasma concentrations were not determined. 
 
Inhaled formoterol is rapidly absorbed and the maximum plasma concentration is reached within 10 minutes 
after inhalation.  In studies the mean lung deposition of formoterol after inhalation via the powder inhaler 
ranged from 28% to 49% of the delivered dose.  The systemic bioavailability is about 61% of the delivered 
dose.  
 
Distribution  
 
Plasma protein binding is approximately 50% for formoterol and 90% for budesonide.  Volume of 
distribution is about 4 L/kg for formoterol and 3 L/kg for budesonide.  Formoterol is inactivated via 
conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are seen 
mainly as inactivated conjugates).  Budesonide undergoes an extensive degree  (approximately 90%) of 
biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity.  The 
glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and 16-alfa-hydroxy-
prednisolone, is less than 1% of that of budesonide.  There are no indications of any metabolic interactions or 
any displacement reactions between formoterol and budesonide. 
 
Elimination 
 
The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination.  
After inhalation, 8% to 13% of the delivered dose of formoterol is excreted unmetabolised in the urine.  
Formoterol has a high systemic clearance (approximately 1.4 L/min) and the terminal elimination half-life 
averages 17 hours. 
 
Budesonide is eliminated via metabolism mainly catalysed by the enzyme CYP3A4.  The metabolites of 
budesonide are eliminated in urine as such or in conjugated form.  Only negligible amounts of unchanged 
budesonide have been detected in the urine.  Budesonide has a high systemic clearance (approximately 1.2 
L/min) and the plasma elimination half-life after i.v. dosing averages 4 hours. 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
 
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. 
 
BiResp Spiromax pharmacokinetic profile 
 
In pharmacokinetic studies with and without a charcoal blockage, BiResp Spiromax was evaluated by 
comparing it with an alternative authorised fixed-dose combination inhaled product containing the same 
active substances, budesonide and formoterol and has been shown to be equivalent in both systemic exposure 
(safety) and pulmonary deposition (efficacy). 
 
Linearity/non-linearity  



16 

Systemic exposure for both budesonide and formoterol correlates in a linear fashion to administered dose. 
 
5.3 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. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
After opening the foil wrap: 6 months.  
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Keep the mouthpiece cover closed after removal of the foil wrap.  
 
6.5 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 120 doses and is foil-wrapped.   
 
Pack sizes of 1, 2 or 3 inhalers. 
 
Not all pack-sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
Swensweg 5, 2031GA Haarlem 



17 

The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/921/001 
EU/1/14/921/002 
EU/1/14/921/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28th April 2014 
Date of latest renewal: 8th April 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product  is available on the website of the European Medicines 
Agency http://www.ema.europa.com 
 
 

http://www.ema.europa.com/


18 

1. NAME OF THE MEDICINAL PRODUCT 
 
BiResp Spiromax 320 micrograms/9 micrograms inhalation powder 
 
 
2. 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 fumarate dihydrate.  
 
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. 
 
 
3. PHARMACEUTICAL FORM  
 
Inhalation powder. 
 
White powder. 
 
White inhaler with a semi-transparent wine red mouthpiece cover.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
BiResp Spiromax is indicated in adults 18 years of age and older only.  
 
Asthma 
BiResp Spiromax is indicated in the regular treatment of asthma, where use of a combination (inhaled 
corticosteroid and long-acting β2 adrenoceptor agonist) is appropriate: 
 
- in patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting β2 
adrenoceptor agonists. 
or 
- in patients already adequately controlled on both inhaled corticosteroids and long-acting β2 adrenoceptor 
agonists. 
 
COPD 
 
Symptomatic treatment of patients with COPD with forced expiratory volume in 1 second (FEV1) < 70% 
predicted normal (post bronchodilator) and a history of repeated exacerbations, who have significant 
symptoms despite regular therapy with long-acting bronchodilators. 
 
4.2 Posology and method of administration 
 
 
Posology 
 
Asthma 



19 

 
BiResp Spiromax is not intended for the initial management of asthma. 
 
BiResp Spiromax is not an appropriate treatment for the adult patient with only mild asthma who is not 
adequately controlled with an inhaled corticosteroid and “as needed” inhaled short-acting β2 adrenoreceptor 
agonists.   
 
The dosage of BiResp Spiromax is individual and should be adjusted to the severity of the disease.  This 
should be considered not only when treatment with combination medicinal products is initiated but also 
when the maintenance dose is adjusted.  If an individual patient should require a combination of doses other 
than those available in the combination inhaler, appropriate doses of β2 adrenoceptor agonists and/or 
corticosteroids by individual inhalers should be prescribed. 
 
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of BiResp 
Spiromax.  Patients should be reassessed regularly by their prescriber/health care provider so that the dose of 
BiResp Spiromax remains optimal. The dose should be titrated to the lowest dose at which effective control 
of symptoms is maintained.  
 
When it is appropriate to titrate down to a lower strength than is available for BiResp Spiromax, a change to 
an alternative fixed–dose combination of budesonide and formoterol fumarate containing a lower dose of the 
inhaled corticosteroid is required. When long-term control of symptoms is maintained with the lowest 
recommended dose, then the next step could include a test of inhaled corticosteroid alone. 
 
In usual practice when control of symptoms is achieved with the twice daily dose regimen with a lower 
strength product, titration to a lower effective dose could include once daily dosing when, in the opinion of 
the prescriber, a long-acting bronchodilator is required to maintain control rather than treatment with an 
inhaled corticosteroid alone. 
 
Patients should be advised to have their separate rapid-acting bronchodilator reliever inhaler available for 
rescue use at all times. 
 
Recommended doses:  
 
Adults (18 years and older): 1 inhalation twice daily.  Some patients may require up to a maximum of 2 
inhalations twice daily. 
 
