Exubera

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 1 mg inhalation powder pre-dispensed. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each unit dose blister contains 1 mg insulin human.  
 
The exposure of human insulin following administration of three 1 mg blisters is significantly greater 
than that following a single 3 mg blister.  Therefore, the 3 mg blister is not interchangeable with three 
1 mg blisters (see sections 4.2, 4.4 and 5.2). 
 
Produced by recombinant DNA technology in Escherichia coli. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Inhalation powder, pre-dispensed. 
 
White powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
EXUBERA is indicated for the treatment of adult patients with type 2 diabetes mellitus not 
adequately controlled with oral antidiabetic agents and requiring insulin therapy.  
 
EXUBERA is also indicated for the treatment of adult patients with type 1 diabetes mellitus, in 
addition to long or intermediate acting subcutaneous insulin, for whom the potential benefits of 
adding inhaled insulin outweigh the potential safety concerns (see section 4.4).   
 
4.2 Posology and method of administration 
 
EXUBERA (inhaled human insulin) is a fast-acting human insulin for use in type 1 or type 2 diabetes. 
Inhaled human insulin may be used alone or in combination with oral antidiabetic agents and/or long 
or intermediate acting subcutaneously administered insulins to optimise glycaemic control. 
 
EXUBERA is available in 1 mg and 3 mg unit dose blisters which are for administration via the lungs 
by oral inhalation only with the insulin inhaler. 
 
Consecutive inhalation of three 1 mg unit dose blisters causes a significantly higher insulin exposure 
than inhalation of one 3 mg unit dose blister. Therefore three 1 mg unit dose blisters should not be 
substituted for one 3 mg unit dose blister (see sections 2, 4.4 and 5.2). 
 
Inhaled human insulin has a faster onset of activity than subcutaneously administered fast-acting 
human insulin. Due to the rapid onset of activity, inhaled human insulin should be given within 10 
minutes before the start of a meal. 



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The starting and subsequent dosage (dose and timings) should be determined individually by the 
physician and adjusted according to the patient’s individual response and requirements (e.g. diet, 
physical activity and life-style). 
 
Daily doses and timing of administration 
 
There are no fixed rules for insulin dosage. However, a recommended starting daily dose is based on 
the following formula: 
 
Body weight (kg) X 0.15 mg/kg = Total Daily Dose (mg).  The total daily dose should be divided into 
three pre-meal doses. 
 
Approximate guidelines for initial, pre-meal EXUBERA doses, based on patient body weight, are 
indicated in Table 1: 
 

Patient Weight 
Initial Dose per 

Meal 
Approximate 

IU Dose 
Number of 1 mg 
Blisters per Dose 

Number of 3 mg 
Blisters per Dose 

30 to 39.9 kg 1 mg per meal 3 IU 1 - 
40 to 59.9 kg 2 mg per meal 6 IU 2 - 
60 to 79.9 kg 3 mg per meal 8 IU - 1 
80 to 99.9 kg 4 mg per meal 11 IU 1 1 

100 to 119.9 kg 5 mg per meal 14 IU 2 1 
120 to 139.9 kg 6 mg per meal 16 IU - 2 

 
Table 1: Approximate Guidelines for Initial, Pre-Meal EXUBERA Dose (based on patient 
body weight). 
 
A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of subcutaneously injected fast-
acting human insulin. A 3 mg blister of inhaled insulin is approximately equivalent to 8 IU of 
subcutaneously injected fast-acting human insulin. Table 1 above presents the approximate IU dose of 
fast-acting human insulin for initial, pre-meal EXUBERA doses in mg. 
 
Therefore, EXUBERA should be used with caution in patients of low body weight. The use of 
EXUBERA in patients requiring dose titrations of less than 1 mg is not recommended (see section 
4.4). 
 
Dose adjustment may be required based on the meal size and nutrient composition, time of day 
(higher insulin requirements in the morning), pre-meal blood glucose concentration, recent or 
anticipated exercise. 
 
During intercurrent respiratory illness (e.g. bronchitis, upper respiratory tract infections) close 
monitoring of blood glucose concentrations and dose adjustment may be required on an individual 
basis (see section 4.4). 
 
For further details on how to use the insulin inhaler refer to the instructions for use (IFU). 
 
Hepatic and renal impairment 
 
In patients with hepatic or renal impairment insulin requirements may be diminished. 
 
Children and adolescents 
 
Long-term safety of inhaled human insulin has not been established in paediatric patients with 
diabetes and its use is therefore not recommended in patients under 18 years of age (see section 5.2). 



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Elderly 
 
Experience with inhaled insulin in patients � 75 years of age is limited. 
 
Congestive heart failure 
 
Experience with inhaled insulin in patients with congestive heart failure is very limited and its use is 
therefore not recommended in such patients where lung function is significantly compromised. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
Hypoglycaemia. 
 
Patients must not smoke during therapy with EXUBERA and must have stopped smoking at least 6 
months prior to starting EXUBERA therapy.  If a patient starts or resumes smoking, EXUBERA must 
be discontinued immediately due to the increased risk of hypoglycaemia and an alternative treatment 
utilised (see section 5.2). 
 
Poorly controlled, unstable, or severe asthma. 
 
Severe (GOLD stage III or IV) Chronic obstructive pulmonary disease (COPD). 
 
4.4 Special warnings and precautions for use 
 
Patients started on EXUBERA must receive comprehensive instructions in the use of the inhaler (see 
IFU). Patients should inhale the insulin powder from the mouthpiece in one slow and steady 
inhalation. Patients should then hold their breath for 5 seconds and exhale normally. A consistent and 
standard inhalation technique should be employed to ensure both optimal and consistent drug 
delivery. 
 
Patients should avoid exposing the product to high moisture or relative humidity conditions e.g. a 
steamy bathroom, when taking their dose. 
 
If the insulin inhaler is inadvertently exposed to extremely moist conditions during use this usually 
leads to a subsequent decreased insulin dose delivered from the inhaler. In this case, the Insulin 
Release Unit (IRU) must be changed prior to the next inhalation (see section 6.6). 
 
Dosing 
 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision as this may result in a change in dosage. 
 
Consecutive inhalation of three 1 mg unit dose blisters causes a significantly higher insulin exposure 
than inhalation of one 3 mg unit dose blister. Therefore three 1 mg unit dose blisters should not be 
substituted for one 3 mg unit dose blister (see sections 2, 4.2 and 5.2). 
 
If the 3 mg blister is temporarily unavailable, two 1 mg blisters should be substituted and blood 
glucose monitored closely. 
 
A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of subcutaneously injected fast-
acting human insulin. Therefore, EXUBERA should be used with caution in patients of low body 
weight. The use of EXUBERA in patients requiring dose titrations of less than 1 mg is not 
recommended (see section 4.2). 



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Hypoglycaemia 
 
Hypoglycaemia, in general the most frequent undesirable effect of insulin therapy including 
EXUBERA and many oral antidiabetic agents, may occur if the insulin dose is too high in relation to 
the insulin requirement. Severe hypoglycaemic attacks, especially if recurrent, may lead to 
neurological damage. Prolonged or severe hypoglycaemic episodes may be life threatening. 
 
Symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, 
fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in 
concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation. 
Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary 
or permanent impairment of brain function or even death. 
 
Hypoglycaemia can generally be corrected by immediate carbohydrate intake. In order to be able to 
take action immediately, patients should carry glucose with them at all times. 
 
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. 
Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy, may 
experience a change in their usual warning symptoms of hypoglycaemia and should be advised 
accordingly. 
 
Usual warning symptoms may disappear in patients with longstanding diabetes. 
 
A few patients who have experienced hypoglycaemic reactions after transfer from animal source 
insulin to human insulin have reported that early warning symptoms of hypoglycaemia were less 
pronounced or different from those experienced with their previous insulin. 
 
Before travelling between different time zones, the patient should be advised to consult the doctor, 
since this may mean that the patient has to take insulin and meals at different times. 
 
Inadequate dosage or discontinuation of treatment especially in insulin-dependant diabetics, may lead 
to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal. 
 
When used with other antidiabetic agents, the dose of each agent should be carefully adjusted to 
determine the optimal dose required to achieve the desired pharmacological effect. 
 
Insulin requirements may be altered during intercurrent conditions such as illness, emotional 
disturbances, or stress. 
 
Pulmonary Safety 
 
Underlying respiratory disorders 
 
EXUBERA should not be used in patients with lung disease such as asthma and COPD, as there are 
insufficient data to support the safe use in these patients. 
 
The concomitant use of bronchodilators such as salbutamol may increase the absorption of 
EXUBERA and may therefore increase the risk of hypoglycaemia when used to relieve acute 
respiratory symptoms (see section 4.5). 
 
Respiratory 
 
Bronchospasm may rarely occur. Any patients experiencing such a reaction should discontinue 
EXUBERA and seek medical evaluation immediately. Re-administration of EXUBERA requires a 
careful risk evaluation, and may only be done under close medical monitoring with appropriate 
clinical facilities. 



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Decline in pulmonary function 
 
In clinical trials small but consistent treatment group differences in decline of pulmonary function 
(particularly Forced Expiratory Volume in one second (FEV1)) favouring comparator treated subjects 
have been observed. In clinical studies of up to two years duration, there was no accelerated decline 
beyond 3-6 months. These small treatment group differences resolved within 6 weeks upon 
discontinuation after 2 years of treatment (see sections 4.8 and 5.1). 
 
All patients initiated on EXUBERA should have a baseline lung function examination (e.g. 
spirometry to measure FEV1). The efficacy and safety of inhaled human insulin in patients with 
baseline FEV1 < 70% predicted have not been established and the use of inhaled human insulin in this 
population is not recommended. A follow-up lung function measurement is recommended after the 
first 6 months of therapy. If at 6 months a decline of < 15% FEV1 is observed, spirometry should be 
repeated at one year and then annually. If at 6 months a decline of 15-20% or > 500ml from baseline 
lung function is observed, spirometry should be repeated after 3 months. 
 
In patients with a confirmed (i.e. at least two consecutive tests, 3 to 4 weeks apart) FEV1  decline of  
> 20% from baseline, EXUBERA therapy should be discontinued and the patient monitored as 
clinically indicated. There is no experience with the reinstitution of EXUBERA therapy in patients 
whose lung function recovers. 
 
Patients developing dyspnoea while treated with EXUBERA should be examined for pulmonary or 
cardiac causes. Where pulmonary oedema is present, or there is a clinically relevant reduction in 
pulmonary function, EXUBERA should be discontinued and the patient switched to injectable insulin. 
 
Intercurrent Respiratory Illness 
 
EXUBERA has been administered to patients with intercurrent respiratory illness (e.g. bronchitis, 
upper respiratory tract infections) during clinical trials. Increased risk of hypoglycaemia or poor 
glycaemic control has not been observed in these trials. During intercurrent respiratory illness close 
monitoring of blood glucose concentrations and dose adjustment may be required on an individual 
basis (see section 4.2). There is no experience with EXUBERA in patients with pneumonia. 
 
Former Smokers 
 
In clinical trials of Exubera, there have been 6 newly diagnosed cases of primary lung malignancies 
among Exubera-treated patients, and 1 newly diagnosed case among comparator treated patients. 
There has also been 1 post-marketing report of a primary lung malignancy in an Exubera-treated 
patient. In controlled clinical trials of Exubera, the incidence of new primary lung cancer per 100 
patient-years of study drug exposure was 0.130 (5 cases over 3800 patient-years) for Exubera-treated 
patients and 0.03 (1 case over 3900 patient-years) for comparator-treated patients. There were too few 
cases to determine whether the emergence of these events is related to Exubera. All patients who were 
diagnosed with lung cancer had a prior history of cigarette smoking. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of insulin. 
 
Substances that may enhance the blood-glucose lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic agents, angiotensin converting enzyme (ACE) inhibitors, 
monoamino oxidase (MAO) inhibitors, non-selective beta-blocking agents, salicylates and 
sulphonamide antibiotics. 
 
Administration of salbutamol prior to EXUBERA may result in increased insulin absorption (see 
section 5.2).  
 



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Administration of fluticasone prior to EXUBERA does not appear to affect insulin absorption (see 
section 5.2). 
  
Active smoking greatly enhances whereas passive exposure to tobacco smoke in non-smokers 
decreases the rate and extent of absorption of EXUBERA (see sections 4.3 and 5.2). 
 
Substances that may reduce the blood-glucose lowering effect include corticosteroids, danazol, oral 
contraceptives, thyroid hormones, growth hormone, sympathomimetic agents and thiazides. 
Octreotide/lanreotide may both decrease or increase insulin requirements. 
 
Beta-blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify and prolong 
the hypoglycaemic effect of insulin. 
 
Administration of EXUBERA 10 minutes prior to administration of salbutamol did not affect the 
bronchodilatory response to salbutamol in non-diabetic subjects with mild-moderate asthma.   
 
Other drugs that may alter pulmonary absorption or lung permeability have not been studied. Close 
monitoring of blood glucose concentrations and dose titration as appropriate are recommended when 
inhaled human insulin is used in these patients. Caution should be exercised with concomitant use of 
EXUBERA and such drugs. 
 
4.6 Pregnancy and lactation 
 
There is no clinical experience with EXUBERA use in pregnancy. Inhaled insulin frequently induces 
insulin antibodies, the risk of which to the foetus is not known. Therefore, EXUBERA should not be 
used during pregnancy.  When an EXUBERA treated patient becomes pregnant appropriate 
subcutaneous insulin should be substituted for inhaled insulin. 
 
Breast-feeding women may require adjustments in insulin dose and diet. 
 
4.7 Effects on ability to drive and use machines 
 
As with other insulins, the patient's ability to concentrate and react may be impaired as a result of 
hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance 
(e.g. driving a car or operating machinery). 
 