 
Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition 
and warrants a reassessment of the asthma therapy. 
 
BiResp Spiromax 320 micrograms/9 micrograms should be used as maintenance therapy only.  A lower 
strength of BiResp Spiromax is available for the maintenance and reliever therapy regimen. 
 
COPD 
 
Recommended doses: 
 
Adults (18 years and older):  
 
1 inhalation twice daily 
 
Special populations: 
 
Elderly patients (≥65 years old) 
 
There are no special dosing requirements for elderly patients.   
 



20 

Patients with renal or hepatic impairment 
 
There are no data available for use of a fixed-dose combination of budesonide and formoterol fumarate 
dihydrate 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. 
 
Paediatric population 
 
The safety and efficacy of BiResp Spiromax in children, 12 years and younger and adolescents, 13 to 17 
years of age has not yet been established. No data are available.  
 
This medicinal product is not recommended for use in children and adolescents under the age of 18 years. 
 
Method of administration 
 
Inhalation use. 
 
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).  
 
BiResp 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 leaflet.  
 
The use of BiResp Spiromax follows three 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 patients. 
 
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 BiResp Spiromax due to the lactose excipient. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or the excipient listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
General 
 
It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped 
abruptly. 
 



21 

If patients find the treatment ineffective, or exceed the highest recommended dose of BiResp 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 BiResp Spiromax (for 
asthma patients using BiResp Spiromax as maintenance and reliever therapy) or a separate rapid-acting 
bronchodilator (for asthma patients using BiResp Spiromax as maintenance therapy only). 
 
Patients should be reminded to take their BiResp Spiromax maintenance dose as prescribed, even when 
asymptomatic.  The prophylactic use of BiResp Spiromax, e.g. before exercise, has not been studied.  The 
reliever inhalations of BiResp 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. 
 
Asthma symptoms 
 
Patients should be reassessed regularly by their prescriber/healthcare provider so that the dose of BiResp 
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 BiResp Spiromax.  When it is appropriate to titrate down to a lower strength than is 
available for BiResp 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 BiResp Spiromax during an exacerbation, or if they have significantly 
worsening or acutely deteriorating asthma.  
 
Serious asthma-related adverse reactions and exacerbations may occur during treatment with BiResp 
Spiromax. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms 
remain uncontrolled or worsen after initiation with BiResp Spiromax. 
 
There are no clinical study data on BiResp 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 BiResp 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 
 
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). 
 
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is 
regularly monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of 
inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained, if possible. The 



22 

benefits of the corticosteroid therapy and the possible risks of growth suppression must be carefully weighed. 
In addition consideration should be given to  referring the patient to a paediatric respiratory specialist. 
 
Limited data from long-term studies suggest that most children and adolescents treated with inhaled 
budesonide will ultimately achieve their adult target height. However, an initial small but transient reduction 
in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment. 
 
Visual disturbance 
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 
corticosteroids. 
 
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 children at mean daily doses of 400 micrograms (metered 
dose) or in adults at daily doses of 800 micrograms (metered dose) have not shown any significant effects on 
bone mineral density. No information regarding the effect of a budesonide/formoterol fumarate dihydrate 
fixed-dose combination at higher doses is available. 
 
Adrenal function 
 
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 therapy.  
 
The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients 
transferring from oral steroids may remain at risk of impaired adrenal reserve 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, 



23 

symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary 
increase in the dose of oral glucocorticosteroids is sometimes necessary. 
 
Oral infections 
 
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. 
 
Pneumonia in patients with COPD 
 
An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been 
observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased 
risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all 
studies. 
 
There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk 
among inhaled corticosteroid products. 
 
Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the 
clinical features of such infections overlap with the symptoms of COPD exacerbations.  
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index 
(BMI) and severe COPD. 
 
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 recommended. 
 
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 failure. 
 
Caution should be observed when treating patients with prolongation of the QTc-interval. Formoterol itself 
may induce prolongation of the QTc-interval. 
 
The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent 
pulmonary tuberculosis, fungal and viral infections in the airways. 
 
Additional blood glucose controls should be considered in diabetic patients. 
 
β2 adrenoreceptor agonists 
 
Potentially serious hypokalaemia may result from high doses of β2 adrenoceptor agonists.  Concomitant 
treatment of β2 adrenoceptor agonists 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 β2 adrenoceptor agonist.   
 
Treatment with β2 adrenoceptor agonists may result in an increase in blood levels of insulin, free fatty acids, 
glycerol and ketone bodies. 



24 

 
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. 
 
Excipients 
 
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Pharmacokinetic interactions 
 
Potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, 
telithromycin, nefazodone and HIV protease inhibitors) are likely to markedly increase plasma levels of 
budesonide and concomitant use should be avoided. If this is not possible the time interval between 
administration of the inhibitor and budesonide should be as long as possible (see 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 1000 micrograms). 
 
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.1  
 
Pharmacodynamic interactions 
 
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 β2 
sympathomimetics. 
 
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. 



25 

 
Budesonide and formoterol have not been observed to interact with any other medicinal products used in the 
treatment of asthma. 
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
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 doses. 
 
Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for 
intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid 
receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.  
 
During pregnancy, 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. 
 
Breast-feeding 
 
Budesonide is excreted in breast milk.  However, at therapeutic doses no effects on the suckling child are 
anticipated.  It is not known whether formoterol passes into human breast milk.  In rats, small amounts of 
formoterol have been detected in maternal milk.  Administration of 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. 
 
Fertility 
 
There is no data available on the potential effect of budesonide on fertility. Animal reproduction studies with 
formoterol have shown a somewhat reduced fertility in male rats at high systemic exposure (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
BiResp Spiromax has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Since BiResp 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 β2 adrenoceptor agonist therapy, such as tremor and 



26 

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 Frequency Adverse reaction 
Infections and infestations Common  Candida infections in the oropharynx, pneumonia 

(in COPD patients) 
Immune system disorders Rare  Immediate and delayed hypersensitivity reactions, 

e.g. exanthema, urticaria, pruritus, dermatitis, 
angioedema and anaphylactic reaction  

Endocrine disorders Very rare  Cushing´s syndrome, adrenal suppression, growth 
retardation, decrease in bone mineral density  

Metabolism and nutrition 
disorders 

Rare  Hypokalaemia 
Very rare  Hyperglycaemia  

Psychiatric disorders Uncommon  Aggression, psychomotor hyperactivity, anxiety, 
sleep disorders 

Very rare  Depression, behavioural changes 
(predominantly in children)  

Nervous system disorders Common  Headache, tremor 
Uncommon  Dizziness 
Very rare  Taste disturbances 

Eye disorders Very rare Cataract and glaucoma 
Uncommon Vision, blurred (see also section 4.4) 

Cardiac disorders Common  Palpitations 
Uncommon  Tachycardia 
Rare  Cardiac arrhythmias, e.g. atrial fibrillation, 

supraventricular tachycardia, extrasystoles 
Very rare  Angina pectoris. Prolongation of QTc-interval 

Vascular disorders Very rare  Variations in blood pressure 
Respiratory, thoracic and 
mediastinal disorders 

Common  Mild irritation in the throat, coughing, Dysphonia 
including hoarseness 

Rare  Bronchospasm 
Very rare Paradoxical bronchospasm 

Gastrointestinal disorders Uncommon  Nausea 
Skin and subcutaneous 
tissue disorders 

Uncommon  Bruises 

Musculoskeletal and 
connective tissue disorders 

Uncommon  Muscle cramps 

 
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 corticosteroid. 
 



27 

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. BiResp 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 sensitivity. 
 
Treatment with β2 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. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
An overdose of formoterol would likely lead to effects that are typical for β2 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, may appear. 
 
If BiResp 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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airway diseases, adrenergics and other drugs for 
obstructive airway diseases. 
 
ATC code: R03AK07 
 
Mechanism of action and pharmacodynamic effects 
 
BiResp 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 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


28 

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 
 
Formoterol is a selective β2 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-dependent, with an onset of effect within 1-3 minutes.  The duration of effect is at least 12 hours after a 
single dose. 
 
Clinical efficacy and safety 
 
Asthma  
 
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 exacerbations.   
 
In two 12-week studies the effect on lung function of budesonide/formoterol was equal to that of the free 
combination of budesonide and formoterol, and exceeded that of budesonide alone.  All treatment arms used 
a short-acting β2 adrenoceptor agonist as needed.  There was no sign of attenuation of the anti-asthmatic 
effect over time. 
 
Two 12-week paediatric studies have been performed in which 265 children aged 6-11 years were treated 
with a maintenance dose of budesonide/formoterol (2 inhalations of 
80 micrograms/4.5 micrograms/inhalation twice daily), and a short acting β2 adrenoceptor agonist as needed. 
In both studies, lung function was improved and the treatment was well tolerated compared to the 
corresponding dose of budesonide alone. 
 
COPD 
 
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 severe COPD was evaluated. 
Median FEV1 at inclusion in the trials was 36% of 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 FEV1, 
budesonide/formoterol was not superior to treatment with formoterol alone. 
 
Peak Inspiratory Flow Rate through the Spiromax Device  
 
A randomised, open-label placebo study was performed in children and adolescents with asthma (aged 6-17 
years), adults with asthma (aged 18-45 years), adults with chronic obstructive pulmonary disease (COPD – 
aged >50 years) and healthy volunteers (aged 18-45 years) to evaluate the peak inspiratory flow rate (PIFR) 
and other related inhalation parameters following inhalation from a  Spiromax device (containing placebo) 
compared with inhalation from an already marketed multi-dose dry powder inhaler device (containing 
placebo). The impact of enhanced training in dry powder inhaler inhalation technique on inhalation speed 
and volume was also assessed in these subject groups. The data from the study indicated that regardless of 
age and underlying disease severity, children, adolescents and adults with asthma as well as patients with 
COPD were able to able to achieve inspiratory flow rates through the Spiromax device that were similar to 
those generated through the marketed multi-dose dry powder inhaler device. The mean PIFR achieved by 
patients with asthma or COPD was over 60L/min, a flow rate at which both devices studied are known to 



29 

deliver comparable amounts of drug to the lungs. Very few patients had PIFRs below 40L/min; when PIFRs 
were less than 40L/min there appeared to be no clustering by age or disease severity. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The fixed-dose combination of budesonide and formoterol, and the corresponding monoproducts have been 
shown to be bioequivalent with regard to systemic exposure of budesonide and formoterol, respectively.  In 
spite of this, a small increase in cortisol suppression was seen after administration of 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 and formoterol. 
 
Pharmacokinetic parameters for the respective substances were comparable after the administration of 
budesonide and formoterol as monoproducts or as the fixed-dose combination.  For budesonide, AUC was 
slightly higher, rate of absorption more rapid and maximal plasma concentration higher after administration 
of the fixed combination.  For formoterol, maximal plasma concentration was similar after administration of 
the fixed combination. Inhaled budesonide is rapidly absorbed and the maximum plasma concentration is 
reached within 30 minutes after inhalation.  In studies, mean lung deposition of budesonide after inhalation 
via the powder inhaler ranged from 32% to 44% of the delivered dose.  The systemic bioavailability is 
approximately 49% of the delivered dose.  In children 6-16 years of age the lung deposition falls in the same 
range as in adults for the same given dose. The resulting plasma concentrations were not determined. 
 