4.8 Undesirable effects 
 
The safety of EXUBERA alone, or in combination with subcutaneous insulin or oral agents has been 
evaluated in clinical studies of more than 2700 patients with type 1 or type 2 diabetes, including more 
than 1975 adults exposed for greater than 6 months and more than 745 adults for greater than 2 years. 
 



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The table below contains adverse reactions seen in controlled clinical studies including more than 
1970 patients exposed to EXUBERA. 
 

Body System Very Common 
(� 1/10) 

Common 
(� 1/100, < 1/10) 

Uncommon 
(� 1/1000, < 1/100) 

Infections and 
Infestations 

  Pharyngitis 

Metabolism and 
Nutritional 
Disorders 

Hypoglycaemia   

Respiratory, 
Thoracic and 
Mediastinal 
Disorders 

Cough Dyspnoea 
Productive Cough 
Throat Irritation 

 Dry Throat  

Epistaxis 
Bronchospasm 

Wheezing 
Dysphonia 

Pharyngolaryngeal 
Pain 

Tonsillar Disorder 
Gastrointestinal 

Disorders 
  Dry Mouth 

General 
Disorders and 
Administration 
Site Conditions 

  Chest Pain 

 
Note: In the overall clinical program, including uncontrolled extension studies, there were two 
reports of pleural effusion in which a treatment-related effect could not be excluded. 

 
Hypoglycaemia 
 
As with other insulins, hypoglycaemia was the most frequently observed undesirable effect in patients 
treated with EXUBERA. 
 
Cough 
 
The cough tended to occur within seconds to minutes after insulin inhalation and was predominantly 
mild in severity. This cough decreased over time. One percent of patients discontinued EXUBERA 
treatment due to cough. 
 
Dyspnoea 
 
The majority (> 95%) of dyspnoea was reported as mild to moderate. In EXUBERA treated subjects 
0.4% discontinued treatment due to dyspnoea.  
 
Chest pain 
 
A range of different chest symptoms were reported as treatment-related adverse reactions and were 
referred to as non-specific chest pain. The majority (> 95%) of these events was reported as mild to 
moderate. One subject in the EXUBERA and one in the comparator group discontinued treatment due 
to chest pain. Importantly, the incidence of all-causality adverse events related to coronary artery 
disease, such as angina pectoris or myocardial infarction was not increased with the use of 
EXUBERA.  
 



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Other reactions 
 
FEV1 decline 
 
Small treatment group differences in decline of FEV1 were observed in the EXUBERA group relative 
to comparator therapy. In clinical studies of up to two years duration, there was no accelerated decline 
beyond 3-6 months. Discontinuation of EXUBERA therapy after 2 years resulted in resolution of 
treatment group differences within 6 weeks (see sections 4.4 and 5.1). 
 
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated type 1 subjects 
and in 5.0% of EXUBERA-treated type 2 subjects. 
 
Insulin antibodies 
 
Insulin antibodies may develop during treatment with all insulins including EXUBERA. In clinical 
trials, insulin antibodies developed more frequently and mean levels of insulin antibodies were higher 
in patients who switched their subcutaneous human insulin to EXUBERA compared to subjects who 
remained on subcutaneous human insulin. Insulin antibody levels were higher in patients with type 1 
diabetes compared to type 2 diabetes and plateaued within 6-12 months of exposure in both groups. 
No clinical significance of these antibodies has been identified. 
 
Hypersensitivity reactions 
 
As with other insulins, generalised allergic reactions may occur very rarely. Such reactions to insulin 
or the excipients may, for example, be associated with generalised skin reactions, angio-oedema, 
bronchospasm, hypotension and shock and may be life-threatening (see section 4.4 Respiratory). 
 
Oedema and refraction abnormalities of the eye  
 
Insulin therapy may cause sodium retention and oedema. Refraction abnormalities of the eye may 
occur upon initiation of insulin therapy. These effects are usually transitory. 
 
4.9 Overdose 
 
Hypoglycaemia may occur as a result of an excess of insulin relative to food intake, energy 
expenditure or both. 
 
Mild episodes of hypoglycaemia usually can be treated with oral carbohydrates. Adjustments in drug 
dosage, meal patterns, or exercise may be needed. 
 
More severe episodes, with coma, seizure, or neurological impairment may be treated with 
intramuscular/subcutaneous glucagon (0.5 to 1 mg) or concentrated intravenous glucose. Glucose 
must also be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes.  
 
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in 
order to prevent relapse. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Medicinal products used in diabetes, ATC code: A10AF01 
 



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Mode of Action 
 
Human insulin lowers blood glucose and promotes anabolic effects as well as decreasing catabolic 
effects, increases the transport of glucose into cells as well as the formation of glycogen in the 
muscles and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and 
gluconeogenesis, increases lipogenesis in the liver and adipose tissue and inhibits lipolysis. It also 
promotes the uptake of amino acids into cells and promotes protein synthesis and enhances the uptake 
of potassium into cells. 
 
Inhaled human insulin, like fast-acting insulin analogues, has a more rapid onset of glucose lowering 
activity compared to subcutaneously administered soluble human insulin. Inhaled human insulin has a 
duration of glucose lowering activity comparable to subcutaneously administered fast-acting human 
insulin and longer than fast-acting insulin analogues (see Figure 1). 
 
 

 
Figure 1. Mean Glucose Infusion Rate (GIR) Normalised to GIRmax for Each Subject Treatment 
Versus Time in Healthy Volunteers. 
 
When human insulin is inhaled, the onset of glucose lowering activity is within 10-20 minutes, the 
maximum effect is exerted approximately 2 hours after inhalation. The duration of action lasts 
approximately 6 hours. 
 
In subjects with type 1 or type 2 diabetes, inhaled human insulin has a faster onset of glucose 
lowering effect in the early hours after dosing when compared with subcutaneously administered fast-
acting human insulin. 
 
The intra-subject variability of glucose lowering activity of inhaled human insulin was generally 
comparable to that of subcutaneously administered fast-acting human insulin in subjects with type 1 
and 2 diabetes mellitus. 
 
Use of inhaled human insulin is associated with an increase in frequency, and levels of insulin 
antibodies. In a prospective exploratory 6 month study in subjects with type 1 diabetes, alterations in 
the glucose pharmacodynamics with inhaled human insulin were not observed. 
 
Information on Clinical Trials 
 
Controlled clinical trials in type 1 or type 2 diabetes have shown that EXUBERA achieves and 
maintains effective glycaemic control comparable to subcutaneously administered fast-acting human 
insulin.  
 

   

M
ea

n 
G

IR
 (%

 o
f M

ax
im

um
)   

Time (min)   
(

SC Lispro (18 U)   
Exubera (6mg)  

)
Fast-acting 
Human Insulin 
(18 U) 

  



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Type 1 Diabetes  
 
In clinical trials in type 1 diabetes, patients using a regimen of EXUBERA in combination with long- 
or intermediate-acting insulin had similar reductions in HbA1c compared with patients taking 
subcutaneous insulin alone. The percentage of patients who achieved a goal of HbA1c < 7.0% was 
comparable between the treatment groups. 
 
Fasting plasma glucose levels were significantly lower in patients treated with regimens including 
EXUBERA compared with those treated with subcutaneously administered fast-acting human insulin 
only regimens.  
 
Type 2 Diabetes 
 
Patients in a clinical trial for type 2 diabetes, who used a regimen of EXUBERA in combination with 
long- or intermediate-acting insulin, had similar changes in HbA1c compared with patients treated 
with subcutaneous insulin alone.  
Fasting plasma glucose levels were significantly lower in patients treated with EXUBERA regimens 
compared with those treated with subcutaneous insulin.  
 
In clinical trials involving patients with type 2 diabetes not sufficiently controlled with oral agents 
alone, patients using a regimen of EXUBERA alone or in combination with oral agents, had greater 
improvements in HbA1c compared with patients treated with oral agents alone. In most of these 
studies the percentages of patients achieving HbA1c < 7.0% were higher for patients using a regimen 
including EXUBERA compared to patients on oral agents alone. Fasting plasma glucose was similar 
to or lower in patients using a regimen including EXUBERA compared to patients treated with oral 
agents alone. In patients with type 2 diabetes sufficiently controlled with oral agents the glycaemic 
control was not further improved by inhaled insulin. 
FEV1 decline 
 
Randomised, open label parallel group studies were conducted to examine FEV1 changes following 
initiation of EXUBERA therapy in type 1 and 2 subjects. Both EXUBERA and comparator treated 
subjects experienced declines in lung function over time during these trials (Figures 2 and 3). Small 
treatment group differences (favouring comparator) in change from baseline of 0.034L in type 1 and 
0.039L in type 2 occurred after 2 years of therapy. 
 
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated and 1.0% of 
comparator-treated type 1 subjects and in 5.0% of EXUBERA-treated and 3.4% of comparator-treated 
type 2 subjects. 



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 Figure 2. Observed Change from Baseline in FEV1 (L) in patients with type 1 diabetes mellitus. 
 

Figure 3. Observed Change from Baseline in FEV1 (L) in patients with type 2 diabetes mellitus. 
 
In Phase 2/3 trials, 9 out of 2498 subjects treated with EXUBERA were discontinued from trials due 
to a decline in pulmonary function whose end of study FEV1 showed a decline of  ≥ 15% from 
baseline. These subjects experienced an average decrease in FEV1 of 21% (range 16%-33%) from 
baseline and were treated with EXUBERA for an average of 23 months. 6 of these discontinued 
subjects underwent follow-up pulmonary function testing. Of these patients, 5 exhibited a significant 
improvement in FEV1 following discontinuation of therapy and one subject did not decrease further 
from the end of study value. No further information is available for the remaining 3 subjects who 
discontinued. 
 

-0 .5
-0 .45

-0 .4

-0 .35

-0 .3
-0 .25

-0 .2

-0 .15
-0 .1

-0 .05
0

0 .05

0 .1

0 .15
0 .2

0 .25

0 .3
IN H
C o mp arato r

C
ha

ng
e 

fr
om

 B
as

el
in

e 
in

 F
E

V
1

(L
) 

( M
ea

n 
+/

-
S

D
)

N=Number of Subjects at Baseline, week 12, week 24, week 36 , week 48, week 60 , week 72 , 
week 84 , week 96, LOCF.
INH N= 236, 231, 233, 233, 235, 235, 226, 217, 208, 236. Comparator N= 253, 238, 252, 248, 
252, 249, 230, 224, 216, 253.

Baseline 12 24 36 48 60 72 84 96 LOCF

Visit (weeks)

C
ha

ng
e 

fr
om

 B
as

el
in

e 
in

 F
E

V
1

(L
) 

( M
ea

n 
+/

-
S

D
)

-0.5
-0.45

-0.4
-0.35

-0.3
-0.25

-0.2
-0.15

-0.1
-0.05

0
0.05

0.1
0.15

0.2
0.25

0.3

Baseline 24 36 52 65 78 91 104 +6 +12

Visit (weeks)

INH
Comparator
INH Washout

N=Number of Subjects at Baseline, week 52, week 104, week +6, week +12.
INH and INH washout N=158, 155, 143, 139, 123. Comparator N=145, 143, 125, 129, 120.

Comparative Phase Washout Phase



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FEV1 reversibility 
 
In type 1 subjects, resolution of small treatment group differences (0.010L favouring comparator) 
occurred within 2 weeks of EXUBERA cessation following 12 weeks of therapy. In type 2 subjects, 
resolution of small treatment group differences (0.039L favouring comparator) occurred within 6 
weeks of EXUBERA cessation following 2 years of therapy (Figure 3). In a smaller group (n=36) of 
mixed type 1 and 2 subjects treated with EXUBERA for > 36 months, cessation of therapy resulted in 
a mean FEV1 increase of 0.036L over the subsequent 6 months. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Inhaled human insulin is delivered by the pulmonary route. Inhaled human insulin is absorbed as 
rapidly as fast-acting insulin analogues and more rapidly than subcutaneously administered fast-acting 
human insulin in healthy subjects and in subjects with type 1 or type 2 diabetes (see Figure 4). 
 
 

Figure 4: Mean changes in serum free insulin concentrations (µU/mL) after inhalation of 4mg of 
human insulin or subcutaneous injection of 12 IU fast-acting human insulin in obese subjects with 
type 2 diabetes. 
 
The time to peak insulin concentration (Tmax) is generally half of that for subcutaneously administered 
fast-acting human insulin. Peak insulin concentration is reached generally by 45 minutes for inhaled 
human insulin. Intrasubject variability of time to peak insulin concentrations was less for inhaled 
human insulin than for subcutaneous fast-acting human insulin in subjects with type 1 or 2 diabetes. 
 
In subjects with type 1 diabetes mellitus, inhaled human insulin had a comparable intrasubject 
variability of AUC to subcutaneously administered fast-acting human insulin. For Cmax, the 
intrasubject variability of inhaled insulin is greater than that of subcutaneously administered fast-
acting human insulin. In obese subjects with type 2 diabetes, intrasubject variability was comparable 
to or less than that of subcutaneously administered fast-acting human insulin for Cmax and AUC. 
 
The relative bioavailability of EXUBERA compared to subcutaneous fast-acting human insulin is 
approximately 10%. Unlike subcutaneous insulin preparations, the bioavailability of EXUBERA is 
not influenced by Body Mass Index. 
 
In a study in healthy subjects, systemic exposure (AUC and Cmax) of inhaled human insulin 

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Subcutaneo us Insulin

EXUBERA (4mg) 

Fast-acting Human Insulin (12 IU) 



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increased in an approximately dose proportional fashion from 1 mg to 6 mg when a maximum of two 
blisters from either strength or their combination was administered. In a study where the dosage form 
of three 1 mg blisters was compared with one 3 mg blister, Cmax and AUC of inhaling three 1 mg 
blisters were approximately 30% and 40% greater, respectively, than that of inhaling from one 3 mg 
blister, indicating that three 1 mg blisters are not interchangeable with one 3 mg blister (see sections 
2, 4.2 and 4.4).  
 
An approximately 40% higher bioavailability of three 1 mg unit dose blisters compared to one 3 mg 
unit dose blister was observed in healthy subjects. An explanation for the differences in 
bioavailability appears to be the different energy to mass ratio between the 1 and 3 mg unit blisters 
since with less powder in the blister the inhaler is more efficient in breaking up or de-agglomerating 
the powder leading to a larger proportion of smaller aerodynamic particle sizes for the 1 mg blister 
(see sections 2 and 4.4). 
 
Distribution 
 
Following oral inhalation of a single dose of human insulin approximately 30% of the total blister 
content remains in the blister or device, 20% is deposited in the oropharynx, 10% in the conducting 
airways and 40% reaches the deep lung.   
 
Animal studies did not show that inhaled human insulin accumulates in the lung. 
 
Special Populations 
 
Smoking 
 
Smoking greatly increases the rate and extent of absorption of inhaled human insulin (Cmax about 3 to 
5 times and AUC about 2 to 3 times higher) and therefore could increase the risk of hypoglycaemia 
(see sections 4.3 and 4.5).  
 
When EXUBERA was administered to healthy volunteers following 2-hours of passive exposure to 
cigarette smoke in a controlled experimental setting, insulin AUC and Cmax were reduced by 
approximately 17 and 30%, respectively (see section 4.5). 
 
Respiratory Diseases (Underlying Lung Disease) 
 
In non-diabetic subjects with mild to moderate asthma, AUC and Cmax for inhaled human insulin in 
the absence of treatment with a bronchodilator was slightly less than in subjects without asthma. 
 
In non-diabetic subjects with COPD, the absorption of inhaled human insulin appeared greater 
compared with that in subjects without COPD (see section 4.4).   
 
Administration of salbutamol 30 minutes prior to EXUBERA in non-diabetic subjects with mild-
moderate asthma resulted in an increase in insulin AUC and Cmax of between 25 and 51% compared to 
when EXUBERA was administered alone (see sections 4.2 and 4.5).  
 
Administration of fluticasone 30 minutes prior to EXUBERA did not affect the pharmacokinetics of 
EXUBERA in non-diabetic subjects with mild-moderate asthma (see section 4.5).  
 
Renal impairment 
 
The effect of renal impairment on the absorption of inhaled human insulin has not been studied (see 
section 4.2). 
 



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Hepatic impairment 
 
The effect of hepatic impairment on the absorption of inhaled human insulin has not been studied (see 
section 4.2). 
 
Gender 
 
In subjects with diabetes and in subjects without diabetes, no apparent differences in absorption of 
inhaled human insulin were observed between men and women. 
 
Children and adolescents 
 
In children (6-11 years) and adolescents (12-17 years) with type 1 diabetes, inhaled human insulin 
was absorbed more rapidly than fast-acting human insulin. Bioavailability of inhaled human insulin 
relative to subcutaneously administered fast-acting human insulin was comparable to that of adult 
subjects with type 1 diabetes (see section 4.2). 
 
Elderly 
 
In older subjects with type 2 diabetes, inhaled human insulin was absorbed more rapidly than 
subcutaneously administered fast-acting human insulin.  Bioavailability of inhaled human insulin 
relative to subcutaneously administered fast-acting human insulin was comparable to those in younger 
adult subjects with type 2 diabetes. 
 
5.3 Preclinical safety data 
 
Inhalation toxicity studies in rats and monkeys for up to 6 months gave no evidence for a special risk 
to the respiratory tract due to insulin inhalation powder. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Glycine 
Sodium Citrate (as dihydrate) 
Sodium Hydroxide 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
 
After first opening the foil overwrap: 3 months. 
 
6.4 Special precautions for storage 
 
Store below 30oC. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25oC.  
 
Do not refrigerate or freeze the unit dose blisters. 



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The inhaler and its components should be stored and used in a dry place. 
 
Do not refrigerate or freeze the insulin inhaler. 
 
6.5 Nature and contents of container 
 
One blister card contains 6 perforated unit dose blisters (PVC/Aluminium). Five blister cards are in a 
clear plastic (PET) thermoformed tray with a desiccant and covered with a clear plastic (PET) lid. The 
tray is sealed in a foil laminate pouch with a desiccant. 
 
Packaging sizes supplied: 
 
• Cardboard box containing 30 x 1 PVC/Aluminium perforated unit dose blisters (1 pouch)  
 
• Cardboard box containing 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches)  
 
• Cardboard box containing 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches) 
 
• Cardboard box containing 180 x 1 PVC/Aluminium perforated unit dose blisters (6 pouches)  
 
• Cardboard box containing 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches)  
 
• Cardboard box containing 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches) and 

2 spare Insulin Release Units (IRU) 
 
• Cardboard box containing 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches) 

and 6 spare Insulin Release Units (IRU) 
 
• A kit containing 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches), 1 insulin 

inhaler, 1 spare chamber and 6 spare Insulin Release Units (IRU) 
 
Additional insulin inhaler, insulin release units and chamber packages are available. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
EXUBERA unit dose blisters must only be used with the insulin inhaler.  
 
The insulin inhaler should be replaced annually. 
 
The Insulin Release Unit (IRU) should be replaced once every 2 weeks. 
 
If the insulin inhaler is inadvertently exposed to extremely moist conditions during use this usually 
leads to a subsequent decreased insulin dose delivered from the inhaler. In this case, the Insulin 
Release Unit (IRU) must be changed prior to the next inhalation (see section 4.4). 
 



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7. MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
Ramsgate Road, Sandwich,  
Kent, CT13, 9NJ 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/327/001 
EU/1/05/327/002 
EU/1/05/327/003 
EU/1/05/327/004 
EU/1/05/327/005 
EU/1/05/327/006 
EU/1/05/327/007 
EU/1/05/327/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
24/01/2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 3 mg inhalation powder pre-dispensed. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each unit dose blister contains 3 mg insulin human. 
 
The exposure of human insulin following administration of three 1 mg blisters is significantly greater 
than that following a single 3 mg blister.  Therefore, the 3 mg blister is not interchangeable with three 
1 mg blisters (see sections 4.2, 4.4 and 5.2). 
 
Produced by recombinant DNA technology in Escherichia coli. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Inhalation powder, pre-dispensed. 
 
White powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
EXUBERA is indicated for the treatment of adult patients with type 2 diabetes mellitus not 
adequately controlled with oral antidiabetic agents and requiring insulin therapy.  
 
EXUBERA is also indicated for the treatment of adult patients with type 1 diabetes mellitus, in 
addition to long or intermediate acting subcutaneous insulin, for whom the potential benefits of 
adding inhaled insulin outweigh the potential safety concerns (see section 4.4). 
 
4.2 Posology and method of administration 
 
EXUBERA (inhaled human insulin) is a fast-acting human insulin for use in type 1 or type 2 diabetes. 
Inhaled human insulin may be used alone or in combination with oral antidiabetic agents and/or long 
or intermediate acting subcutaneously administered insulins to optimise glycaemic control. 
 
EXUBERA is available in 1 mg and 3 mg unit dose blisters which are for administration via the lungs 
by oral inhalation only with the insulin inhaler. 
 
Consecutive inhalation of three 1 mg unit dose blisters causes a significantly higher insulin exposure 
than inhalation of one 3 mg unit dose blister. Therefore three 1 mg unit dose blisters should not be 
substituted for one 3 mg unit dose blister (see sections 2, 4.4 and 5.2). 
 
Inhaled human insulin has a faster onset of activity than subcutaneously administered fast-acting 
human insulin. Due to the rapid onset of activity, inhaled human insulin should be given within 10 
minutes before the start of a meal. 
 
The starting and subsequent dosage (dose and timings) should be determined individually by the 
physician and adjusted according to the patient’s individual response and requirements (e.g. diet, 
physical activity and life-style). 



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Daily doses and timing of administration 
 
There are no fixed rules for insulin dosage. However, a recommended starting daily dose is based on 
the following formula: 
 
Body weight (kg) X 0.15 mg/kg = Total Daily Dose (mg).  The total daily dose should be divided into 
three pre-meal doses. 
 
Approximate guidelines for initial, pre-meal EXUBERA doses, based on patient body weight, are 
indicated in Table 1: 
 

Patient Weight 
Initial Dose per 

Meal 
Approximate 

IU Dose 
Number of 1 mg 
Blisters per Dose 

Number of 3 mg 
Blisters per Dose 

30 to 39.9 kg 1 mg per meal 3 IU 1 - 
40 to 59.9 kg 2 mg per meal 6 IU 2 - 
60 to 79.9 kg 3 mg per meal 8 IU - 1 
80 to 99.9 kg 4 mg per meal 11 IU 1 1 

100 to 119.9 kg 5 mg per meal 14 IU 2 1 
120 to 139.9 kg 6 mg per meal 16 IU - 2 

 
Table 1: Approximate Guidelines for Initial, Pre-Meal EXUBERA Dose (based on patient 
body weight). 
 
A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of subcutaneously injected fast-
acting human insulin. A 3 mg blister of inhaled insulin is approximately equivalent to 8 IU of 
subcutaneously injected fast-acting human insulin. Table 1 above presents the approximate IU dose of 
fast-acting human insulin for initial, pre-meal EXUBERA doses in mg. 
 
Therefore, EXUBERA should be used with caution in patients of low body weight. The use of 
EXUBERA in patients requiring dose titrations of less than 1 mg is not recommended (see section 
4.4). 
 
Dose adjustment may be required based on the meal size and nutrient composition, time of day 
(higher insulin requirements in the morning), pre-meal blood glucose concentration, recent or 
anticipated exercise. 
 
During intercurrent respiratory illness (e.g. bronchitis, upper respiratory tract infections) close 
monitoring of blood glucose concentrations and dose adjustment may be required on an individual 
basis (see section 4.4). 
 
For further details on how to use the insulin inhaler refer to the instructions for use (IFU). 
 
Hepatic and renal impairment 
 
In patients with hepatic or renal impairment insulin requirements may be diminished. 
 
Children and adolescents 
 
Long-term safety of inhaled human insulin has not been established in paediatric patients with 
diabetes and its use is therefore not recommended in patients under 18 years of age (see section 5.2). 
 
Elderly 
 
Experience with inhaled insulin in patients � 75 years of age is limited. 



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Congestive heart failure 
 
Experience with inhaled insulin in patients with congestive heart failure is very limited and its use is 
therefore not recommended in such patients where lung function is significantly compromised. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients (see section 6.1). 
 
Hypoglycaemia. 
 
Patients must not smoke during therapy with EXUBERA and must have stopped smoking at least 6 
months prior to starting EXUBERA therapy.  If a patient starts or resumes smoking, EXUBERA must 
be discontinued immediately due to the increased risk of hypoglycaemia and an alternative treatment 
utilised (see section 5.2). 
 
Poorly controlled, unstable, or severe asthma. 
 
Severe (GOLD stage III or IV) Chronic obstructive pulmonary disease (COPD). 
 
4.4 Special warnings and precautions for use 
 
Patients started on EXUBERA must receive comprehensive instructions in the use of the inhaler (see 
IFU). Patients should inhale the insulin powder from the mouthpiece in one slow and steady 
inhalation. Patients should then hold their breath for 5 seconds and exhale normally. A consistent and 
standard inhalation technique should be employed to ensure both optimal and consistent drug 
delivery. 
 
Patients should avoid exposing the product to high moisture or relative humidity conditions e.g. a 
steamy bathroom, when taking their dose. 
 
If the insulin inhaler is inadvertently exposed to extremely moist conditions during use this usually 
leads to a subsequent decreased the insulin dose delivered from the inhaler. In this case, the Insulin 
Release Unit (IRU) must be changed prior to the next inhalation (see section 6.6). 
 
Dosing 
 
Transferring a patient to another type or brand of insulin should be done under strict medical 
supervision as this may result in a change in dosage. 
 
Consecutive inhalation of three 1 mg unit dose blisters causes a significantly higher insulin exposure 
than inhalation of one 3 mg unit dose blister. Therefore three 1 mg unit dose blisters should not be 
substituted for one 3 mg unit dose blister (see sections 2, 4.2 and 5.2). 
 
If the 3 mg blister is temporarily unavailable, two 1 mg blisters should be substituted and blood 
glucose monitored closely. 
 
A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of subcutaneously injected fast-
acting human insulin. Therefore, EXUBERA should be used with caution in patients of low body 
weight. The use of EXUBERA in patients requiring dose titrations of less than 1 mg is not 
recommended (see section 4.2). 
 
Hypoglycaemia 
 
Hypoglycaemia, in general the most frequent undesirable effect of insulin therapy including 
EXUBERA and many oral antidiabetic agents, may occur if the insulin dose is too high in relation to 



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the insulin requirement. Severe hypoglycaemic attacks, especially if recurrent, may lead to 
neurological damage. Prolonged or severe hypoglycaemic episodes may be life threatening. 
 
Symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, 
fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in 
concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation. 
Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary 
or permanent impairment of brain function or even death. 
 
Hypoglycaemia can generally be corrected by immediate carbohydrate intake. In order to be able to 
take action immediately, patients should carry glucose with them at all times. 
 
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. 
Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy, may 
experience a change in their usual warning symptoms of hypoglycaemia and should be advised 
accordingly. 
 
Usual warning symptoms may disappear in patients with longstanding diabetes. 
 
A few patients who have experienced hypoglycaemic reactions after transfer from animal source 
insulin to human insulin have reported that early warning symptoms of hypoglycaemia were less 
pronounced or different from those experienced with their previous insulin. 
 
Before travelling between different time zones, the patient should be advised to consult the doctor, 
since this may mean that the patient has to take insulin and meals at different times. 
 
Inadequate dosage or discontinuation of treatment especially in insulin-dependant diabetics, may lead 
to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal. 
 