Inhaled formoterol is rapidly absorbed and the maximum plasma concentration is reached within 10 minutes 
after inhalation.  In studies the mean lung deposition of formoterol after inhalation via the powder inhaler 
ranged from 28% to 49% of the delivered dose.  The systemic bioavailability is about 61% of the delivered 
dose.  
 
Distribution  
 
Plasma protein binding is approximately 50% for formoterol and 90% for budesonide.  Volume of 
distribution is about 4 L/kg for formoterol and 3 L/kg for budesonide.  Formoterol is inactivated via 
conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are seen 
mainly as inactivated conjugates).  Budesonide undergoes an extensive degree (approximately 90%) of 
biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity.  The 
glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and 16-alfa-hydroxy-
prednisolone, is less than 1% of that of budesonide.  There are no indications of any metabolic interactions or 
any displacement reactions between formoterol and budesonide. 
 
Elimination 
 
The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination.  
After inhalation, 8% to 13% of the delivered dose of formoterol is excreted unmetabolised in the urine.  
Formoterol has a high systemic clearance (approximately 1.4 L/min) and the terminal elimination half-life 
averages 17 hours. 
 
Budesonide is eliminated via metabolism mainly catalysed by the enzyme CYP3A4.  The metabolites of 
budesonide are eliminated in urine as such or in conjugated form.  Only negligible amounts of unchanged 
budesonide have been detected in the urine.  Budesonide has a high systemic clearance (approximately 1.2 
L/min) and the plasma elimination half-life after i.v. dosing averages 4 hours. 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
 
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. 
 



30 

 
BiResp Spiromax pharmacokinetic profile 
 
In pharmacokinetic studies with and without a charcoal blockage, BiResp Spiromax was evaluated by 
comparing it with an alternative authorised fixed-dose combination inhaled product containing the same 
active substances, budesonide and formoterol and has been shown to be equivalent in both systemic exposure 
(safety) and pulmonary deposition (efficacy). 
 
Linearity/non-linearity  
Systemic exposure for both budesonide and formoterol correlates in a linear fashion to administered dose. 
 
5.3 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. 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
After opening the foil wrap: 6 months.  
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Keep the mouthpiece cover closed after removal of the foil wrap.  
 
6.5 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. 
 
6.6 Special precautions for disposal and other handling 
 



31 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.. 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
Swensweg 5, 2031GA Haarlem 
The Netherlands 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/921/004 
EU/1/14/921/005 
EU/1/14/921/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28th April 2014 
Date of latest renewal: 8th April 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
Detailed information on this medicinal product  is available on the website of the European Medicines 
Agency http://www.ema.europa.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

http://www.ema.europa.com/


32 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 



33 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturers responsible for batch release 
 
Norton (Waterford) Limited T/A Teva Pharmaceuticals Ireland 
Unit 27/35 IDA Industrial Park 
Cork Road 
Waterford 
Republic of Ireland 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5  
NL-2031 GA Haarlem 
The Netherlands 
 
The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal products subject to medical prescription. 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

• Periodic safety update reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are set out in 
the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached.  

 
 

 
 



34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BiResp Spiromax 160 micrograms /4.5 micrograms inhalation powder 
 
budesonide / formoterol fumarate dihydrate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
 
Side panel: Each delivered dose contains 160 micrograms of budesonide and 4.5 micrograms of formoterol 
fumarate dihydrate. 
 
This is equivalent to a metered dose of 200 micrograms of budesonide and 6 micrograms of formoterol 
fumarate dihydrate.  
 
Front panel: This delivered dose is equivalent to a metered dose of 200 micrograms of budesonide and 
6 micrograms of formoterol fumarate dihydrate.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information   
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder 
1 inhaler containing 120 doses. 
2 inhalers each containing 120 doses.   
3 inhalers each containing 120 doses.  
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
Read the package leaflet before use. 
Inhalation use. 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Front panel: Not for use in children and adolescents. 
 
Side panel: For use in adults 18 years of age and older only.  
Not for use in children or adolescents under 18 years of age.  



37 

 
8. EXPIRY DATE 
 
EXP 
Use the product within 6 months of removing from foil wrapping. 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. Keep the mouthpiece cover closed after the removal of foil wrap.   
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/921/001 
EU/1/14/921/002 
EU/1/14/921/003 
 
13. BATCH NUMBER 
 
 Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BiResp Spiromax 160 mcg/4.5 mcg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
  



38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
FOIL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BiResp Spiromax 160 micrograms / 4.5 micrograms inhalation powder 
 
budesonide/ formoterol fumarate dihydrate  
 
Inhalation use. 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
 Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Contains 1 inhaler. 
 
6. OTHER 
 
Keep the mouthpiece cover closed and use within 6 months of removing from foil wrapping. 
 
Teva Pharma B.V.  
 
 
  



39 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
INHALER 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BiResp Spiromax 160 mcg/4.5 mcg  inhalation powder 
 
budesonide/formoterol fumarate dihydrate  
 
Inhalation use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
 Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
120 doses 
 
6. OTHER 
 
Start  
 
Teva Pharma B.V.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
BiResp Spiromax 320 micrograms/9 micrograms inhalation powder 
 
budesonide/formoterol fumarate dihydrate  
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Side panel: Each delivered 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 
fumarate dihydrate.  
 
Front panel: This delivered dose is equivalent to a metered dose of 400 micrograms of budesonide and 
12 micrograms of formoterol fumarate dihydrate.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information   
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder 
1 inhaler containing 60 doses. 
2 inhalers each containing 60 doses. 
3 inhalers each containing 60 doses. 
   
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
Read the package leaflet before use. 
Inhalation use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Front panel: Not for use in children and adolescents. 
 
Side panel: For use in adults 18 years of age and older only.  
Not for use in children or adolescents under 18 years of age.  
 