When used with other antidiabetic agents, the dose of each agent should be carefully adjusted to 
determine the optimal dose required to achieve the desired pharmacological effect. 
 
Insulin requirements may be altered during intercurrent conditions such as illness, emotional 
disturbances, or stress. 
 
Pulmonary Safety 
  
Underlying respiratory disorders 
 
EXUBERA should not be used in patients with lung disease such as asthma and COPD, as there are 
insufficient data to support the safe use in these patients. 
 
The concomitant use of bronchodilators such as salbutamol may increase the absorption of 
EXUBERA and may therefore increase the risk of hypoglycaemia when used to relieve acute 
respiratory symptoms (see section 4.5). 
 
Respiratory 
 
Bronchospasm may rarely occur. Any patients experiencing such a reaction should discontinue 
EXUBERA and seek medical evaluation immediately. Re-administration of EXUBERA requires a 
careful risk evaluation, and may only be done under close medical monitoring with appropriate 
clinical facilities. 
 
 
 



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Decline in pulmonary function 
 
In clinical trials small but consistent treatment group differences in decline of pulmonary function 
(particularly Forced Expiratory Volume in one second (FEV1)) favouring comparator treated subjects 
have been observed. In clinical studies of up to two years duration, there was no accelerated decline 
beyond 3-6 months. These small treatment group differences resolved within 6 weeks upon 
discontinuation after 2 years of treatment (see sections 4.8 and 5.1). 
 
All patients initiated on EXUBERA should have a baseline lung function examination (e.g. 
spirometry to measure FEV1). The efficacy and safety of inhaled human insulin in patients with 
baseline FEV1 < 70% predicted have not been established and the use of inhaled human insulin in this 
population is not recommended A follow-up lung function measurement is recommended after the 
first 6 months of therapy. If at 6 months a decline of < 15% FEV1 is observed, spirometry should be 
repeated at one year and then annually. If at 6 months a decline of 15-20% or > 500ml from baseline 
lung function is observed, spirometry should be repeated after 3 months. 
 
In patients with a confirmed (i.e. at least two consecutive tests, 3 to 4 weeks apart) FEV1  decline of  
> 20% from baseline, EXUBERA therapy should be discontinued and the patient monitored as 
clinically indicated. There is no experience with the reinstitution of EXUBERA therapy in patients 
whose lung function recovers. 
 
Patients developing dyspnoea while treated with EXUBERA should be examined for pulmonary or 
cardiac causes. Where pulmonary oedema is present, or there is a clinically relevant reduction in 
pulmonary function, EXUBERA should be discontinued and the patient switched to injectable insulin. 
 
Intercurrent Respiratory Illness 
 
EXUBERA has been administered to patients with intercurrent respiratory illness (e.g. bronchitis, 
upper respiratory tract infections) during clinical trials. Increased risk of hypoglycaemia or poor 
glycaemic control has not been observed in these trials. During intercurrent respiratory illness close 
monitoring of blood glucose concentrations and dose adjustment may be required on an individual 
basis (see section 4.2). There is no experience with EXUBERA in patients with pneumonia. 
 
Former Smokers 
 
In clinical trials of Exubera, there have been 6 newly diagnosed cases of primary lung malignancies 
among Exubera-treated patients, and 1 newly diagnosed case among comparator treated patients. 
There has also been 1 post-marketing report of a primary lung malignancy in an Exubera-treated 
patient. In controlled clinical trials of Exubera, the incidence of new primary lung cancer per 100 
patient-years of study drug exposure was 0.130 (5 cases over 3800 patient-years) for Exubera-treated 
patients and 0.03 (1 case over 3900 patient-years) for comparator-treated patients. There were too few 
cases to determine whether the emergence of these events is related to Exubera. All patients who were 
diagnosed with lung cancer had a prior history of cigarette smoking. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
A number of substances affect glucose metabolism and may require dose adjustment of insulin. 
 
Substances that may enhance the blood-glucose lowering effect and increase susceptibility to 
hypoglycaemia include oral antidiabetic agents, angiotensin converting enzyme (ACE) inhibitors, 
monoamino oxidase (MAO) inhibitors, non-selective beta-blocking agents, salicylates and 
sulphonamide antibiotics. 
 
Administration of salbutamol prior to EXUBERA may result in increased insulin absorption (see 
section 5.2).  
 



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Administration of fluticasone prior to EXUBERA does not appear to affect insulin absorption (see 
section 5.2).   
 
Active smoking greatly enhances whereas passive exposure to tobacco smoke in non-smokers 
decreases the rate and extent of absorption of EXUBERA (see sections 4.3 and 5.2). 
 
Substances that may reduce the blood-glucose lowering effect include corticosteroids, danazol, oral 
contraceptives, thyroid hormones, growth hormone, sympathomimetic agents and thiazides. 
Octreotide/lanreotide may both decrease or increase insulin requirements. 
 
Beta-blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify and prolong 
the hypoglycaemic effect of insulin. 
 
Administration of EXUBERA 10 minutes prior to administration of salbutamol did not affect the 
bronchodilatory response to salbutamol in non-diabetic subjects with mild-moderate asthma.  
 
Other drugs that may alter pulmonary absorption or lung permeability have not been studied. Close 
monitoring of blood glucose concentrations and dose titration as appropriate are recommended when 
inhaled human insulin is used in these patients. Caution should be exercised with concomitant use of 
EXUBERA and such drugs. 
 
4.6 Pregnancy and lactation 
 
There is no clinical experience with EXUBERA use in pregnancy. Inhaled insulin frequently induces 
insulin antibodies, the risk of which to the foetus is not known. Therefore, EXUBERA should not be 
used during pregnancy.  When an EXUBERA treated patient becomes pregnant appropriate 
subcutaneous insulin should be substituted for inhaled insulin. 
 
Breast-feeding women may require adjustments in insulin dose and diet. 
 
4.7 Effects on ability to drive and use machines 
 
As with other insulins, the patient's ability to concentrate and react may be impaired as a result of 
hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance 
(e.g. driving a car or operating machinery). 
 
4.8    Undesirable effects 
 
The safety of EXUBERA alone, or in combination with subcutaneous insulin or oral agents has been 
evaluated in clinical studies of more than 2700 patients with type 1 or type 2 diabetes, including more 
than 1975 adults exposed for greater than 6 months and more than 745 adults for greater than 2 years. 
 



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The table below contains adverse reactions seen in controlled clinical studies including more than 
1970 patients exposed to EXUBERA. 
 

Body System Very Common 
(� 1/10) 

Common 
(� 1/100, < 1/10) 

Uncommon 
(� 1/1000, < 1/100) 

Infections and 
Infestations 

  Pharyngitis 

Metabolism and 
Nutritional 
Disorders 

Hypoglycaemia   

Respiratory, 
Thoracic and 
Mediastinal 
Disorders 

Cough Dyspnoea 
Productive Cough 
Throat Irritation 

 Dry Throat  

Epistaxis 
Bronchospasm 

Wheezing 
Dysphonia 

Pharyngolaryngeal Pain 
Tonsillar Disorder 

Gastrointestinal 
Disorders 

  Dry Mouth 

General 
Disorders and 
Administration 
Site Conditions 

  Chest Pain 

 
Note: In the overall clinical program, including uncontrolled extension studies, there were two 
reports of pleural effusion in which a treatment-related effect could not be excluded. 
 

Hypoglycaemia 
 
As with other insulins, hypoglycaemia was the most frequently observed undesirable effect in patients 
treated with EXUBERA. 
 
Cough 
 
The cough tended to occur within seconds to minutes after insulin inhalation and was predominantly 
mild in severity. This cough decreased over time. One percent of patients discontinued EXUBERA 
treatment due to cough. 
 
Dyspnoea 
 
The majority (> 95%) of dyspnoea was reported as mild to moderate. In EXUBERA treated subjects 
0.4% discontinued treatment due to dyspnoea.  
 
Chest pain 
 
A range of different chest symptoms were reported as treatment-related adverse reactions and were 
referred to as non-specific chest pain.. The majority (> 95%) of these events was reported as mild to 
moderate. One subject in the EXUBERA and one in the comparator group discontinued treatment due 
to chest pain. Importantly, the incidence of all-causality adverse events related to coronary artery 
disease, such as angina pectoris or myocardial infarction was not increased with the use of 
EXUBERA.  
 



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Other reactions 
 
FEV1 decline 
 
Small treatment group differences in decline of FEV1 were observed in the EXUBERA group relative 
to comparator therapy. In clinical studies of up to two years duration, there was no accelerated decline 
beyond 3-6 months. Discontinuation of EXUBERA therapy after 2 years resulted in resolution of 
treatment group differences within 6 weeks (see sections 4.4 and 5.1). 
 
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated type 1 subjects 
and in 5.0% of EXUBERA-treated type 2 subjects. 
 
Insulin antibodies 
 
Insulin antibodies may develop during treatment with all insulins including EXUBERA. In clinical 
trials, insulin antibodies developed more frequently and mean levels of insulin antibodies were higher 
in patients who switched their subcutaneous human insulin to EXUBERA compared to subjects who 
remained on subcutaneous human insulin. Insulin antibody levels were higher in patients with type 1 
diabetes compared to type 2 diabetes and plateaued within 6-12 months of exposure in both groups. 
No clinical significance of these antibodies has been identified. 
 
Hypersensitivity reactions 
 
As with other insulins, generalised allergic reactions may occur very rarely. Such reactions to insulin 
or the excipients may, for example, be associated with generalised skin reactions, angio-oedema, 
bronchospasm, hypotension and shock and may be life-threatening (see section 4.4 Respiratory). 
 
Oedema and refraction abnormalities of the eye  
 
Insulin therapy may cause sodium retention and oedema. Refraction abnormalities of the eye may 
occur upon initiation of insulin therapy. These effects are usually transitory. 
 
4.9 Overdose 
 
Hypoglycaemia may occur as a result of an excess of insulin relative to food intake, energy 
expenditure or both. 
 
Mild episodes of hypoglycaemia usually can be treated with oral carbohydrates. Adjustments in drug 
dosage, meal patterns, or exercise may be needed. 
 
More severe episodes, with coma, seizure, or neurological impairment may be treated with 
intramuscular/subcutaneous glucagon (0.5 to 1 mg) or concentrated intravenous glucose. Glucose 
must also be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes.  
 
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in 
order to prevent relapse. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Medicinal products used in diabetes, ATC code: A10AF01 
 



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Mode of Action 
 
Human insulin lowers blood glucose and promotes anabolic effects as well as decreasing catabolic 
effects, increases the transport of glucose into cells as well as the formation of glycogen in the 
muscles and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and 
gluconeogenesis, increases lipogenesis in the liver and adipose tissue and inhibits lipolysis. It also 
promotes the uptake of amino acids into cells and promotes protein synthesis and enhances the uptake 
of potassium into cells. 
 
Inhaled human insulin, like fast-acting insulin analogues, has a more rapid onset of glucose lowering 
activity compared to subcutaneously administered soluble human insulin. Inhaled human insulin has a 
duration of glucose lowering activity comparable to subcutaneously administered fast-acting human 
insulin and longer than fast-acting insulin analogues (see Figure 1). 
 

Figure 1. Mean Glucose Infusion Rate (GIR) Normalised to GIRmax for Each Subject Treatment 
Versus Time in Healthy Volunteers. 
 
When human insulin is inhaled, the onset of glucose lowering activity is within 10-20 minutes, the 
maximum effect is exerted approximately 2 hours after inhalation. The duration of action lasts 
approximately 6 hours. 
 
In subjects with type 1 or type 2 diabetes, inhaled human insulin has a faster onset of glucose 
lowering effect in the early hours after dosing when compared with subcutaneously administered fast-
acting human insulin. 
 
The intra-subject variability of glucose lowering activity of inhaled human insulin was generally 
comparable to that of subcutaneously administered fast-acting human insulin in subjects with type 1 
and 2 diabetes mellitus. 
 
Use of inhaled human insulin is associated with an increase in frequency, and levels of insulin 
antibodies. In a prospective exploratory 6 month study in subjects with type 1 diabetes, alterations in 
the glucose pharmacodynamics with inhaled human insulin were not observed 
 
Information on Clinical Trials 
 
Controlled clinical trials in type 1 or type 2 diabetes have shown that EXUBERA achieves and 
maintains effective glycaemic control comparable to subcutaneously administered fast-acting human 
insulin.  
 

   

M
ea

n 
G

IR
 (%

 o
f M

ax
im

um
)   

Time (min)   
(

SC Lispro (18 U)   
Exubera (6mg)  

)
Fast-acting 
Human Insulin 
(18 U) 

  



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Type 1 Diabetes  
 
In clinical trials in type 1 diabetes, patients using a regimen of EXUBERA in combination with long- 
or intermediate-acting insulin had similar reductions in HbA1c compared with patients taking 
subcutaneous insulin alone. The percentage of patients who achieved a goal of HbA1c < 7.0% was 
comparable between the treatment groups. 
 
Fasting plasma glucose levels were significantly lower in patients treated with regimens including 
EXUBERA compared with those treated with subcutaneously administered fast-acting human insulin 
only regimens.  
 
Type 2 Diabetes 
 
Patients in a clinical trial for type 2 diabetes, who used a regimen of EXUBERA in combination with 
long- or intermediate-acting insulin, had similar changes in HbA1c compared with patients treated 
with subcutaneous insulin alone.  
 
Fasting plasma glucose levels were significantly lower in patients treated with EXUBERA regimens 
compared with those treated with subcutaneous insulin.  
 
In clinical trials involving patients with type 2 diabetes not sufficiently controlled with oral agents 
alone, patients using a regimen of EXUBERA alone or in combination with oral agents, had greater 
improvements in HbA1c compared with patients treated with oral agents alone. In most of these 
studies the percentages of patients achieving HbA1c < 7.0% were higher for patients using a regimen 
including EXUBERA compared to patients on oral agents alone. Fasting plasma glucose was similar 
to or lower in patients using a regimen including EXUBERA compared to patients treated with oral 
agents alone. In patients with type 2 diabetes sufficiently controlled with oral agents the glycaemic 
control was not further improved by inhaled insulin. 
 
FEV1 decline 
 
Randomised, open label parallel group studies were conducted to examine FEV1 changes following 
initiation of EXUBERA therapy in type 1 and 2 subjects. Both EXUBERA and comparator treated 
subjects experienced declines in lung function over time during these trials (Figures 2 and 3). Small 
treatment group differences (favouring comparator) in change from baseline of 0.034L in type 1 and 
0.039L in type 2 occurred after 2 years of therapy. 
 
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated and 1.0% of 
comparator-treated type 1 subjects and in 5.0% of EXUBERA-treated and 3.4% of comparator-treated 
type 2 subjects. 
 



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 Figure 2. Observed Change from Baseline in FEV1 (L) in patients with type 1 diabetes mellitus. 
 

Figure 3. Observed Change from Baseline in FEV1 (L) in patients with type 2 diabetes mellitus. 
 
In Phase 2/3 trials, 9 out of 2498 subjects treated with EXUBERA were discontinued from trials due 
to a decline in pulmonary function whose end of study FEV1 showed a decline of ≥ 15% from 
baseline. These subjects experienced an average decrease in FEV1 of 21% (range 16%-33%) from 
baseline and were treated with EXUBERA for an average of 23 months. 6 of these discontinued 
subjects underwent follow-up pulmonary function testing. Of these patients, 5 exhibited a significant 
improvement in FEV1 following discontinuation of therapy and one subject did not decrease further 
from the end of study value. No further information is available for the remaining 3 subjects who 
discontinued. 
 

-0 .5
-0 .45

-0 .4

-0 .35

-0 .3
-0 .25

-0 .2

-0 .15
-0 .1

-0 .05
0

0 .05

0 .1

0 .15
0 .2

0 .25

0 .3
IN H
C o mp arato r

C
ha

ng
e 

fr
om

 B
as

el
in

e 
in

 F
E

V
1

(L
) 

( M
ea

n 
+/

-
S

D
)

N=Number of Subjects at Baseline, week 12, week 24, week 36 , week 48, week 60 , week 72 , 
week 84 , week 96, LOCF.
INH N= 236, 231, 233, 233, 235, 235, 226, 217, 208, 236. Comparator N= 253, 238, 252, 248, 
252, 249, 230, 224, 216, 253.

Baseline 12 24 36 48 60 72 84 96 LOCF

Visit (weeks)

C
ha

ng
e 

fr
om

 B
as

el
in

e 
in

 F
E

V
1

(L
) 

( M
ea

n 
+/

-
S

D
)

-0.5
-0.45

-0.4
-0.35

-0.3
-0.25

-0.2
-0.15

-0.1
-0.05

0
0.05

0.1
0.15

0.2
0.25

0.3

Baseline 24 36 52 65 78 91 104 +6 +12

Visit (weeks)

INH
Comparator
INH Washout

N=Number of Subjects at Baseline, week 52, week 104, week +6, week +12.
INH and INH washout N=158, 155, 143, 139, 123. Comparator N=145, 143, 125, 129, 120.

Comparative Phase Washout Phase



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0

10

20

30

40

50

60

70

80

0 30 60 90 120 150 180 210 240 270 300 330 360

T im e  (m in )

C
h

an
ge

 F
ro

m
 B

as
el

in
e 

S
er

um
 F

re
e 

In
su

lin
 

C
on

ce
n

tr
at

io
n 

(u
U

/m
l) Inha le d Insulin

Sub cuta neo us Insuli n

FEV1 reversibility 
 
In type 1 subjects, resolution of small treatment group differences (0.010L favouring comparator) 
occurred within 2 weeks of EXUBERA cessation following 12 weeks of therapy. In type 2 subjects, 
resolution of small treatment group differences (0.039L favouring comparator) occurred within 6 
weeks of EXUBERA cessation following 2 years of therapy (Figure 3). In a smaller group (n=36) of 
mixed type 1 and 2 subjects treated with EXUBERA for > 36 months, cessation of therapy resulted in 
a mean FEV1 increase of 0.036L over the subsequent 6 months. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Inhaled human insulin is delivered by the pulmonary route. Inhaled human insulin is absorbed as 
rapidly as fast-acting insulin analogues and more rapidly than subcutaneously administered fast-acting 
human insulin in healthy subjects and in subjects with type 1 or type 2 diabetes (see Figure 4). 
 
Figure 4: Mean changes in serum free insulin concentrations (µU/mL) after inhalation of 4mg of 
human insulin or subcutaneous injection of 12 IU fast-acting human insulin in obese subjects with 
type 2 diabetes. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The time to peak insulin concentration (Tmax) is generally half of that for subcutaneously administered 
fast-acting human insulin. Peak insulin concentration is reached generally by 45 minutes for inhaled 
human insulin. Intrasubject variability of time to peak insulin concentrations was less for inhaled 
human insulin than for subcutaneous fast-acting human insulin in subjects with type 1 or 2 diabetes. 
 
In subjects with type 1 diabetes mellitus, inhaled human insulin had a comparable intrasubject 
variability of AUC to subcutaneously administered fast-acting human insulin. For Cmax, the 
intrasubject variability of inhaled insulin is greater than that of subcutaneously administered fast-
acting human insulin. In obese subjects with type 2 diabetes, intrasubject variability was comparable 
to or less than that of subcutaneously administered fast-acting human insulin for Cmax and AUC. 
 
The relative bioavailability of EXUBERA compared to subcutaneous fast-acting human insulin is 
approximately 10%. Unlike subcutaneous insulin preparations, the bioavailability of EXUBERA is 
not influenced by Body Mass Index. 
 
In a study in healthy subjects, systemic exposure (AUC and Cmax) of inhaled human insulin 

EXUBERA (4mg) 



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increased in an approximately dose proportional fashion from 1 mg to 6 mg when a maximum of two 
blisters from either strength or their combination was administered. In a study where the dosage form 
of three 1 mg blisters was compared with one 3 mg blister, Cmax and AUC of inhaling three 1 mg 
blisters were approximately 30% and 40% greater, respectively, than that of inhaling from one 3 mg 
blister, indicating that three 1 mg blisters are not interchangeable with one 3 mg blister (see sections 
2, 4.2 and 4.4).  
 
An approximately 40% higher bioavailability of three 1 mg unit dose blisters compared to one 3 mg 
unit dose blister was observed in healthy subjects. An explanation for the differences in 
bioavailability appears to be the different energy to mass ratio between the 1 and 3 mg unit blisters 
since with less powder in the blister the inhaler is more efficient in breaking up or de-agglomerating 
the powder leading to a larger proportion of smaller aerodynamic particle sizes for the 1 mg blister 
(see sections 2 and 4.4). 
 
Distribution 
 
Following oral inhalation of a single dose of human insulin approximately 30% of the total blister 
content remains in the blister or device, 20% is deposited in the oropharynx, 10% in the conducting 
airways and 40% reaches the deep lung.   
 
Animal studies did not show that inhaled human insulin accumulates in the lung. 
 
Special Populations 
 
Smoking 
 
Smoking greatly increases the rate and extent of absorption of inhaled human insulin (Cmax about 3 to 
5 times and AUC about 2 to 3 times higher) and therefore could increase the risk of hypoglycaemia 
(see sections 4.3 and 4.5).  
 
When EXUBERA was administered to healthy volunteers following 2-hours of passive exposure to 
cigarette smoke in a controlled experimental setting, insulin AUC and Cmax were reduced by 
approximately 17 and 30%, respectively (see section 4.5). 
 
Respiratory Diseases (Underlying Lung Disease) 
 
In non-diabetic subjects with mild to moderate asthma, AUC and Cmax for inhaled human insulin in 
the absence of treatment with a bronchodilator was slightly less than in subjects without asthma. 
 
In non-diabetic subjects with COPD, the absorption of inhaled human insulin appeared greater 
compared with that in subjects without COPD (see section 4.4).   
 
Administration of salbutamol 30 minutes prior to EXUBERA in non-diabetic subjects with mild-
moderate asthma resulted in an increase in insulin AUC and Cmax of between 25 and 51% compared to 
when EXUBERA was administered alone (see sections 4.2 and 4.5).  
 
Administration of fluticasone 30 minutes prior to EXUBERA did not affect the pharmacokinetics of 
EXUBERA in non-diabetic subjects with mild-moderate asthma (see section 4.5).    



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Renal impairment 
 
The effect of renal impairment on the absorption of inhaled human insulin has not been studied (see 
section 4.2). 
 
Hepatic impairment 
 
The effect of hepatic impairment on the absorption of inhaled human insulin has not been studied (see 
section 4.2). 
 
Gender 
 
In subjects with diabetes and in subjects without diabetes, no apparent differences in absorption of 
inhaled human insulin were observed between men and women. 
 
Children and adolescents 
 
In children (6-11 years) and adolescents (12-17 years) with type 1 diabetes, inhaled human insulin 
was absorbed more rapidly than fast-acting human insulin. Bioavailability of inhaled human insulin 
relative to subcutaneously administered fast-acting human insulin was comparable to that of adult 
subjects with type 1 diabetes (see section 4.2). 
 
Elderly 
 
In older subjects with type 2 diabetes, inhaled human insulin was absorbed more rapidly than 
subcutaneously administered fast-acting human insulin.  Bioavailability of inhaled human insulin 
relative to subcutaneously administered fast-acting human insulin was comparable to those in younger 
adult subjects with type 2 diabetes. 
 
5.3 Preclinical safety data 
 
Inhalation toxicity studies in rats and monkeys for up to 6 months gave no evidence for a special risk 
to the respiratory tract due to insulin inhalation powder. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Glycine 
Sodium Citrate (as dihydrate) 
Sodium Hydroxide 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
 
After first opening the foil overwrap: 3 months. 



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6.4 Special precautions for storage 
 
Store below 30oC. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25oC.  
 
Do not refrigerate or freeze the unit dose blisters. 
 
The inhaler and its components should be stored and used in a dry place. 
 
Do not refrigerate or freeze the insulin inhaler. 
 
6.5    Nature and contents of container 
 
One blister card contains 6 perforated unit dose blisters (PVC/Aluminium). Five blister cards are in a 
clear plastic (PET) thermoformed tray with a desiccant and covered with a clear plastic (PET) lid. The 
tray is sealed in a foil laminate pouch with a desiccant. 
 
Packaging sizes supplied: 
 
• Cardboard box containing 30 x 1 PVC/Aluminium perforated unit dose blisters (1 pouch)  
 
• Cardboard box containing 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches)  
 
• Cardboard box containing 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches) 
 
• Cardboard box containing 180 x 1 PVC/Aluminium perforated unit dose blisters (6 pouches)  
 
• Cardboard box containing 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches)  
 
• Cardboard box containing 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches) and 

2 spare Insulin Release Units (IRU) 
 
• Cardboard box containing 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches) and 

2 spare Insulin Release Units (IRU) 
 
• Cardboard box containing 180 x 1 PVC/Aluminium perforated unit dose blisters (6 pouches) 

and 2 spare Insulin Release Units (IRU) 
 
• Cardboard box containing 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches) 

and 6 spare Insulin Release Units (IRU) 
 
• A kit containing 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches), 1 insulin 

inhaler, 1 spare chamber and 6 spare Insulin Release Units (IRU) 
 
Additional insulin inhaler, insulin release units and chamber packages are available. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
EXUBERA unit dose blisters must only be used with the insulin inhaler.  
 
The insulin inhaler should be replaced annually. 
 



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The Insulin Release Unit (IRU) should be replaced once every 2 weeks. 
 
If the insulin inhaler is inadvertently exposed to extremely moist conditions during use this usually 
leads to a subsequent decreased the insulin dose delivered from the inhaler. In this case, the Insulin 
Release Unit (IRU) must be changed prior to the next inhalation (see section 4.4). 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
Ramsgate Road, Sandwich,  
Kent, CT13, 9NJ 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/327/009 
EU/1/05/327/010 
EU/1/05/327/011 
EU/1/05/327/012 
EU/1/05/327/013 
EU/1/05/327/014 
EU/1/05/327/015 
EU/1/05/327/016 
EU/1/05/327/017 
EU/1/05/327/018 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
24/01/2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 



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ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND MANUFACTURING 
AUTHORISATION HOLDER(S) RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 



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A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Pfizer Manufacturing Frankfurt GmbH & Co. KG 
Industry Park Hoechst 
65926 Frankfurt am Main 
Germany 
 
Name and address of the manufacturer responsible for batch release 
 
Heinrich Mack Nachf. GmbH & Co. KG 
Heinrich Mack Strasse 35 
89257 Illertissen 
Germany 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription. 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
� The Marketing Authorisation Holder must implement nationally an educational plan, prior to 

marketing, and as agreed with the competent authorities in the Member States. 
 
As part of this plan, the Marketing Authorisation Holder will provide health care professionals with 
educational materials for healthcare professionals and patients that are aimed at risk minimisation and 
will support safe and effective use for the product by the patient. 
 
Educational material shall consist of information aiming to minimise adverse events and support 
effective use through adequate education about:  
a) The need for consistent and standard inhalation technique to ensure both optimal and consistent 

product delivery 
b) Special precaution with the insulin inhaler 
c) Hypoglycemia 
d) 1 mg and 3 mg dose inequivalence 
e) Magnitude of titration steps and resulting precautions  
f) The change in pulmonary function and the need for pulmonary function monitoring 
g) Smoking in relation to induced alteration in pharmacokinetics 
h) Rare pulmonary events 
i) Increased insulin antibody levels 
j) Recommendation for special populations; underlying lung diseases such as asthma and COPD, 

congestive heart failure, pregnancy, children and adolescent 



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• OTHER CONDITIONS 
 
The MAH must ensure that the system of pharmacovigilance is in place and functioning before the 
product is placed on the market. 
 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the Pharmacovigilance Plan. 
 