41 

 
 
8. EXPIRY DATE 
 
EXP 
Use the product within 6 months of removing from foil wrapping. 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. Keep the mouthpiece cover closed after the removal of foil wrap. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/921/004 
EU/1/14/921/005 
EU/1/14/921/006 
 
 
13. BATCH NUMBER 
 
 Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
BiResp Spiromax 320  mcg/9  mcg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
  



42 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
FOIL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BiResp Spiromax 320 micrograms/9 micrograms inhalation powder 
 
budesonide/formoterol fumarate dihydrate  
 
Inhalation use. 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Contains 1 inhaler. 
 
6. OTHER 
 
Keep the mouthpiece cover closed and use within 6 months of removing from foil wrapping. 
 
Teva Pharma B.V.  
 
 
  



43 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
INHALER 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
BiResp Spiromax 320 mcg/9 mcg inhalation powder 
 
budesonide/formoterol fumarate dihydrate  
 
Inhalation use. 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
60 doses 
 
6. OTHER 
 
Start  
 
Teva Pharma B.V.  
 
 

  



44 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



45 

Package leaflet: Information for the patient 
 

BiResp Spiromax 160 micrograms/4.5 micrograms, inhalation powder 
 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 nurse. 
- 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 BiResp Spiromax is and what it is used for 
2. What you need to know before you use BiResp Spiromax 
3. How to use BiResp Spiromax 
4. Possible side effects 
5. How to store BiResp Spiromax 
6. Contents of the pack and other information 
 
 
1. What BiResp Spiromax is and what it is used for 
 
BiResp 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 more 
easily.  

• Formoterol fumarate dihydrate belongs to a group of medicines called ‘long-acting β2 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. 

 
BiResp Spiromax is indicated for use  in adults 18 years of age and older only.  
BiResp Spiromax is NOT indicated for use in children 12 years of age and younger or adolescents 13 
to 17 years of age.  
 
Your doctor has prescribed this medicine to treat asthma or chronic obstructive pulmonary disease (COPD).  
 
Asthma 
BiResp Spiromax can be prescribed for asthma in two different ways. 
 
a)  You may be prescribed two asthma inhalers: BiResp Spiromax together with a separate ‘reliever 
inhaler’ such as salbutamol. 
• Use BiResp 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.  
 
b)  You may be prescribed BiResp Spiromax  as your only asthma inhaler. 
• Use BiResp Spiromax every day.  This helps to prevent asthma symptoms such as breathlessness and 

wheezing from occurring.  
• Use BiResp Spiromax when you  need to take extra inhalations or puffs for relief of  asthma symptoms, 

to make it easier to breathe again and if agreed with the doctor also to prevent asthma symptoms from 
happening (for example, when exercising or on exposure to allergens). They do not need a separate 
inhaler for this.  



46 

 
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. BiResp Spiromax 
can also be used to treat the symptoms of severe COPD in adults only.  
 
 
2. What you need to know before you use BiResp Spiromax  
 
Do not use BiResp 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 BiResp Spiromax if 
• 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 BiResp 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 BiResp Spiromax. 
 
Your doctor may consider adding steroid tablets to your usual treatment if you have an illness such as a chest 
infection or before an operation. 
 
Contact your doctor if you experience blurred vision or other visual disturbances. 
 
Children and adolescents 
This medicine should not be used in children or adolescents under the age of 18 years. 
 
Other medicines and BiResp 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 following medicines: 
• β blockers (such as atenolol or propranolol for high blood pressure or a heart condition), including 

eyedrops (such as timolol for glaucoma). 
• Oxytocin which is given to pregnant women to induce labour 
• Medicines for a fast or uneven heartbeat (such as quinidine, disopyramide, procinamide and terfanadine). 
• 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). 



47 

• Tricyclic antidepressants (such as amitriptyline) and the antidepressant nefazodone. 
• Antidepressant 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 and prochlorperazine).  
• Medicines called ‘HIV protease inhibitors’ (such as ritonavir) to treat HIV infection. 
• 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 BiResp 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 
BiResp 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 BiResp Spiromax - do NOT use this medicine 
unless your doctor tells you to.  

• If you get pregnant while using BiResp Spiromax, do NOT stop using BiResp Spiromax but talk to your 
doctor immediately. 

 
 
Driving and using machines 
 
BiResp Spiromax is not likely to affect your ability to drive or to use tools or machines. 
 
BiResp 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.   
 
 
3.  How to use BiResp Spiromax 

 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor, 
pharmacist or nurse if you are not sure. 
 

• It is important to use BiResp Spiromax every day, even if you have no asthma or COPD symptoms at 
the time.  

• If you are using BiResp Spiromax for asthma, your doctor will want to regularly check your 
symptoms.  

 
Asthma  
BiResp Spiromax can be prescribed for asthma in two different ways. The amount of BiResp Spiromax to 
use and when to use it depends on how it has been prescribed for you.  
 
• If you have been prescribed BiResp Spiromax and a separate reliever inhaler, read the section called (A) 

Using BiResp Spiromax and a separate ‘reliever inhaler’.  
• If you have been prescribed BiResp Spiromax as your only inhaler, read the section called (B) Using 

BiResp Spiromax  as your only asthma inhaler. 
 
(A) Using BiResp Spiromax and a separate ‘reliever inhaler’  



48 

Use your BiResp Spiromax every day. This helps to prevent asthma symptoms from occurring. 
 
Recommended dose:  
Adults (18 years and older) 
1 or 2 inhalations (actuations), twice a day, taken in the morning and in the evening.  
Your doctor may increase this to 4 inhalations, twice a day. 
If your symptoms are well controlled, your doctor may ask you to take your medicine once a day. 
 
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 BiResp 
Spiromax, your doctor may prescribe an alternative inhaler containing the same active substances as your 
BiResp 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 BiResp Spiromax to treat these asthma symptoms. 
 
(B) Using BiResp Spiromax as your only asthma inhaler 
 
Only use BiResp Spiromax in this way if your doctor has told you to.  
 
Use your BiResp Spiromax every day. This helps to prevent asthma symptoms from occurring. 
  
Recommended dose  
Adults (18 years and older) 
 
1 inhalation in the morning and 1 inhalation in the evening 
or 
2 inhalations in the morning  
or 
2 inhalations in the evening. 
 
Your doctor may increase this to 2 inhalations twice a day.  
 
Also use BiResp Spiromax as a ‘reliever inhaler’ to treat asthma symptoms when they happen and to 
prevent asthma symptoms from happening (for example,when exercising or on exposure to allergens).  
• If you get asthma symptoms, take 1  inhalation and wait a few minutes.  
• If you do not feel better, take another inhalation.  
• Do not take more than 6 inhalations at a single time. 
 
Always keep your BiResp Spiromax with you and use it to relieve sudden attacks of breathlessness and 
wheezing. 
 
A total daily dose of more than 8 inhalations is not normally needed.  However, your doctor may allow you 
to take up to 12 inhalations a day for a limited period.  
 
If you regularly need to use 8 or more inhalations a day, make an appointment to see your doctor.  They may 
need to change your treatment.  
 
Do NOT use more than 12 inhalations in total in 24 hours. 
 
If you are doing exercise and you get asthma symptoms, use BiResp Spiromax as described here.  However, 
do not use BiResp Spiromax just before exercise to stop asthma symptoms from happening. 
 
 
Chronic Obstructive Pulmonary Disease (COPD) 



49 

 
Recommended dose: 
Adults (18 years and older): 
2 inhalations twice a day, taken in the morning and in the evening 
 
Your doctor may also prescribe another bronchodilator medicine, for example an anticholinergic (such as 
tiotropium or ipratropium bromide) for your COPD disease. 
 
Preparing your new BiResp Spiromax  
 
Before using your BiResp 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 120 inhalations in the inhaler. 
• Write the date you opened the foil pouch on the label of the inhaler. 
• Do not shake your inhaler before use. 

 
How to take an inhalation 
Every time you need to take an inhalation, follow the instructions below. 
 
1.    Hold your inhaler with the semi-transparent wine red mouthpiece cover at the bottom. 
 

 
 
2. 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. 
 

  
 
3. Breathe out gently (as far as is comfortable). Do not breathe out through your inhaler. 
4.   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. 
  



50 

 
 
5.   Remove your inhaler from your mouth.  You may notice a taste when you take your inhalation.  
6.  Hold your breath for 10 seconds or as long as you comfortably can. 
 
 
7.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 120 

inhalations when it is full and ending with 0 (zero) inhalations when it is empty.  
 

 
 



51 

• 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. 

 
 
Note:  

• 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 one inhalation.  

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 BiResp Spiromax, you should continue to use 
BiResp Spiromax  but go to see your doctor as soon as possible, as you may need additional treatment. 
 
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 treatment immediately. 
 
Once your asthma is well controlled your doctor may consider it appropriate to gradually reduce the dose of 
BiResp Spiromax. 
 
If you use more BiResp 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 advice. 
 
If you use more BiResp Spiromax than you should, contact your doctor, pharmacist or nurse for advice. 
The most common symptoms that may occur after when you use more BiResp Spiromax than you should are 
trembling, headache or a rapid heartbeat.  
 
If you forget to use BiResp 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 usual time.  
 
If you become wheezy or breathless, or develop any other symptoms of an asthma attack, use your ‘reliever 
inhaler’, then seek medical advice.  
 
If you stop using BiResp 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. 
 
 
4. 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 BiResp Spiromax and talk to your doctor 
immediately:  
 
Rare side effects: may affect up to 1 in 1,000 people 
 



52 

• 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 BiResp 
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 BiResp 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. 
• Headache. 
• Pneumonia (infection to the lung) in COPD patients. 

 
Tell your doctor if you have any of the following while taking BiResp 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.  
• Disturbed sleep. 
• Feeling dizzy. 
• Nausea (feeling sick).  
• Fast heartbeat.  
• Bruising of the skin. 
• Muscle cramps 
• Blurred vision.  

 
Rare:  
• Low levels of potassium in your blood.  
• Uneven heartbeat. 

 
Very rare:  
• Depression.  
• 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.  



53 

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.  
 
You can also report side effects directly via the national reporting system listed in Appendix V. By reporting 
side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store BiResp 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 25 oC.  Keep the mouthpiece cover closed after removal of the foil wrapping. 
• Use within 6 months of removing from the foil wrapping. Use the label on the inhaler to write down 

the date you open the foil pouch. 
• 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. 
 
 
6. Contents of the pack and other information 
 
What BiResp Spiromax contains  
- The active substances are budesonide and formoterol fumarate dihydrate. Each delivered (inhaled) dose 

contains 160 micrograms of budesonide and 4.5 micrograms of formoterol fumarate dihydrate. This is 
equivalent to a metered dose of 200 micrograms of budesonide and 6 micrograms of formoterol fumarate 
dihydrate.  

- The other ingredient is lactose monohydrate (see section 2 under ‘BiResp Spiromax contains lactose’) 
 
What BiResp Spiromax looks like and contents of the pack 
 
BiResp Spiromax is an inhalation powder.  
Each BiResp Spiromax inhaler contains 120 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 your country.  
 
 
Marketing Authorisation Holder  
 
Teva Pharma B.V.,  
Swensweg 5, 2031GA Haarlem, The Netherlands.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


54 

Manufacturer 
 
Norton (Waterford) Limited T/A Teva Pharmaceuticals Ireland 
Unit 27/35, IDA Industrial Park, Cork Road, Waterford, Ireland 
 
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, Netherlands 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 

Luxembourg/Luxemburg 
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 
 

България 
Actavis EAD 
Teл: +359 2 489 95 85 
 

Magyarország 
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111 
 

Malta 
Teva Pharmaceuticals Ireland 
L-Irlanda 
Tel: +353 51 321 740 
 

Danmark 
Teva Denmark A/S  
Tlf: +45 44 98 55 11 
 
 

Nederland 
Teva Nederland B.V. 
Tel: +31 800 0228 400 
 

Deutschland 
Teva GmbH 
Tel: +49 731 402 08 

Norge 
Teva Norway AS  
Tlf: +47 6677 55 90 

 
Eesti 
UAB Teva Baltics Eesti filiaal 
Tel: +372 661 0801 

 
Österreich 
ratiopharm Arzneimittel Vertriebs GmbH 
Tel: +43 1 97007 0 
 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 880 5000 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 

España 
Laboratorios BIAL, S.A. 
Tel.: +34 915624196 
 

Portugal  
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 
 

France 
Teva Santé 
Tél: +33 1 55 91 7800 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 6524 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

Ísland Slovenská republika 



55 

Vistor hf. 
Simi: +354 535 7000 
 

Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 028 917 981 
 

Suomi/Finland 
Teva Finland Oy 
Puh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 
 

Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 
 

Latvija 
UAB Teva Baltics filiāle Latvijā  
Tel: +371 67 323 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 
 

Lietuva 
UAB Teva Baltics 
Tel: +370 5 266 02 03 
 

Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 
 

 
This leaflet was last revised in month YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 

http://www.ema.europa.eu/


56 

Package leaflet: Information for the patient 
 

BiResp Spiromax 320 micrograms/9 micrograms, inhalation powder 
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 nurse. 
- 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 BiResp Spiromax is and what it is used for 
2. What you need to know before you use BiResp Spiromax 
3. How to use BiResp Spiromax 
4. Possible side effects 
5. How to store BiResp Spiromax 
6. Contents of the pack and other information 
 
 
1. What BiResp Spiromax is and what it is used for 
 
BiResp 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 
more easily.  

• Formoterol fumarate dihydrate belongs to a group of medicines called ‘long-acting β2 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. 

 
BiResp Spiromax is indicated for use in adults 18 years of age and older only.  
BiResp Spiromax is NOT indicated for use in children, 12 years of age and younger or adolescents, 13 
to 17 years of age. 
 
Your doctor has prescribed this medicine to treat asthma or chronic obstructive pulmonary disease (COPD).  
 
Asthma 
When used for asthma, your doctor will prescribe BiResp Spiromax together with a separate ‘reliever 
inhaler’ such as salbutamol. 
 
• Use BiResp 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 BiResp 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. BiResp Spiromax 
can also be used to treat the symptoms of severe COPD in adults.  
 
 



57 

2. What you need to know before you use BiResp Spiromax  
 
Do not use BiResp 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 BiResp Spiromax if 
• 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 BiResp 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 BiResp Spiromax. 
 
Your doctor may consider adding steroid tablets to your usual treatment if you have an illness such as  a 
chest infection or before an operation. 
 
Contact your doctor if you experience blurred vision or other visual disturbances. 
 
Children and adolescents 
This medicine should not be used in children or adolescents under the age of 18 years. 
 
Other medicines and BiResp 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 following medicines: 
• β blockers (such as atenolol or propranolol for high blood pressure or a heart condition), including 

eyedrops (such as timolol for glaucoma). 
• 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 antidepressant nefazodone. 
• Antidepressant medicines such as monoamine oxidase inhibitors and those with similar properties (such 

as the antibiotic furazolidine and the chemotherapy medicine procarbazine).  
• Antipyschotic phenothiazine medicines (such as chlorpromazine and prochlorperazine).  
• Medicines called ‘HIV protease inhibitors’ (such as ritonavir) to treat HIV infection. 



58 

• 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 BiResp 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 
BiResp 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 BiResp Spiromax - do NOT use this medicine 
unless your doctor tells you to.  

• If you get pregnant while using BiResp Spiromax, do NOT stop using BiResp Spiromax but talk to your 
doctor immediately. 

 
Driving and using machines 
 
BiResp Spiromax is not likely to affect your ability to drive or to use tools or machines. 
 
BiResp 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.   

 
3. How to use BiResp Spiromax 

 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
pharmacist, or nurse if you are not sure. 
 

• It is important to use BiResp Spiromax every day, even if you have no asthma or COPD symptoms at 
the time.  

 
• If you are using BiResp Spiromax for asthma, your doctor will want to regularly check your 

symptoms.  
 
Asthma  
 
Use your BiResp Spiromax every day. This helps to prevent asthma symptoms from occurring..  
 
 Recommended dose:  
 
Adults (18 years and older) 
1 inhalation (actuation), twice a day, taken in the morning and in the evening.  
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. 
 

 
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 BiResp 
Spiromax, your doctor may prescribe an alternative inhaler containing the same active substances as your 



59 

BiResp 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 BiResp Spiromax to treat these asthma symptoms.  
 
Chronic Obstructive Pulmonary Disease (COPD) 
 
Recommended dose: 
 
Adults (18 years and older): 
• 1 inhalation twice a day, taken in the morning and in the evening. 
 
Your doctor may also prescribe another bronchodilator medicine for example an anticholinergic (such as 
tiotropium or ipratropium bromide) for your COPD disease. 
 
Preparing your new BiResp Spiromax 
Before using your BiResp 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 inhaler.  

• Write the date you opened the foil pouch on the label of the inhaler. 

• Do not shake your inhaler before use. 
 
How to take an inhalation 
Every time you need to take an inhalation, follow the instructions below. 
 
1.    Hold your inhaler with the semi-transparent wine red mouthpiece cover at the bottom. 

  
 

2. 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. 

 

  



60 

 
3. Breathe out gently (as far as is comfortable). Do not breathe out through your inhaler. 
4.   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.  

 

 

 

 

 

 

 

 

 

 

5.   Remove your inhaler from your mouth. You may notice a taste when you take your inhalation.    
 

6.   Hold your breath for 10 seconds or as long as you comfortably can.  
7. 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. 
 



61 

 
 

• 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. 

 
Note:  
• 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 one inhalation.  

• 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 BiResp Spiromax, you should continue to use 
BiResp Spiromax but go to see your doctor as soon as possible, as you may need additional treatment. 
 
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 treatment immediately. 
 
Once your asthma is well controlled your doctor may consider it appropriate to gradually reduce the dose of 
BiResp Spiromax. 
 
If you use more BiResp 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 advice. 
 
If you use more BiResp Spiromax than you should, contact your doctor, pharmacist or nurse for advice. 
The most common symptoms that may occur after when you use more BiResp Spiromax than you should are 
trembling, headache or a rapid heartbeat.  
 
If you forget to use BiResp 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 usual time. 
 
If you become wheezy or breathless, or develop any other symptoms of an asthma attack, use your ‘reliever 
inhaler’, then seek medical advice.  



62 

 
If you stop using BiResp SpiromaxDo 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. 
 
 
4. 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 BiResp 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 BiResp 
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 BiResp 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. 
• Headache. 
• Pneumonia (infection to the lung) in COPD patients. 

 
Tell your doctor if you have any of the following while taking BiResp 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.  
• Disturbed sleep. 
• Feeling dizzy. 
• Nausea (feeling sick).  
• Fast heartbeat.  
• Bruising of the skin. 
• Muscle cramps 
• Blurred vision.  

 



63 

Rare:  
• Low levels of potassium in your blood.  
• Uneven heartbeat. 
 
Very rare:  
• Depression.  
• 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.  
 
You can also report side effects directly via the national reporting system listed in Appendix V. By reporting 
side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store BiResp 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 25oC.  Keep the mouthpiece cover closed after removal of the foil wrapping. 
• Use within 6 months of removing from the foil wrapping. Use the label on the inhaler to write down 

the  date you open the foil pouch. 
• 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. 
 
 
6. Contents of the pack and other information 
 
What BiResp 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 
fumarate dihydrate.  

 
- The other ingredient is lactose monohydrate (see section 2 under ‘BiResp Spiromax contains lactose’)  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


64 

 
What BiResp Spiromax looks like and contents of the pack 
 
BiResp Spiromax is an inhalation powder.  
Each BiResp 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 your country.  
 
 
Marketing Authorisation Holder  
 
Teva Pharma B.V.,  
Swensweg 5, 2031GA Haarlem, The Netherlands. 
 
Manufacturer: 
 
Norton (Waterford) Limited T/A Teva Pharmaceuticals Ireland 
Unit 27/35, IDA Industrial Park, Cork Road, Waterford, Ireland 
 
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 

Luxembourg/Luxemburg 
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 
 

България 
Actavis EAD 
Teл: +359 2 489 95 85 
 

Magyarország 
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111 
 

Malta 
Teva Pharmaceuticals Ireland 
L-Irlanda 
Tel: +353 51 321 740 
 

Danmark 
Teva Denmark A/S  
Tlf: +45 44 98 55 11 
 

Nederland 
Teva Nederland B.V. 
Tel: +31 800 0228 400 
 

Deutschland 
Teva GmbH 
Tel: +49 731 402 08 
 

Norge 
Teva Norway AS  
Tlf: +47 6677 55 90 

Eesti 
UAB Teva Baltics Eesti filiaal 
Tel: +372 661 0801 

Österreich 
ratiopharm Arzneimittel Vertriebs GmbH 
Tel: +43 1 97007 0 
 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 880 5000 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 



65 

 
España 
Laboratorios BIAL, S.A. 
Tel.: +34 915624196 
 

Portugal  
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 
 

France 
Teva Santé 
Tél: +33 1 55 91 7800 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 6524 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

Ísland 
Vistor hf. 
Simi: +354 535 7000 
 

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 028 917 981 
 

Suomi/Finland 
Teva Finland Oy 
Puh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 
 

Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 
 

Latvija 
UAB Teva Baltics filiāle Latvijā  
Tel: +371 67 323 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 
 

Lietuva 
UAB Teva Baltics 
Tel: +370 5 266 02 03 
 

Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 
 

 
This leaflet was last revised in month YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
 
 
  

http://www.ema.europa.eu/


66 

 

 

 

 

 

 

 

 

 

 

 

 

Annex IV 

Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s) 
  



67 

 

Scientific conclusions  

Taking into account the PRAC Assessment Report on the PSUR(s) for budesonide / formoterol, the 
scientific conclusions of the CHMP are as follows:  

In view of available data on ‘dysphonia’ from clinical trials, the literature and cases reports presented, the 
PRAC considers that a causal relationship between budesonide/formoterol and dysphonia is established. 
The current product information lists ‘hoarseness’ as an undesirable effect in section 4.8 of the SmPC with 
a ‘common’ frequency. the PRAC agreed that ‘hoarseness’ is a term that might be reported in practice, 
however other terms might be reported as well. ‘Hoarseness’ is considered a sub-element of ‘dysphonia’ 
and the two terms cannot be used interchangeably. Therefore, the preferred term (PT) ‘dysphonia’ should 
be included in the product information. However, to indicate that ‘hoarseness’ is the most frequently 
reported lowest level terms (LLT) under the PT ‘dysphonia’ it is proposed to update the product 
information with ‘dysphonia including hoarseness’. The PRAC concluded that the product information of 
products containing budesonide/formoterol should be amended accordingly.  

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s)  

On the basis of the scientific conclusions for budesonide / formoterol the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing budesonide / formoterol is unchanged subject 
to the proposed changes to the product information. 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 
 

 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)