An updated Risk Management Plan, as per the CHMP Guideline on Risk Management Systems for 
medicinal products for human use, should be submitted at the same time as the PSURs, within 60 days 
of an important (Pharmacovigilance or Risk minimisation) milestone being reached or when the 
results of a study becoming available or at the request of the Competent authority. 

 
 

 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton/Unit dose blisters (30, 60, 90, 180 and 270) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 1 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each unit dose blister contains 1 mg insulin human.  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: Mannitol, glycine, sodium citrate (as dihydrate), sodium hydroxide 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
30 x 1 perforated unit dose blisters 
60 x 1 perforated unit dose blisters 
90 x 1 perforated unit dose blisters 
180 x 1 perforated unit dose blisters 
270 x 1 perforated unit dose blisters 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
For use only with the insulin inhaler. 
Read package leaflet and instructions for use of the inhaler before use. 
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 



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8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 30˚C. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25˚C. Use within 3 months of opening. 
 
Do not refrigerate or freeze. 
 
 
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 
 
Pfizer Limited 
Ramsgate Road 
Sandwich 
Kent 
CT13 9NJ 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
EU/1/05/327/001 
EU/1/05/327/002 
EU/1/05/327/003 
EU/1/05/327/004 
EU/1/05/327/005 
 
 
13. BATCH NUMBER 
 
BN: {number} 
 



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14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
EXUBERA 1 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
{NATURE/TYPE} 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 1 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
 
 
3. EXPIRY DATE 
 
EXP{MMYYYY} 
 
 
4. BATCH NUMBER 
 
Lot{number} 
 
 
5. OTHER 
 



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MINIMUM PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
FOIL OVERWRAP 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
EXUBERA 1 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
30x 1 perforated unit dose blisters 
 
 
3. METHOD AND ROUTE(S) OF ADMINSTRATION 
 
Inhalation use  
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
4. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
5. NAME OF MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
 
6. BATCH NUMBER 
 
Lot{number} 
 
 
7. OTHER 
 
 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton/Unit dose blisters (60, 90, 270) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 1 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each unit dose blister contains 1 mg insulin human. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: Mannitol, glycine, sodium citrate (as dihydrate), sodium hydroxide 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
Box containing: 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches) and 2 spare Insulin 
Release Units (IRU) 
 
Box containing: 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches) and 6 spare Insulin 
Release Units (IRU) 
 
Box containing: 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches), 1 insulin inhaler, 1 
spare chamber and 6 spare Insulin Release Units (IRU) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
For use only with the insulin inhaler. 
Read package leaflet and instructions for use of the inhaler before use. 
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



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8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 30˚C. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25˚C. Use within 3 months of opening. 
 
Do not refrigerate or freeze. 
 
 
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 
 
Pfizer Limited 
Ramsgate Road 
Sandwich 
Kent 
CT13 9NJ 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/327/006 
EU/1/05/327/007 
EU/1/05/327/008 
 
 
13. BATCH NUMBER 
 
BN: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
EXUBERA 1 mg 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton/Unit dose blisters (30, 60, 90, 180 and 270) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 3 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each unit dose blister contains 3 mg insulin human. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: Mannitol, glycine, sodium citrate (as dihydrate), sodium hydroxide 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
30 x 1 perforated unit dose blisters 
60 x 1 perforated unit dose blisters 
90 x 1 perforated unit dose blisters 
180 x 1 perforated unit dose blisters 
270 x 1 perforated unit dose blisters 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
For use only with the insulin inhaler. 
Read package leaflet and instructions for use of the inhaler before use. 
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 



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9. SPECIAL STORAGE CONDITIONS 
 
Store below 30˚C. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25˚C. Use within 3 months of opening. 
 
Do not refrigerate or freeze. 
 
 
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 
 
Pfizer Limited 
Ramsgate Road 
Sandwich 
Kent 
CT13 9NJ 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/327/009 
EU/1/05/327/010 
EU/1/05/327/011 
EU/1/05/327/012 
EU/1/05/327/013 
 
 
13. BATCH NUMBER 
 
BN: {number} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
EXUBERA 3 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
{NATURE/TYPE} 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 3 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
 
 
3. EXPIRY DATE 
 
EXP{MMYYYY} 
 
 
4. BATCH NUMBER 
 
Lot{number} 
 
 
5. OTHER 
 



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MINIMUM PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING  
 
FOIL OVERWRAP 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
EXUBERA 3 mg inhalation powder pre-dispensed 
 
Insulin human 
 
 
2. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
30x 1 perforated unit dose blisters 
 
 
3. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use  
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
4. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
5. NAME OF MARKETING AUTHORISATION HOLDER 
 
Pfizer Limited 
 
 
6. BATCH NUMBER 
 
Lot{number} 
 
 
7. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton/Unit dose blisters (60, 90, 180, 270) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EXUBERA 3 mg inhalation powder pre-dispensed 
Insulin human 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each unit dose blister contains 3 mg insulin human. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: Mannitol, glycine, sodium citrate (as dihydrate), sodium hydroxide 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder pre-dispensed 
 
Box containing: 60 x 1 PVC/Aluminium perforated unit dose blisters (2 pouches) and 2 spare Insulin 
Release Units (IRU) 
 
Box containing: 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches) and 2 spare Insulin 
Release Units (IRU) 
 
Box containing: 180 x 1 PVC/Aluminium perforated unit dose blisters (6 pouches) and 2 spare Insulin 
Release Units (IRU) 
 
Box containing: 270 x 1 PVC/Aluminium perforated unit dose blisters (9 pouches) and 6 spare Insulin 
Release Units (IRU) 
 
Box containing: 90 x 1 PVC/Aluminium perforated unit dose blisters (3 pouches), 1 insulin inhaler, 1 
spare chamber and 6 spare Insulin Release Units (IRU) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
For use only with the insulin inhaler. 
Read package leaflet and instructions for use of the inhaler before use. 
 
Do not substitute three 1 mg blisters for one 3 mg blister. If 3 mg blisters are unavailable, use only 
two 1 mg blisters as replacement. 
 
 
 
 



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6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP: {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 30˚C. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: Store below 25˚C. Use within 3 months of opening. 
 
Do not refrigerate or freeze. 
 
 
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 
 
Pfizer Limited 
Ramsgate Road 
Sandwich 
Kent 
CT13 9NJ 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/327/014 
EU/1/05/327/015 
EU/1/05/327/016 
EU/1/05/327/017 
EU/1/05/327/018 
 
 
13. BATCH NUMBER 
 
BN: {number} 
 
 



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14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
EXUBERA 3 mg 



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B. PACKAGE LEAFLET 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

EXUBERA 1 mg inhalation powder pre-dispensed 
EXUBERA 3 mg inhalation powder pre-dispensed 

Insulin human 
 

Read all of this leaflet carefully before you start taking this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have further questions, please ask your doctor, diabetes nurse or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What EXUBERA is and what it is used for 
2. Before you take EXUBERA 
3. How to take EXUBERA 
4. Possible side effects 
5 How to store EXUBERA 
6. Further information 
 
Taking three separate 1 mg unit dose blisters delivers more insulin to your lungs than a single 3 mg 
unit dose blister does. Three 1 mg unit dose blisters should not be substituted for one 3mg blister (see 
section 2, “Take special care with EXUBERA”, section 3, “How to take EXUBERA” and section 6 
“Further information”). 
 
A unit dose blister is the individual container in which the insulin powder is packaged and will be 
called a blister in the rest of this leaflet. 
 
 
1. WHAT EXUBERA IS AND WHAT IT IS USED FOR 
 
EXUBERA is an inhalation powder contained in blisters. The contents of the blisters should be 
breathed in through your mouth into your lungs using the insulin inhaler. 
 
EXUBERA is an anti-diabetic agent that lowers your blood sugar. 
 
EXUBERA is a fast-acting insulin. This means that it will start to lower your blood sugar 10-20 
minutes after you take it, with a maximum effect at 2 hours and the effect will last for around 6 hours. 
 
EXUBERA is often given in combination with other diabetes treatments.  
 
EXUBERA is used to reduce high blood sugar in adult patients with type 2 diabetes mellitus who 
need insulin.  
 
EXUBERA can also be used to treat type 1 diabetes in adults whose level of blood sugar is not well-
controlled by insulin injections.  
 
Diabetes is a disease in which your body does not produce enough insulin to control the level of blood 
sugar. 
 
 



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2. BEFORE YOU TAKE EXUBERA 
 
Do not take EXUBERA 
 
• If you feel hypoglycaemia (low blood sugar) coming on. See the information at the end of 

section 4 “Possible side effects” of this leaflet for further advice.  
• If you are allergic to insulin, the active ingredient contained in EXUBERA or any of the other 

ingredients of EXUBERA. If you suspect an allergy to EXUBERA, speak to your doctor 
immediately.  

• If you smoke, or if you have smoked in the last six months you must not take EXUBERA as 
you may have extra risk of hypoglycaemia (very low blood sugar). Please speak to your doctor 
immediately if you take EXUBERA and resume smoking or have smoked in the last 6 months 
before starting to take EXUBERA. 

• If you have poorly controlled , unstable, or severe asthma. 
• If you have severe (GOLD stage III or IV), Chronic Obstructive Pulmonary Disease (COPD). 
 
Take special care with EXUBERA 
 
Please follow closely the instructions for dosage, monitoring (blood and urine tests), diet and physical 
activity (physical work and exercise) as discussed with your doctor or nurse. 
 
Before you start taking EXUBERA your doctor or nurse will tell you how to use the inhaler properly. 
Please also read the “Instructions for Use” of the inhaler at the end of the package leaflet carefully 
before taking EXUBERA. Make sure that you can use the inhaler properly as this could affect the 
amount of insulin you breathe in.  
 
You should avoid taking EXUBERA in moist conditions e.g. a bathroom following a steamy shower 
as this will usually give you a lower insulin dose than you need (see “Instructions for Use” at the end 
of the package leaflet for advice).  
 
If you accidentally expose your inhaler to moist conditions during use, this will usually decrease the 
dose of insulin you take. In this case you must change the Insulin Release Unit (IRU) prior to your 
next inhalation. 
 
Dosing 
 
Your doctor will prescribe your starting pre-meal dose of EXUBERA based on your body weight. 
This may include a mix of 1 mg (green coloured) and 3 mg (blue coloured) blisters.  It is important to 
follow your doctor’s instructions exactly. 
 
A 1 mg unit dose blister is approximately equal to 3 IU of fast-acting subcutaneous insulin and a 3 mg 
unit dose blister is approximately equal to 8 IU of fast-acting subcutaneous insulin. 
 
Dose adjustments may be required based on meal size and nutrient composition, time of day (higher 
insulin requirements in the morning), pre-meal blood glucose concentration, recent or planned 
exercise. 
 
Do not use three separate 1 mg blisters in place of one 3 mg blister, as this will give you a much 
higher insulin dose (see “How to take EXUBERA” for further advice). 
 
If you have low body weight check with your doctor if you can use EXUBERA. If you need dose 
titrations of less than 1 mg it is recommended you do not use EXUBERA (see section 3 “How to take 
EXUBERA” for further advice and section 6 “Further information”). 
 



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Special patient groups 
 
If your liver or kidneys do not function well speak to your doctor, who may advise that you use lower 
insulin doses. 
If you are under 18 years of age, please speak to your doctor, as use of EXUBERA is not 
recommended for patients under 18 years of age. 
 
There is little experience with EXUBERA in patients older than 75 years. 
 
There is very little experience with EXUBERA in patients with congestive heart failure. EXUBERA 
is not recommended if you have breathing difficulties with congestive heart failure. 
 
Lung diseases 
 
Talk to your doctor if you have any lung disease such as asthma, emphysema or chronic bronchitis. 
EXUBERA is not recommended for patients with lung disease. Also, if you experience breathing 
difficulties that you have not previously discussed with your doctor, you should discuss them before 
starting EXUBERA treatment.  
 
Before starting treatment your doctor will carry out a simple test on your lung function to decide 
whether EXUBERA is the right treatment for you.  Once you start treatment, your doctor will check 
your lung function again after 6 months and at other times to see how well you are tolerating 
EXUBERA. 
 
If you notice an immediate and severe worsening of your breathing soon after taking a dose of 
EXUBERA, you should stop taking EXUBERA and tell your doctor immediately or go to the casualty 
department at your nearest hospital. 
 
You should also tell your doctor if you develop any other increasing breathing difficulties while 
taking EXUBERA. 
 
Illness and injuries 
 
If you are ill or have a major injury, then your blood sugar may increase (hyperglycaemia) or if you 
are not eating enough your blood sugar may become too low (hypoglycaemia). In such situations, the 
management of your diabetes may require a lot of care and you may need to seek advice from your 
doctor or nurse.  
 
If you have infection in your airways (such as bronchitis or upper respiratory tract infection) while 
taking EXUBERA you should monitor your blood glucose frequently and you may need to adjust 
your EXUBERA dose. Please talk to your doctor if you have problems administering EXUBERA or 
controlling your blood glucose. There is no experience with EXUBERA in patients with infection of 
the deep lung (pneumonia). 
 
Please see the end of section 4 for important information about hypoglycaemia and hyperglycaemia 
and its treatment. 
 
Travel 
 
Before travelling, consult your doctor or nurse to talk about timings of meals and insulin 
administration while travelling, the possible effects of changing to different time zones on blood sugar 
levels and control and the availability of EXUBERA in the countries you are visiting. 
 



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Taking other medicines 
 
Some medicines cause the blood sugar level to fall, some cause it to rise, others may have both 
effects, depending on the situation. In each case, it may be necessary to adjust your insulin dosage to 
avoid too low or too high blood sugar levels. Be careful not only when you start another medicine, but 
also when you stop it.  
 
Tell your doctor about all medicines that you are taking, including those you have bought without a 
prescription (such as from a Pharmacy or other shop). Before taking a medicine ask your doctor if it 
can affect your blood sugar level, and what action, if any, you need to take. 
 
Medicines that may cause your blood sugar to fall include diabetes tablets, angiotensin converting 
enzyme (ACE) inhibitors (used for the treatment of certain heart conditions, high blood pressure or 
elevated protein/albumin in the urine), monoamine oxidase (MAO) inhibitors (used 
for the treatment of depression), certain beta-blockers (used for the treatment of certain heart 
conditions and high blood pressure), salicylates (e.g. aspirin, used to relieve pain and lower fever) and 
sulphonamide antibiotics.  
 
Medicines that may cause your blood sugar to rise include corticosteroids (used to treat inflammatory 
conditions, except topical administration), danazol (used for the treatment of some female hormonal 
disorders), oral contraceptives (used for birth control), thyroid hormones (used for the treatment of 
malfunction of the thyroid gland), growth hormones (used in endocrine conditions), sympathomimetic 
agents (used for the treatment of asthma) and thiazides (used in special endocrine conditions).  
 
The use of a bronchodilator (reliever inhaler) for asthma or other airway conditions may cause a more 
pronounced fall in blood sugar in response to inhaled insulin (see section 2 “Do not take EXUBERA” 
and section 2 “Take special care with EXUBERA”). 
 
Your blood sugar level may either fall or rise if you take beta-blockers or drink alcohol.  Beta-
blockers may weaken the warning symptoms of a hypoglycaemic reaction or suppress them entirely.  
Alcohol may increase the action of insulin and cause low blood sugar levels. Octreotide/lanreotide 
(used in special endocrine conditions) may change the need for insulin. 
 
If you smoke, the amount of insulin your body absorbs will be increased and you will have a greater 
risk of hypoglycaemia.  If you are taking EXUBERA, do not smoke (see section 2, “Do not take 
EXUBERA”). 
 
In contrast, exposure to other people’s cigarette smoke may decrease the amount of insulin your body 
absorbs. 
 
Pregnancy and breast-feeding 
 
There is no experience on the use of EXUBERA in pregnant women. EXUBERA should not be taken 
during pregnancy. Inform your doctor or nurse if you are planning to become pregnant or if you are 
already pregnant. Your doctor may replace EXUBERA with an injectable insulin for your diabetes. 
Your insulin dosage may need to be changed during pregnancy and after giving birth. Careful control 
of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. 
 
If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and 
your diet. 



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Driving and using machines 
 
Your ability to concentrate or react may be reduced if you have too low blood sugar (hypoglycaemia). 
Please keep this possible problem in mind in all situations where you might put yourself and others at 
risk (e.g. driving a car or operating machinery). You should contact your doctor about the advisability 
of driving if you have: 
- frequent episodes of hypoglycaemia, 
- reduced or absent warning signs of hypoglycaemia. 
 
 
3. HOW TO TAKE EXUBERA 
 
EXUBERA should be taken within 10 minutes before the start of a meal. 
 
Your doctor will decide how much EXUBERA you will initially need based on your weight and 
recommend any changes after that based on your diet and amount of exercise. 
 
A 1 mg blister of EXUBERA gives you about the same insulin dose as 3 IU of subcutaneously 
injected fast-acting insulin human. A 3 mg blister of EXUBERA gives you about the same insulin 
dose as 8 IU of subcutaneously injected fast-acting insulin human. If you have low body weight check 
with your doctor if you can use EXUBERA. If you need dose titrations of less than 1 mg it is 
recommended you do not use EXUBERA. 
 
Always make sure you have the correct strength and number of EXUBERA blisters available before 
taking your dose. It is important that you take the number of 1 mg and 3 mg blisters that your doctor 
recommends in the combination that he or she recommends.  
 
Do not use three 1 mg blisters in place of one 3 mg blister, as this will give you a much higher 
dose of insulin. If you temporarily run out of 3 mg blisters, two 1 mg blisters should be used and 
you should monitor your blood glucose levels closely. You should contact your doctor or 
pharmacist as soon as possible to get more 3 mg blisters.  If you are unsure contact your doctor, 
nurse or pharmacist. 
 
Preparing to take EXUBERA 
 
To use an EXUBERA blister, first separate the blister from the spine by tearing along the tear line 
(perforation). 
 
Do not open the blister containing EXUBERA.  The blister will be punctured inside the inhaler when 
you use it.  Do not swallow the contents of the blister. 
 
EXUBERA should only be breathed in through your mouth and should only be taken with your 
insulin inhaler. 
 
Always follow your doctor’s instructions about when and how to take EXUBERA. Please see the 
“Instructions for Use” at the end of the package leaflet for advice on how to use your insulin inhaler, 
and how to care for it. Check with your doctor, nurse or pharmacist if you have any questions 
regarding EXUBERA or the insulin inhaler.  
 
Mistakes in dosage 
 
Please discuss with your doctor what you should do if you were to take too much or too little 
EXUBERA, or if you miss a dose, so that you know what to do. 
 
–If you have taken too much insulin, you may develop hypoglycaemia. Check your blood sugar 
frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood 



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sugar. For information on the treatment of hypoglycaemia, see the end of section 4 “Possible side 
effects”. 
 
–If you have missed a dose of insulin or if you have taken too low a dose, your blood sugar level 
may become too high. Check your blood sugar frequently. For further information on hyperglycaemia, 
see the end of section 4 “Possible side effects”. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, EXUBERA can have side effects, although not everybody gets them. 
 
Side effects reported very commonly  
(Seen in more than 1 in 10 patients) 
 
Hypoglycaemia - As with all insulin therapy, the most common side effect with EXUBERA is 
hypoglycaemia (too low blood sugar). Please see the end of this section for important further 
information about hypoglycaemia and its treatment. 
 
Cough - A cough may occur within seconds to minutes after inhaling EXUBERA. The cough is 
usually mild and often gets better over time. 
 
Side effects reported commonly 
(Seen in less than 1 in 10 but more than 1 in 100 patients) 
 
Commonly reported side effects are mild to moderate shortness of breath (dyspnoea), productive 
cough, throat irritation and dry throat. 
 
Side effects reported uncommonly 
(Seen in less than 1 in 100 but more than 1 in 1000 patients). 
 
Uncommon side effects are inflammation of the throat (pharyngitis), nose bleed (epistaxis), airway 
constriction with difficulties breathing (bronchospasm), wheezing, voice alteration (dysphonia), throat 
pain (pharyngolaryngeal pain), tonsillar disorder, dry mouth and chest pain. 
 
Other side effects 
 
Some patients have experienced fluid in the lung lining (pleural effusion). 
 
Insulin treatment can cause the body to produce antibodies to insulin (substances that bind to insulin).  
Development of such antibodies is seen more commonly in patients treated with EXUBERA 
compared to subcutaneous insulin. Although these antibodies may be produced, they do not have any 
effect on your blood glucose control. 
 
A small decrease in your lung function may occur during EXUBERA treatment, although you should 
not notice any symptoms. This change occurs within the first months of treatment and usually doesn’t 
worsen as you continue treatment. If you stop therapy with EXUBERA, your lung function will 
usually return to your normal level. If you notice a change in your breathing while taking EXUBERA 
inform your doctor. 
 
Severe allergic reactions to insulin are very rare. Such reactions to insulin or to the other ingredients 
can cause skin reactions, severe swelling of skin or mucous membranes (angio-oedema), shortness of 
breath, a fall in blood pressure and may become life threatening. 
 
Changes to your sight may occur upon starting insulin therapy. These changes are usually mild and go 
away with time. 



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Insulin treatment may also cause temporary build-up of water in the body with swelling in the calves 
and ankles. 
  
If any of these side effects get serious or if you notice any side effects not listed in this leaflet, 
please tell your doctor or pharmacist. 
 
If your blood sugar is too low (hypoglycaemia) 
Your blood sugar levels may fall too much, if for example: 
– you take too much insulin, 
– you miss meals or delay them, 
– you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances 
similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates), 
– you lose or are unable to consume carbohydrates due to vomiting or diarrhoea, 
– you drink alcohol, particularly if you are not eating much, 
– you take more physical exercise than usual or a different type of physical activity, 
– you are recovering from an injury or operation or other stress, 
– you are recovering from a feverish illness or from another illness, 
– you are taking or have stopped taking certain other medicines (see section 2, “Taking other 
medicines”). 
 
Hypoglycaemia (low blood sugar levels) are also more likely to occur if: 
– you have just begun insulin treatment or changed to another insulin preparation, 
– your blood sugar levels are almost normal or are unstable, 
– you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism. 
 
Symptoms that tell you that your blood sugar level is falling too much or too fast may be, for 
example: sweating, clammy skin, anxiety, fast heartbeat, high blood pressure, palpitations and 
irregular heartbeat, chest pain (angina pectoris). These symptoms often develop before the symptoms 
of a low sugar level in the brain. 
 
The following symptoms indicate a low sugar level in the brain: headaches, intense hunger, nausea, 
vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in 
concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of 
speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and 
tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after 
yourself, convulsions, loss of consciousness. 
 
The first symptoms which alert you to hypoglycaemia (“warning symptoms”) may change, be weaker 
or may be missing altogether if: 
– you are elderly,  
– you have had diabetes for a long time  
– due to diabetes, you suffer from a certain type of nervous disease (autonomic neuropathy), 
– you have recently suffered hypoglycaemia (e.g. the day before) or if it develops slowly, 
– you have almost normal or, at least, greatly improved blood sugar levels, 
– you are taking or have taken certain other medicines (see section 2, “Taking other medicines”). 
 
In such a case, you may develop severe hypoglycaemia (and even lose consciousness) before you are 
aware of the problem. Try always to keep familiar with your warning symptoms. If necessary, more 
frequent blood sugar testing can help to identify mild hypoglycaemic episodes that might otherwise be 
overlooked. While you are not confident about recognising your warning symptoms, avoid situations 
(e.g. driving a car) in which you or others would be put at risk by hypoglycaemia.  



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What to do in case of hypoglycaemia 
1. Do not take more insulin. Immediately take about 10 to 20 gram sugar, e.g. as glucose, sugar cubes 
or a sugar-sweetened drink. (Measure once as spoonfuls or lumps of sugar or glucose tablets to see 
how much this means). Caution: please remember that artificial sweeteners and foods with artificial 
sweeteners (e.g. diet drinks) are of no help in hypoglycaemia. 
2. Then eat something that has a long-acting effect in raising your blood sugar (e.g. bread). Your 
doctor or nurse will have discussed this with you. 
3. If the hypoglycaemia comes back again take another 10 to 20 gram sugar. 
4. Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs. 
 
Always carry some sugar (at least 20 grams) with you.  
If you are not able to swallow or if you are unconscious, you will require an injection of glucose or 
glucagon (a medicine which increases blood sugar). These injections may be justified even if it is not 
certain that you have hypoglycaemia. 
 
It is advisable to test your blood sugar immediately after taking glucose to check that you really have 
hypoglycaemia. 
 
If your blood sugar is too high (hyperglycaemia) 
Your blood sugar level may be too high, if for example: 
– you have not taken enough insulin, or if it has become less effective, e.g. through incorrect storage, 
– you are doing less physical exercise, you are under stress (emotional distress, excitement), or if you 
have an injury, operation, feverish illness or certain other diseases, 
– you are taking or have taken certain other medicines (see section 2, “Taking other medicines”). 
 
Symptoms that may tell you that your blood sugar levels are too high: 
thirst, increased need to pass water, tiredness, dry skin, reddening of the face, loss of appetite, low 
blood pressure, fast heartbeat, and glucose and ketone bodies in urine may be signs of too high blood 
sugar. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs 
of a serious condition (ketoacidosis) resulting from lack of insulin. 
 
Test your blood sugar level and your urine for ketones as soon as any such symptoms of 
hyperglycaemia occur as described above. Severe hyperglycaemia or ketoacidosis must always be 
treated by a doctor, normally in a hospital. 
 
Carry some information with you to show you are diabetic. 
 
 
5. HOW TO STORE EXUBERA 
 
Keep out of the reach and sight of children. 
 
Store below 30°C. Store in the original package in order to protect from moisture. 
 
After opening the foil overwrap: store below 25oC and use within 3 months of opening.  
Do not refrigerate or freeze the blisters. 
 
Do not use EXUBERA if you notice that a blister is not properly sealed or damaged. 
 
Do not use EXUBERA after the expiry date (EXP) stated on the pack or unit dose blisters. 
 
For instructions on how to look after your insulin inhaler see “Instructions for Use” at the end of the 
package leaflet. 



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6. FURTHER INFORMATION 
 
What EXUBERA contains 
 
- The active substance is insulin human. Each unit dose blister contains 1 mg or 3 mg of the 

active substance insulin human. 
- The other ingredients are: mannitol, glycine, sodium citrate (as dihydrate) and sodium 

hydroxide. 
 
Taking three separate 1 mg blisters delivers more insulin to your lungs than a single 3 mg blister does. 
Three 1 mg blisters should not be substituted for one 3 mg blister (see section 2, “Take special care 
with EXUBERA” and section 3, “How to take EXUBERA”). 
 
What EXUBERA looks like and contents of the pack 
 
EXUBERA is an inhalation powder, pre-dispensed, and is supplied as tear-off unit dose blisters 
marked with either ‘1 mg EXUBERA’ with green ink or ‘3 mg EXUBERA’ with blue ink. For the 
1 mg product, the spine of the blister card has one raised ridge with the individual blisters embossed 
with one raised dot each. For the 3 mg product, the spine of the blister card has three raised ridges 
with the individual blisters embossed with three raised dots each. There are 6 blisters on each card 
and 5 cards per tray. The tray is sealed in a plastic foil pouch with a desiccant, which keeps the 
medicine dry and should not be eaten. 
 
EXUBERA is available in the following pack sizes: 
 
• A pack containing 30, 60, 90, 180 and 270 x 1 of 1 mg PVC/Aluminium perforated unit dose 

blisters  
 
• A pack containing 30, 60, 90, 180 and 270 x 1 of 3 mg PVC/Aluminium perforated unit dose 

blisters 
 
• A pack containing 60 x 1 of 1 mg PVC/Aluminium perforated unit dose blisters (2 pouches) 

and 2 spare Insulin Release Units (IRU) 
 
• A pack containing 270 x 1 of 1 mg PVC/Aluminium perforated unit dose blisters (9 pouches) 

and 6 spare Insulin Release Units (IRU) 
 
• A pack containing 60 x 1 of 3 mg PVC/Aluminium perforated unit dose blisters (2 pouches) 

and 2 spare Insulin Release Units (IRU) 
 
• A pack containing 90 x 1 of 3 mg PVC/Aluminium perforated unit dose blisters (3 pouches) 

and 2 spare Insulin Release Units (IRU) 
 
• A pack containing 180 x 1 of 3 mg PVC/Aluminium perforated unit dose blisters (6 pouches) 

and 2 spare Insulin Release Units (IRU) 
 
• A pack containing 270 x 1 of 3 mg PVC/Aluminium perforated unit dose blisters (9 pouches) 

and 6 spare Insulin Release Units (IRU) 
 
• A kit containing 90 x 1 of 1 mg PVC/Aluminium perforated unit dose blisters (3 pouches), 1 

insulin inhaler, 1 spare chamber and 6 spare Insulin Release Units (IRU) 
 
• A kit containing 90 x 1 of 3 mg PVC/Aluminium perforated unit dose blisters (3 pouches), 1 

insulin inhaler, 1 spare chamber and 6 spare Insulin Release Units (IRU) 
 



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Additional insulin inhaler, insulin release units and chamber packages are available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
The marketing authorisation holder is Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, 
United Kingdom. 
 
The manufacturer is Heinrich Mack Nachf. GmbH & Co. KG, Heinrich Mack Strasse 35, 89257, 
Illertissen, Germany. 
 
For any information about this medicine, please contact the local EXUBERA Customer Care Centre. 
 
België /Belgique / Belgien Luxembourg/Luxemburg 
Klanteninformatiedienst voor EXUBERA/ 
EXUBERA-Service-Center/Service Client local 
EXUBERA 
Tél/Tel: 0800 30432 
Tél/Tel: + 32 (0)2 554 62 11 
 

Service Client local EXUBERA/EXUBERA-
Service-Center 
Tél/Tel: 8002 5350 
Tél/Tel: + 32 (0)2 554 62 11 

�������	 Magyarország 
EXUBERA-������ �	 �	
��	 � ������  
���: 080014441 
���: +359 2 970 4333 
 

EXUBERA ügyfélszolgálat 
Tel. 06-80-203-279 
Tel.: + 36 1 488 37 00 


eská republika  Malta 
EXUBERA centrum pé�e o zákazníky 
Tel: 800106108 
Tel: + 420 283 004 111 
 

EXUBERA Customer Care Centre 
Tel:  800 62451 
Tel: + 356 21 220717 

Danmark Nederland 
EXUBERA kundecenter 
Tlf: 80 60 10 40 
Tlf: + 45 44 20 11 00 
 

Klanteninformatiedienst voor EXUBERA 
Tel: 0800 3982372 
Tel: + 31 (0)10 406 43 01 
 

Deutschland Norge 
EXUBERA-Service-Center  
Tel: 0800 3982372 
Tel: + 49 (0)721 6101 9000 
 

EXUBERA kundetelefon 
Tlf: 800 74444 
Tlf: + 47 67 52 61 00 
 

Eesti Österreich 
EXUBERA Kliendi Tugikeskus 
Tel: + 372 6 405 328 

EXUBERA-Service-Center  
Tel: 0800 80 80 42 
Tel: + 43 (0)1 521 15 0 
 

����� Polska 
������ ������������ � ! ���"��#��� 
$%& �'� ��� EXUBERA 
(�&: 80011 83333 
(�&: + 30 210 6785 797 
 

Lokalne telefoniczne centrum informacyjne dla 
pacjenta 
Tel.:  0800 80 88 80 
Tel.: + 48 22 335 61 00 



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España Portugal 
Centro local de Atención al Cliente de Exubera 
Tel: 900 900866 
Tel: + 34 91 490 99 00 
 

Serviço local de Atendimento ao utilizador de 
EXUBERA 
Tel: 800 206746 
Tel: + 351 21 423 5500 
 

France România 
Service Client local EXUBERA 
Tél: 0800 438 438 
Tél: + 33 (0)1 58 07 34 40 
 

EXUBERA – Centrul de Rela)ii cu Clien)ii 
Tel.: 0800 390 000 
Tel.: +40 (0)21 207 28 00 
 

Ireland Slovenija 
EXUBERA Customer Care Centre 
Tel: 1 800 882 392 
Tel: + 44 (0)1737 331111 
 

Center za svetovanje o zdravilu EXUBERA 
Tel: 080 2682 
Tel: + 386 1 52 11 400 

Ísland Slovenská republika 
EXUBERA neytendaþjónusta 
Tel:  044 20 11 00 
Tel: + 354 535 7000 
 

EXUBERA Centrum starostlivosti o pacientov 
Tel: 0800 101 001 
Tel: +421-2-3355 5500 

Italia Suomi/Finland 
Customer Care locale di EXUBERA 
Tel: 0800 021354 
Tel: + 39 06 33 18 21 
 

EXUBERA-asiakaspalvelunumero 
Puh/Tel: 0800 915 133 
Puh/Tel: + 358 (0)9 43 00 40 

������ Sverige  
������ ������������ � ! ���"��#��� 
$%& �'� ��� EXUBERA 
(�&: 800 92656 
(�&: +30 210 6785 798 
 

Kundservice för EXUBERA 
Tel: 020 88 80 80 
Tel: + 46 (0)8 5505 2000 

Latvija United Kingdom 
EXUBERA pacientu atbalsta centrs 
Tel: + 371 670 35 775 
 

EXUBERA Customer Care Centre 
Tel: 0845 850 0198 
Tel: + 44 (0)1737 331111 

Lietuva  
EXUBERA pacient* prieži+ros centras 
Tel: 8 800 22000 
Tel. + 3705 2514000 

 

 
This leaflet was last approved in   
 



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Insulin Inhaler Instructions for Use 
 
Read all of this leaflet carefully before starting to use your insulin inhaler 
 
Keep this leaflet.  You may need to read it again. 
 
Always make sure you have the correct blisters available before using your insulin inhaler. 
Also, read the Patient Information Leaflet for, EXUBERA 1 mg and 3 mg powder for inhalation pre-
dispensed. 
 
REPLACING YOUR INHALER AND THE INSULIN RELEASE (IRU)  
 
You should change your insulin inhaler once a year from the date you first use the inhaler.  
You should change the IRU in your insulin inhaler every 2 weeks. The IRU must be changed after 
accidental exposure to extremely moist conditions, e.g. steamy bathroom. 
 
HOW TO STORE YOUR INSULIN INHALER 
 
Keep out of the reach and sight of children. 
Store the insulin inhaler in a dry place at room temperature. 
 
Do not store the insulin inhaler in the refrigerator or freezer. 
 



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KNOW THE PARTS OF YOUR 
INSULIN INHALER 

 
 
HOW TO TAKE YOUR DOSE  
1. Set up your insulin inhaler  
Hold your insulin inhaler in your hand. Be sure 
that the word “EXUBERA” at the top faces you. 

 

Exubera Label 

Mouthpiece 

Chamber 

Insulin Release Unit  

Blue button 

(not visible) 

Chamber Release Button 

(not visible) 

Grey Button 

Insulin Blister 

Base 
Blue Handle 

Black Ring 

Chamber Release 

Button 



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Hold the black ring at the bottom of the base and 
use it to pull the base out of the chamber. 

 
You will hear a click when the inhaler is fully 
extended and locked into place.  The bottom of 
the chamber MUST be above the grey button. 

 
 

 
2. Load your insulin blister  
Hold the insulin blister by the tab with printed 
side up with the notch pointed towards the 
insulin inhaler, insert the blister. 
 
The 1 mg blister is printed with green ink and 
has one raised dot on the protruding end of each 
blister. 
The 3 mg blister is printed with blue ink and has 
three raised dots on the protruding end of each 
blister. 
 
The raised dots can be felt even when the blister 
is already inserted for reassurance that the 
correct dose is used. 
 

 

Slide the insulin blister straight into the blister 
slot as far as it will go. 

 



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3. Getting ready to take your dose  
Make sure that the mouthpiece is closed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pull out the blue handle as far as it will go. 
 
 
 
 
 
 
Squeeze the handle until it snaps shut. 

 
 

 

 
Stand or sit up straight. 
 
Breathe out normally. 

 



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4. Inhale your insulin dose  
Perform the following steps in immediate 
sequence. 
 
Hold the insulin inhaler upright with the blue 
button facing towards you.  Push the blue button 
until it clicks and watch for the insulin cloud to 
appear in the chamber. 

 
After the cloud appears, immediately turn the 
mouthpiece around.  The mouthpiece should now 
be facing towards you. 

 
Quickly form a seal with your lips around the 
mouthpiece so the insulin will not leak out. 
 
Do not block the opening of the mouthpiece with 
your tongue or teeth. Do not blow into the 
mouthpiece. 
 
Slowly and deeply breathe in the insulin cloud 
through your mouth in one breath.  

Do not blow into the mouthpiece. 
 
Take the mouthpiece out of your mouth. 
 
Close your mouth and hold your breath for 5 
seconds. 
 
Breathe out normally. 

 



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5. After your dose  
Turn the mouthpiece back to its closed position. 

 
Press the grey button and pull out the insulin 
blister. 
 
If you need another blister(s) as part of your 
dose, repeat steps 2, 3 and 4. 

 
6.  After your dosing is completed  
Squeeze the two chamber release buttons at the 
same time on the side of the base.  Push the base 
back into the chamber to store. 

 
HOW TO TAKE CARE OF YOUR INSULIN 
INHALER 

 

It is important to follow these steps so that your 
insulin inhaler stays clean and works properly. 

 

Take your insulin inhaler apart  
Hold the insulin inhaler in your hand.  Be sure 
that the word “EXUBERA” at the top faces you. 

 



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Hold the black ring at the bottom of the base and 
use it to pull the base out of the chamber. 

 
With one hand, squeeze the two chamber release 
Buttons at the same time on the side of the base 
while pulling the base all the way out of the 
chamber with the other hand. 

 
 
Cleaning  
Chamber and mouthpiece – once a week 

 
How 
Take your insulin inhaler apart. 

 
 

Turn the mouthpiece to the open position. See 
above. 

 



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Dampen a clean soft cloth and use mild liquid 
soap to wipe the outside and inside of the 
chamber and mouthpiece.  Do NOT put the 
chamber in the dishwasher. 

 

Thoroughly rinse the soap out of the chamber 
and mouthpiece with warm water. 

 

Allow to air dry.  Ensure that no water droplets 
remain, and then close the mouthpiece.  Reattach 
the chamber to the base. 

 

For instructions on how to attach the chamber to 
the base refer to the section “Put your  insulin 
inhaler together”. 

 

If the washed chamber is not dry prior to taking 
your next dose, use your spare chamber. 

 

Base - once a week 

 
 
How  
Do not put the base in water. 
 
Do not get the inside of the IRU wet. 
 
Do not use soap or any other cleanser. 
 
Dampen a clean soft cloth with water. 
 
While cleaning the top of the base be careful not 
to get any water into the IRU.  Do not take the 
IRU out at this time.  Keep the blue handle 
closed 
 
Wipe only the TOP and OUTSIDE surfaces of 
the Base.  Do not wipe the blister slot  



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Put your  insulin inhaler together  
Line the top of the base with the open end of the 
chamber.  The blue dot on the bottom of the 
chamber must be on the same side as the blue 
button. 
 
Squeeze the two chamber release buttons at the 
same time on the side of the base.  Push the base 
back into the chamber to store. 

 
Store your insulin inhaler in a dry place at room 
temperature. 

 

REPLACING YOUR INSULIN RELEASE 
UNIT (IRU) 

 

Change the IRU   
 
Every 2 weeks 
You should avoid taking EXUBERA in moist 
conditions e.g. a bathroom following a steamy 
shower as this will usually give you a lower 
insulin dose than you need (see package leaflet 
on the blisters for advice). 
If you accidentally expose your inhaler to moist 
conditions during use, this will usually decrease 
the dose of insulin you take. In this case you 
must change the IRU prior to you next 
inhalation. 

 

How  
Take out the used IRU 
While the chamber is removed from the base 
(see “Take your  insulin inhaler apart”), hold the 
base in your hand with the grey button facing 
you.  Turn the used IRU about a one-quarter turn 
counter clockwise towards the unlock symbol. 

 

 



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Pull the used IRU up and out of the base and 
discard.  
 
Dispose of the used IRU safely according to 
local requirements or check with your healthcare 
professional.  

 
Put in a new IRU 
 
Remove the IRU from its packaging. 
 
Hold the new IRU so the top is facing you.  You 
will see a blue line on it.  While holding the IRU 
with one hand, turn the top counter-clockwise as 
far as it will go. 

 

 
Line up the blue line on the top of the IRU with 
the unlock symbol on the top of the base. 
 
Push the IRU gently into the base.  Do not force, 
it should easily drop into place. (If the new IRU 
does not drop into place or fits tightly, remove 
and try again). 

 

Turn the top of the IRU clockwise until the blue 
line points to the lock symbol on the top of the 
base.  The new IRU is now locked in place. 

 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET