Ventavis

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml nebuliser solution 
Ventavis 20 microgram/ml nebuliser solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Ventavis 10 microgram/ml nebuliser solution 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 10 microgram iloprost. 
Each ampoule with 2 ml solution contains 20 microgram iloprost.  
 
Ventavis 20 microgram/ml nebuliser solution 
1 ml solution contains 20 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 20 microgram iloprost. 
 
Excipient with known effect 
• Ventavis 10 microgram/ml:  

Each ml contains 0.81 mg ethanol 96% (equivalent to 0.75 mg ethanol) 
• Ventavis 20 microgram/ml:  

Each ml contains 1.62 mg ethanol 96% (equivalent to 1.50 mg ethanol). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Nebuliser solution. 
 
Ventavis 10 microgram/ml nebuliser solution 
Clear, colourless solution. 
 
Ventavis 20 microgram/ml nebuliser solution 
Clear, colourless to slightly yellowish solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of adult patients with primary pulmonary hypertension, classified as NYHA functional 
class III, to improve exercise capacity and symptoms.  
 
4.2 Posology and method of administration 
 

Drug product Suitable inhalation device (nebuliser) to be used 

Ventavis 10 microgram/ml Breelib I-Neb AAD Venta-Neb  

Ventavis 20 microgram/ml Breelib I-Neb AAD  
 
Ventavis should only be initiated and monitored by a physician experienced in the treatment of 
pulmonary hypertension. 
 



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Posology 
 
Dose per inhalation session 
At initiation of Ventavis treatment the first inhaled dose should be 2.5 microgram iloprost as 
delivered at the mouthpiece of the nebuliser. If this dose is well tolerated, dosing should be increased 
to 5 microgram iloprost and maintained at that dose. In case of poor tolerability of the 5 microgram 
dose, the dose should be reduced to 2.5 microgram iloprost. 
 
Daily dose 
The dose per inhalation session should be administered 6 to 9 times per day according to the 
individual need and tolerability. 
 
Duration of treatment 
The duration of treatment depends on clinical status and is left to the physician’s discretion. Should 
patients deteriorate on this treatment intravenous prostacyclin treatment should be considered. 
 
Special populations 
 
Hepatic impairment 
Iloprost elimination is reduced in patients with hepatic dysfunction (see section 5.2). 
 
To avoid undesired accumulation over the day, special caution has to be exercised with these patients 
during initial dose titration. Initially, doses of 2.5 microgram iloprost should be administered using 
Ventavis 10 microgram/ml with dosing intervals of 3-4 hours (corresponds to administration of max. 
6 times per day). Thereafter, dosing intervals may be shortened cautiously based on individual 
tolerability. If a dose up to 5 microgram iloprost is indicated, again dosing intervals of 3-4 hours 
should be chosen initially and shortened according to individual tolerability. An accumulation of 
iloprost following treatment over several days is not likely due to the overnight break in 
administration of the medicinal product. 
 
Renal impairment 
There is no need for dose adaptation in patients with a creatinine clearance >30 ml/min (as 
determined from serum creatinine using the Cockroft and Gault formula). Patients with a creatinine 
clearance of ≤30 ml/min were not investigated in the clinical trials. Data with intravenously 
administered iloprost indicated that the elimination is reduced in patients with renal failure requiring 
dialysis. Therefore, the same dosing recommendations as in patients with hepatic impairment (see 
above) are to be applied. 
 
Paediatric population 
The safety and efficacy of Ventavis in children aged up to 18 years have not been established. 
No data from controlled clinical trials are available. 
 
Method of administration 
 
Ventavis is intended for inhalation use by nebulisation.  
 
To minimize accidental exposure it is recommended to keep the room well ventilated. 
 
The ready-to-use Ventavis nebuliser solution is administered with a suitable inhalation device 
(nebuliser) (see below and section 6.6).  
Patients stabilised on one nebuliser should not switch to another nebuliser without supervision by the 
treating physician as different nebulisers have been shown to produce aerosols with slightly different 
physical characteristics and delivery of the solution that may be faster (see section 5.2). 
 



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• Breelib 
 
Breelib is a small handheld, battery-powered, breath activated, vibrating mesh technology system. 
 
Ventavis 10 microgram/ml (1 ml ampoule) and Ventavis 20 microgram/ml nebuliser solution 
 
Ventavis 10 microgram/ml nebuliser solution (1 ml ampoule) delivers 2.5 microgram and Ventavis 20 
microgram/ml nebuliser solution delivers 5 microgram at the mouthpiece of the Breelib nebuliser. 
 
At initiation of Ventavis treatment or if the patient is switched from an alternative device, the first 
inhalation should be made with 1 ml ampoule of Ventavis 10 microgram/ml (see section 4.4). If 
inhalation with Ventavis 10 microgram/ml is well tolerated, the dose should be increased by using 
Ventavis 20 microgram/ml. This dose should be maintained. In case of poor tolerability of Ventavis 
20 microgram/ml, the dose should be reduced by using 1 ml ampoule of Ventavis 10 microgram/ml 
(see section 4.4). 
 
The duration of an inhalation session with Breelib nebuliser is approximately 3 minutes, which 
reflects the higher delivery rate of the Breelib compared to other nebulisers. 
 
Patients initiating Ventavis treatment or switching from an alternative device to Breelib should be 
closely supervised by the treating physician to ensure that dose and speed of inhalation are well 
tolerated. 
 
When using the Breelib nebuliser please follow the instructions for use provided with the device. 
Fill the medication chamber with Ventavis immediately before use. 
 
• I-Neb AAD 
 
The I-Neb AAD system is a portable, hand-held, vibrating mesh technology nebuliser system. This 
system generates droplets by ultrasound, which forces the solution through a mesh. The I-Neb AAD 
nebuliser has been shown to be suitable for the administration of Ventavis 10 microgram/ml (1 ml 
ampoule) and 20 microgram/ml nebuliser solution. The Mass Median Aerodynamic Diameter 
(MMAD) of the aerosol measured using I-Neb nebulising systems equipped with power level 10 disc 
was similar between Ventavis 20 microgram/ml (golden programme) and Ventavis 10 microgram/ml 
(purple programme) nebuliser solutions (i.e.: around 2 micrometres) but with faster delivery when 
using Ventavis 20 microgram/ml.  
 
The dose delivered by the I-Neb AAD system is controlled by the medication chamber in combination 
with a control disc. Each medication chamber is colour coded and has a corresponding colour coded 
control disc. 
 
Ventavis 10 microgram/ml nebuliser solution (1 ml ampoule) 
 
At initiation of Ventavis treatment with I-Neb system the first inhaled dose should be 2.5 microgram 
iloprost as delivered at the mouthpiece of the nebuliser using 1 ml ampoule of Ventavis 
10 microgram/ml. If this dose is well tolerated, dosing should be increased to 5 microgram iloprost 
using 1 ml ampoule of Ventavis 10 microgram/ml and maintained at that dose. In case of poor 
tolerability of the 5 microgram dose, the dose should be reduced to 2.5 microgram iloprost. 
 
This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver 
the pre-set dose of 2.5 or 5 microgram iloprost.  
For the 2.5 microgram dose of Ventavis 10 microgram/ml the medication chamber with the red 
coloured latch is used together with the red control disc.  
For the 5 microgram dose of Ventavis 10 microgram/ml the medication chamber with the purple 
coloured latch is used together with the purple control disc. 
 



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For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Ventavis 
10 microgram/ml, with two coloured rings (white - yellow), is transferred into the medication 
chamber immediately before use. 

 

Drug 
product 

Ampoule  
coloured ring Dosage 

I-Neb AAD Estimated 
inhalation 
time Medication 

chamber latch 
Control 
disc 

Ventavis 
10 mcg/ml 

1 ml ampoule 
white - yellow ring 

2.5 mcg red red 3.2 min 

5 mcg purple purple 6.5 min 
 
Ventavis 20 microgram/ml nebuliser solution 
 
Only patients who are maintained at the 5 microgram dose and who have repeatedly experienced 
extended inhalation times with Ventavis 10 microgram/ml, which could result in incomplete 
inhalation, may be considered suitable for switching to Ventavis 20 microgram/ml. 
 
Close supervision by the treating physician is necessary if switching from Ventavis 10 microgram/ml 
to Ventavis 20 microgram/ml to control the acute tolerance relating to faster delivery rate of iloprost 
with the double concentration. 
 
This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver 
the pre-set dose of 5 microgram iloprost.  
For the 5 microgram dose of Ventavis 20 microgram/ml the medication chamber with the gold 
coloured latch is used together with the gold control disc. 
 
For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Ventavis 
20 microgram/ml with two coloured rings (yellow - red), is transferred into the medication chamber 
immediately before use. 
 

Drug product Ampoule  coloured rings Dosage 
I-Neb AAD 

Medication 
chamber latch Control disc 

Ventavis 
20 mcg/ml 

1 ml ampoule 
yellow - red ring 5 mcg golden  golden  

 
• Venta-Neb 
 
Venta-Neb, a portable ultrasonic battery-powered nebuliser, has been shown to be suitable for the 
administration of Ventavis 10 microgram/ml nebuliser solution (2 ml ampoule). The measured 
MMAD of the aerosol droplets was 2.6 micrometres.  
 
At initiation of Ventavis treatment with Venta-Neb the first inhaled dose should be 2.5 microgram 
iloprost as delivered at the mouthpiece of the nebuliser using 2 ml ampoule of Ventavis 
10 microgram/ml. If this dose is well tolerated, dosing should be increased to 5 microgram iloprost 
using 2 ml ampoule of Ventavis 10 microgram/ml and maintained at that dose. In case of poor 
tolerability of the 5 microgram dose, the dose should be reduced to 2.5 microgram iloprost. 
 
For each inhalation session with the Venta-Neb, the content of one 2 ml ampoule of Ventavis 
10 microgram/ml with two coloured rings (white – pink) is transferred into the nebuliser medication 
chamber immediately before use.  



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Two programmes can be operated: 
P1 Programme 1: 5 microgram active substance on the mouth piece 25 inhalation cycles. 
P2 Programme 2: 2.5 microgram active substance on the mouth piece 10 inhalation cycles. 
The selection of the pre-set programme is made by the physician. 
 
Venta-Neb prompts the patient to inhale by an optical and an acoustic signal. It stops after the pre-set 
dose has been administered. 
To obtain the optimal droplet size for the administration of Ventavis 10 microgram/ml nebuliser 
solution the green baffle plate should be used. For details refer to the instruction manual of the Venta-
Neb nebuliser. 
 

Drug product 
Ampoule 

coloured ring 
Dose of iloprost at 
mouthpiece 

Estimated inhalation 
time 

Ventavis 10 mcg/ml 2 ml ampoule white - pink ring 
2.5 mcg 
5 mcg 

4 min 
8 min 

 
Other nebulising systems 
 
The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems, 
which provide different nebulisation characteristics of iloprost solution, have not been established. 
 
4.3 Contraindications 
 
− Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
− Conditions where the effects of Ventavis on platelets might increase the risk of haemorrhage 

(e.g. active peptic ulcers, trauma, intracranial haemorrhage). 
− Severe coronary heart disease or unstable angina. 
− Myocardial infarction within the last six months.  
− Decompensated cardiac failure if not under close medical supervision. 
− Severe arrhythmias. 
− Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last 3 months. 
− Pulmonary hypertension due to venous occlusive disease. 
− Congenital or acquired valvular defects with clinically relevant myocardial function disorders 

not related to pulmonary hypertension. 
 
4.4 Special warnings and precautions for use 
 
The use of Ventavis is not recommended in patients with unstable pulmonary hypertension, with 
advanced right heart failure. In case of deterioration or worsening of right heart failure transfer to 
other medicinal products should be considered. 
 
Hypotension 
 
Blood pressure should be checked while initiating Ventavis. In patients with low systemic blood 
pressure and in patients with postural hypotension or receiving medicinal products known to reduce 
blood pressure levels, care should be taken to avoid further hypotension. Ventavis should not be 
initiated in patients with systolic blood pressure less than 85 mmHg.  
Physicians should be alerted to the presence of concomitant conditions or medicinal products that 
might increase the risk of hypotension and syncope (see section 4.5). 
 



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Syncope 
 
The pulmonary vasodilatory effect of inhaled iloprost is of short duration (one to two hours). 
Syncope is a common symptom of the disease itself and can also occur under therapy. Patients who 
experience syncope in association with pulmonary hypertension should avoid any exceptional 
straining, for example during physical exertion. Before physical exertion it might be useful to inhale. 
The increased occurrence of syncope can reflect therapeutic gaps, insufficient effectiveness and/or 
deterioration of the disease. The need to adapt and/or change the therapy should be considered (see 
section 4.8). 
 
Patients with diseases of the respiratory tract 
 
Ventavis inhalation might entail the risk of inducing bronchospasm, especially in patients with 
bronchial hyperactivity (see section 4.8). Moreover, the benefit of Ventavis has not been established 
in patients with concomitant Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. 
Patients with concomitant acute pulmonary infections, COPD and severe asthma should be carefully 
monitored.  
 
Pulmonary veno-occlusive disease 
 
Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary 
veno-occlusive disease. Should signs of pulmonary oedema occur, the possibility of associated 
pulmonary veno-occlusive disease should be considered and treatment with Ventavis should be 
discontinued. 
 
Interruption of therapy 
 
In case of interruption of Ventavis therapy, the risk of rebound effect is not formally excluded. 
Careful monitoring of the patient should be performed when inhaled iloprost therapy is stopped and 
an alternative treatment should be considered in critically ill patients. 
 
Renal or hepatic impairment 
 
Data with intravenously administered iloprost indicated that the elimination is reduced in patients 
with hepatic dysfunction and in patients with renal failure requiring dialysis (see section 5.2). A 
cautious initial dose titration using dosing intervals of 3-4 hours is recommended (see section 4.2). 
 
Serum glucose levels 
 
Prolonged oral treatment with iloprost clathrate in dogs up to one year was associated with slightly 
increased fasted serum glucose levels. It cannot be excluded that this is also relevant to humans on 
prolonged Ventavis therapy.  
 
Undesirable exposure to Ventavis 
 
To minimise accidental exposure, it is recommended to use Ventavis with nebulisers with inhalation-
triggered systems (such as Breelib or I-Neb), and to keep the room well ventilated. 
Newborns, infants and pregnant women should not be subjected to Ventavis in the room air. 
 
Skin and eye contact, oral ingestion 
 
Ventavis nebuliser solution should not come into contact with skin and eyes; oral ingestion of 
Ventavis solution should be avoided. During nebulisation sessions a facial mask must be avoided and 
only a mouthpiece should be used. 
 



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Ventavis contains ethanol 
 
This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
 
Switching to the Breelib nebuliser 
 
Limited data are available on the use of the Breelib nebuliser. For patients being switched from an 
alternative device to the Breelib nebuliser the first inhalation should be made with Ventavis 
10 microgram/ml (1ml ampoule) delivering 2.5 microgram iloprost at the mouthpiece and under close 
medical supervision to ensure that the faster inhalation provided by Breelib is well tolerated. First 
dosing with 2.5 microgram should be done even if patients had already been stable on 5 microgram 
inhaled with an alternative device (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk 
of hypotension (see section 4.4). Caution is recommended in case of co-administration of Ventavis 
with other antihypertensive or vasodilatating agents as dose adjustment might be required. 
 
Since iloprost inhibits platelet function its use with the following substances may enhance iloprost-
mediated platelet inhibition, thereby increasing the risk of bleeding: 
• anticoagulants, such as 

- heparin, 
- oral anticoagulants (either coumarin-type or direct), 

• or other inhibitors of platelet aggregation, such as 
- acetylsalicylic acid, 
- non-steroidal anti-inflammatory medicinal products, 
- non-selective phosphodiesterase inhibitors like pentoxifylline, 
- selective phosphodiesterase 3 (PDE3) inhibitors like cilostazol or anagrelide, 
- ticlopidine, 
- clopidogrel, 
- glycoprotein IIb/IIIa antagonists, like 

o abciximab, 
o eptifibatide, 
o tirofiban, 

- defibrotide. 
 

A careful monitoring of the patients taking anticoagulants or other inhibitors of platelet aggregation 
according to common medical practice is recommended.  

 
Intravenous infusion of iloprost has no effect either on the pharmacokinetics of multiple oral doses of 
digoxin or on the pharmacokinetics of co-administered tissue plasminogen activator (t-PA) in patients. 
Although, clinical studies have not been conducted, in vitro studies investigating the inhibitory 
potential of iloprost on the activity of cytochrome P450 enzymes revealed that no relevant inhibition 
of drug metabolism via these enzymes by iloprost is to be expected.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential  
 
Women of childbearing potential should use effective contraceptive measures during treatment with 
Ventavis. 
 



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Pregnancy 
 
Women with pulmonary hypertension (PH) should avoid pregnancy as it may lead to life-threatening 
exacerbation of the disease. 
Animal studies have shown reproductive effects (see section 5.3).  
There is a limited amount of data from the use of iloprost in pregnant women. If a pregnancy occurs, 
taking into account the potential maternal benefit, the use of Ventavis during pregnancy may be 
considered, only following careful benefit-risk evaluation, in those women who choose to continue 
their pregnancy, despite the known risks of pulmonary hypertension during pregnancy. 
 
Breast-feeding 
 
It is not known whether iloprost/metabolites are excreted in human breast milk. Very low levels of 
iloprost into milk were observed in rats (see section 5.3). A potential risk to the breast-feeding child 
cannot be excluded and it is preferable to avoid breast-feeding during Ventavis therapy.  
 
Fertility 
 
Animal studies have not shown harmful effect of iloprost on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Ventavis has major influence on the ability to drive and use machines for patients experiencing 
hypotensive symptoms such as dizziness. 
Care should be exercised during initiation of therapy until any effects on the individual have been 
determined.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In addition to local effects resulting from administration of iloprost by inhalation such as cough, 
adverse reactions with iloprost are related to the pharmacological properties of prostacyclins. 
 
The most frequently observed adverse reactions (≥ 20 %) in clinical trials include vasodilatation 
(including hypotension), headache and cough. The most serious adverse reactions were hypotension, 
bleeding events, and bronchospasm. 
 
Tabulated list of adverse reactions 
 
The adverse reactions reported below are based on pooled clinical trial data from phase II and III 
clinical trials involving 131 patients taking the medicinal product and on data from post-marketing 
surveillance. The frequencies of adverse reactions are defined as very common (≥1/10) and common 
(≥1/100 to <1/10). The adverse reactions identified only during post-marketing surveillance, and for 
which a frequency could not be estimated from clinical trial data, are listed under "Frequency not 
known". 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.  
 



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System organ class 
(MedDRA) 
 

Very common 
(≥1/10) 

Common 
(≥1/100 to <1/10) 

Not known (cannot 
be estimated from 
the available data) 

Blood and lymphatic system 
disorders 

Bleeding events*§  Thrombocytopenia 

Immune system disorders   Hypersensitivity 

Nervous system disorders Headache Dizziness   

Cardiac disorders  Tachycardia 
Palpitations 

 

Vascular disorders Vasodilatation 
Flushing 

Syncope§ (see 
section 4.4)  
Hypotension* 

 

Respiratory, thoracic and 
mediastinal disorders 

Chest discomfort / 
chest pain 
Cough  

Dyspnoea 
Pharyngolaryngeal 
pain  
Throat irritation  

Bronchospasm* (see 
section 4.4) / 
Wheezing 

Gastrointestinal disorders Nausea Diarrhoea 
Vomiting 
Mouth and tongue 
irritation including 
pain 

Dysgeusia 
 

Skin and subcutaneous 
tissue disorders 

 Rash  

Musculoskeletal and 
connective tissue disorders 
 

Pain in jaw/trismus   

General disorders and 
administration site condition 

Peripheral oedema§   

* Life-threatening and/or fatal cases have been reported. 
§ see section “Description of selected adverse reactions” 
 
Description of selected adverse reactions 
 
Bleeding events (mostly epistaxis and haemoptysis) were very common as expected in this patient 
population with a high proportion of patients taking anticoagulant co-medication. The risk of bleeding 
may be increased in patients when potential inhibitors of platelet aggregation or anticoagulants are 
given concomitantly (see section 4.5). Fatal cases included cerebral and intracranial haemorrhage. 
 
Syncope is a common symptom of the disease itself, but can also occur under therapy. The increased 
occurrence of syncope can be related to the deterioration of the disease or insufficient effectiveness of 
the product (see section 4.4). 
 
In clinical trials peripheral oedema was reported in 12.2% of patients on iloprost and 16.2% of 
patients on placebo. Peripheral oedema is a very common symptom of the disease itself, but can also 
occur under therapy. The occurrence of peripheral oedema can be related to the deterioration of the 
disease or insufficient effectiveness of the product. 
 



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Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
 
Cases of overdose were reported. Symptoms of overdoses are mainly related to the vasodilatory effect 
of iloprost. Frequently observed symptoms following overdose are dizziness, headache, flushing, 
nausea, jaw pain or back pain. Hypotension, an increase of blood pressure, bradycardia or 
tachycardia, vomiting, diarrhoea and limb pain might also be possible. 
 
Management 
 
A specific antidote is not known. Interruption of the inhalation session, monitoring and symptomatic 
measures are recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antithrombotic agents, platelet aggregation inhibitors excluding heparin, 
ATC code: B01AC11 
 
Iloprost, the active substance of Ventavis, is a synthetic prostacyclin analogue. The following 
pharmacological effects have been observed in vitro: 
• Inhibition of platelet aggregation, platelet adhesion and release reaction 
• Dilatation of arterioles and venules 
• Increase of capillary density and reduction of increased vascular permeability caused by 

mediators such as serotonin or histamine in the microcirculation  
• Stimulation of endogenous fibrinolytic potential 
 
The pharmacological effects after inhalation of Ventavis are: 
 
Direct vasodilatation of the pulmonary arterial bed occur with consecutive significant improvement of 
pulmonary artery pressure, pulmonary vascular resistance and cardiac output as well as mixed venous 
oxygen saturation.  
 
In a small, randomised, 12-week double-blinded, placebo-controlled study (the STEP trial), 
34 patients treated with bosentan 125 mg twice per day for at least 16 weeks who were in stable 
haemodynamic conditions before enrolment, tolerated the addition of inhaled iloprost at the 
concentration of 10 microgram/ml (up to 5 microgram 6 to 9 times per day during waking hours). The 
mean daily inhaled dose was 27 microgram and the mean number of inhalations per day was 5.6. The 
acute adverse effects in patients receiving concomitant bosentan and iloprost were consistent with 
those observed in the larger experience of the phase 3 study in patients receiving only iloprost. No 
reliable conclusion could be drawn on efficacy of the association as the sample size was limited and 
the study was of short duration. 
 
No clinical trial data are available comparing directly in intra-patient observations the acute 
haemodynamic response after intravenous to that after inhaled iloprost. The haemodynamics observed 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


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suggest an acute response with preferential effect of inhaled treatment on the pulmonary vessels. The 
pulmonary vasodilatory effect of each single inhalation levels off within one to two hours. 
 
However, the predictive value of these acute haemodynamic data are considered to be of limited value 
as acute response does not in all cases correlate with long-term benefit of treatment with inhaled 
iloprost. 
 
Efficacy in adult patients with pulmonary hypertension 
 
A randomised, double-blind, multi-centre, placebo-controlled phase III trial (study RRA02997) has 
been conducted in 203 adult patients (inhaled iloprost at the concentration of 10 microgram/ml: 
N=101; placebo n=102) with stable pulmonary hypertension. Inhaled iloprost (or placebo) was added 
to patients' current therapy, which could include a combination of anticoagulants, vasodilators (e.g. 
calcium channel blockers), diuretics, oxygen, and digitalis, but not PGI2 (prostacyclin or its 
analogues). 108 of the patients included were diagnosed with primary pulmonary hypertension, 95 
were diagnosed with secondary pulmonary hypertension of which 56 were associated with chronic 
thromboembolic disease, 34 with connective tissue disease (including CREST and scleroderma) and 4 
were considered appetite suppressant medicinal product related. The baseline 6-minute walk test 
values reflected a moderate exercise limitation: in the iloprost group the mean was 332 metres 
(median value: 340 metres) and in the placebo group the mean was 315 metres (median value: 
321 metres). In the iloprost group, the median daily inhaled dose was 30 microgram (range 12.5 to 
45 microgram/day). The primary efficacy endpoint defined for this study, was a combined response 
criterion consisting of improvement in exercise capacity (6-minute walk test) at 12 weeks by at least 
10% versus baseline, and improvement by at least one NYHA class at 12 weeks versus baseline, and 
no deterioration of pulmonary hypertension or death at any time before 12 weeks. The rate of 
responders to iloprost was 16.8% (17/101) and the rate of responders in the placebo group was 4.9% 
(5/102) (p=0.007).  
 
In the iloprost group, the mean change from baseline after 12 weeks of treatment in the 6-minute 
walking distance was an increase of 22 metres (-3.3 metres in the placebo group, no data imputation 
for death or missing values).  
 
In the iloprost group the NYHA class was improved in 26% of patients (placebo: 15%) (p = 0.032), 
unchanged in 67.7% of patients (placebo: 76%) and deteriorated in 6.3% of patients (placebo: 9%). 
Invasive haemodynamic parameters were assessed at baseline and after 12 weeks treatment. 
 
A subgroup analysis showed that no treatment effect was observed as compared to placebo on the 
6-minute walk test in the subgroup of patients with secondary pulmonary hypertension.  
A mean increase in the 6-minute walk test of 44.7 metres from a baseline mean value of 329 metres 
vs. a change of -7.4 metres from a baseline mean value of 324 metres in the placebo group (no data 
imputation for death or missing values) was observed in the subgroup of 49 patients with primary 
pulmonary hypertension receiving treatment of inhaled iloprost for 12 weeks (46 patients in the 
placebo group).  
 
Paediatric population 
 
No study has been performed with Ventavis in children with pulmonary hypertension. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
When iloprost at the concentration of 10 microgram/ml is administered via inhalation in patients with 
pulmonary hypertension or healthy volunteers (iloprost dose at the mouthpiece: 5 microgram: 
inhalation time in between 4.6 – 10.6 min), mean peak serum concentrations of about 100 to 
200 picogram/ml were observed at the end of inhalation session. These concentrations decline with 



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half-lives between approximately 5 and 25 minutes. Within 30 minutes to 2 hours after the end of 
inhalation, iloprost is not detectable in the central compartment (limit of quantification 
25 picogram/ml). 
 
Distribution  
 
No studies performed following inhalation. 
 
Following intravenous infusion, the apparent steady-state volume of distribution was 0.6 to 0.8 l/kg in 
healthy subjects. Total plasma protein binding of iloprost is concentration-independent in the range of 
30 to 3,000 picogram/ml and amounts to approximately 60%, of which 75% is due to albumin 
binding. 
 
Biotransformation 
 
No studies to investigate the metabolism of iloprost were performed following inhalation of Ventavis. 
 
After intravenous administration, iloprost is extensively metabolised via ß-oxidation of the carboxyl 
side chain. No unchanged substance is eliminated. The main metabolite is tetranor-iloprost, which is 
found in the urine in free and conjugated form. Tetranor-iloprost is pharmacologically inactive as 
shown in animal experiments. Results of in vitro studies reveal that CYP 450-dependent metabolism 
plays only a minor role in the biotransformation of iloprost. Further in vitro studies suggest that 
metabolism of iloprost in the lungs is similar after intravenous administration or inhalation. 
 
Elimination 
 
No studies performed following inhalation. 
 
In subjects with normal renal and hepatic function, the disposition of iloprost following intravenous 
infusion is characterised in most cases by a two-phase profile with mean half-lives of 3 to 5 minutes 
and 15 to 30 minutes. The total clearance of iloprost is about 20 ml/kg/min, which indicates 
extrahepatic contribution to the metabolism of iloprost. 
 
A mass-balance study was done using 3H-iloprost in healthy subjects. Following intravenous infusion, 
the recovery of total radioactivity is 81 %, and the respective recoveries in urine and faeces are 68% 
and 12%. The metabolites are eliminated from plasma and urine in 2 phases, for which half-lives of 
about 2 and 5 hours (plasma) and 2 and 18 hours (urine) have been calculated. 
 
Pharmacokinetics after use with different nebulisers 
 
Breelib nebuliser: 
Pharmacokinetics of iloprost were investigated in a randomised, crossover study with 27 patients, 
stable on Ventavis 10 microgram/ml inhaled with I-Neb, following inhalation of single doses of 2.5 or 
5 microgram iloprost using the Breelib or the I-Neb AAD nebuliser. Following inhalation of these 
doses with the Breelib the maximum plasma concentrations (Cmax) and systemic exposures (AUC 
(0-tlast)) increased dose-proportionally. 
Cmax and AUC (0–tlast) after inhalation of 5 microgram iloprost administered as Ventavis 
20 microgram/ml using the Breelib were 77% and 42%, respectively higher compared to inhalation of 
the same dose using Ventavis 10 microgram/ml and the I-Neb AAD system. Cmax and AUC (0–tlast) of 
iloprost after inhalation with Breelib were, however, still in the range of values observed with 
Ventavis 10 microgram/ml using other inhalers across different studies. 
 
I-Neb AAD nebuliser: 
Pharmacokinetics under the specific study conditions of extended inhalation time, were investigated 
in a randomised, crossover study with 19 healthy adult men following inhalation of single doses of 
Ventavis 10 microgram/ml and Ventavis 20 microgram/ml (dose of 5 microgram iloprost at the 



14 

mouthpiece) using the I-Neb. Comparable systemic exposures (AUC (0–tlast)) and approximately 30% 
higher maximum serum concentrations (Cmax) were found following inhalation of Ventavis 
20 microgram/ml compared to Ventavis 10 microgram/ml which was in line with the observed shorter 
inhalation time using Ventavis 20 microgram/ml. 
 
Other special populations 
 
Renal impairment 
In a study with intravenous infusion of iloprost, patients with end-stage renal failure undergoing 
intermittent dialysis treatment are shown to have a significantly lower clearance 
(mean CL = 5 ± 2 ml/minute/kg) than that observed in patients with renal failure not undergoing 
intermittent dialysis treatment (mean CL = 18 ± 2 ml/minute/kg). 
 
Hepatic impairment 
Because iloprost is extensively metabolised by the liver, the plasma levels of the active substance are 
influenced by changes in hepatic function. In an intravenous study, results were obtained involving 
8 patients suffering from liver cirrhosis. The mean clearance of iloprost is estimated to be 
10 ml/minute/kg. 
 
Gender 
Gender is not of clinical relevance to the pharmacokinetics of iloprost. 
 
Elderly 
Pharmacokinetics in elderly patients have not been investigated. 
 
5.3 Preclinical safety data 
 
Systemic toxicity 
 
In acute toxicity studies, single intravenous and oral doses of iloprost caused severe symptoms of 
intoxication or death (intravenous) at doses about two orders of magnitude above the intravenous 
therapeutic dose. Considering the high pharmacological potency of iloprost and the absolute doses 
required for therapeutic purposes the results obtained in acute toxicity studies do not indicate a risk of 
acute adverse effects in humans. As expected for a prostacyclin, iloprost produced haemodynamic 
effects (vasodilatation, reddening of skin, hypotension, inhibition of platelet function, respiratory 
distress) and general signs of intoxication such as apathy, gait disturbances, and postural changes. 
 
Continuous intravenous/subcutaneous infusion of iloprost up to 26 weeks in rodents and non-rodents 
did not cause any organ toxicity at dose levels which exceeded the human therapeutic systemic 
exposure between 14 and 47 times (based on plasma levels). Only expected pharmacological effects 
like hypotension, reddening of skin, dyspnoea, increased intestinal motility were observed. 
 
In a chronic inhalation study in rats over 26 weeks, the highest achievable dose of 
48.7 microgram/kg/day was identified as ‘no observed adverse effect level’ (NOAEL). Systemic 
exposures exceeded human therapeutic exposures after inhalation by factors of more than 10 (Cmax, 
cumulative AUC). 
 
Genotoxic potential, tumourigenicity 
 
In vitro (bacterial, mammalian cells, human lymphocytes) and in vivo studies (micronucleus test) for 
genotoxic effects have not produced any evidence for a mutagenic potential. 
No tumourigenic potential of iloprost was observed in tumourigenicity studies in rats and mice. 
 



15 

Reproductive toxicology 
 
In embryo- and foetotoxicity studies in rats continuous intravenous administration of iloprost led to 
anomalies of single phalanges of the forepaws in a few foetuses/pups without dose dependence. 
 
These alterations are not considered as teratogenic effects, but are most likely related to iloprost 
induced growth retardation in late organogenesis due to haemodynamic alterations in the 
foetoplacental unit. No disturbance of postnatal development and reproductive performance was seen 
in the offspring that were raised, indicating that the observed retardation in rats was compensated 
during the postnatal development. In comparable embryotoxicity studies in rabbits and monkeys no 
such digit anomalies or other gross-structural anomalies were observed even after considerably higher 
dose levels which exceeded the human dose multiple times. 
In rats, passage of low levels of iloprost and/or metabolites into the milk was observed (less than 1% 
of iloprost dose given intravenously). No disturbance of post-natal development and reproductive 
performance was seen in animals exposed during lactation. 
 
Local tolerance, contact sensitising and antigenicity potential 
 
In inhalation studies in rats, the administration of an iloprost formulation with a concentration of 
20 microgram/ml up to 26 weeks did not cause any local irritation of the upper and lower respiratory 
tract. 
 
A dermal sensitisation (maximisation test) and an antigenicity study in guinea pigs showed no 
sensitising potential. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Trometamol 
Ethanol 96% 
Sodium chloride 
Hydrochloric acid (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
Ventavis 10 microgram/ml nebuliser solution 
4 years. 
 
Ventavis 20 microgram/ml nebuliser solution 
5 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 



16 

6.5 Nature and contents of container 
 
Ventavis 10 microgram/ml nebuliser solution 
 
• 1 ml ampoules, colourless, glass type I, containing 1 ml nebuliser solution, ring coded with two 

coloured rings (white - yellow). 
• 3 ml ampoules, colourless, glass type I, containing 2 ml nebuliser solution, ring coded with two 

coloured rings (white - pink). 
 
Ampoules with 1 ml nebuliser solution (for the use of Breelib or I-Neb AAD): 
 
Packages containing: 
• 30 ampoules 
• 42 ampoules. 
 
Multipacks containing: 
• 168 (4x42) ampoules 
• 168 (4x42) ampoules co-packed with Breelib consumables set (containing 1 mouthpiece and 1 

medication chamber). 
 
Ampoules with 2 ml nebuliser solution (for the use of Venta-Neb): 
 
Packages containing: 
• 30 ampoules  
• 90 ampoules 
• 100 ampoules  
• 300 ampoules. 
 
Multipacks containing: 
• 90 (3x30) ampoules 
• 300 (10x30) ampoules. 
 
 
Ventavis 20 microgram/ml nebuliser solution 
 
• 1 ml ampoules, colourless, glass type I, containing 1 ml nebuliser solution, ring coded with two 

coloured rings (yellow - red). 
 
Ampoules with 1 ml nebuliser solution (for the use of Breelib or I-Neb AAD): 
 
Packages containing: 
• 30 ampoules 
• 42 ampoules. 
 
Multipacks containing: 
• 168 (4x42) ampoules 
• 168 (4x42) ampoules co-packed with Breelib consumables set (containing 1 mouthpiece and 1 

medication chamber). 
 
Not all pack sizes may be marketed. 
 



17 

6.6 Special precautions for disposal and other handling 
 
For each inhalation session the content of one opened ampoule of Ventavis has to be transferred 
completely into the medication chamber immediately before use.  
 
After each inhalation session, any solution remaining in the nebuliser should be discarded. In 
addition, instructions for hygiene and cleaning of the nebulisers provided by the device manufacturers 
should be followed carefully. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Ventavis 10 microgram/ml nebuliser solution 
 
EU/1/03/255/001 
EU/1/03/255/002 
EU/1/03/255/003 
EU/1/03/255/004 
EU/1/03/255/005 
EU/1/03/255/006 
EU/1/03/255/007 
EU/1/03/255/008 
EU/1/03/255/011 
EU/1/03/255/013 
 
Ventavis 20 microgram/ml nebuliser solution 
 
EU/1/03/255/009 
EU/1/03/255/010 
EU/1/03/255/012 
EU/1/03/255/014 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 16 September 2003 
Date of latest renewal: 26 August 2013 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

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


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE  
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION  

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



19 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Berlimed S.A. 
Poligono Industrial Santa Rosa s/n 
28806 Alcalá de Henares 
Madrid 
Spain 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP)  
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



22 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
OUTER CARTON  
 
30 AMPOULES WITH 2 ML 
90 AMPOULES WITH 2 ML 
90 (3 x 30) AMPOULES WITH 2 ML 
100 AMPOULES WITH 2 ML 
300 AMPOULES WITH 2 ML 
300 (10 x 30) AMPOULES WITH 2 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 2 ml solution contains 20 microgram iloprost.  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
30 ampoules with 2 ml. 
90 ampoules with 2 ml. 
Multipack: 90 (3 x 30) ampoules with 2 ml. 
100 ampoules with 2 ml. 
300 ampoules with 2 ml. 
Multipack: 300 (10 x 30) ampoules with 2 ml. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Venta-Neb. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



23 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/001 [30 x 2 ml] 
EU/1/03/255/006 [90 x 2 ml] 
EU/1/03/255/007 [90 (3 x 30 ) x 2 ml] 
EU/1/03/255/002 [100 x 2 ml] 
EU/1/03/255/003 [300 x 2 ml] 
EU/1/03/255/008 [300 (10 x 30 ) x 2 ml] 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 10 microgram/ml; 2 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



24 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
INNER CARTON WITHOUT BLUE BOX 
 
PACK WITH 30 AMPOULES IN A CARTON WITH 90 (3 x 30) AMPOULES WITH 2 ML 
PACK WITH 30 AMPOULES IN A CARTON WITH 300 (10 x 30) AMPOULES WITH 2 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 2 ml solution contains 20 microgram iloprost. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
30 ampoules with 2 ml. Component of a multipack, can’t be sold separately. 
Part of a multipack containing 90 ampoules with 2 ml.  
Part of a multipack containing 300 ampoules with 2 ml.  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Venta-Neb. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



26 

 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/007 [90 (3 x 30) x 2 ml] 
EU/1/03/255/008 [300 (10 x 30) x 2 ml] 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 10 microgram/ml; 2 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Not applicable. 



27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
 
30 AMPOULES WITH 1 ML 
42 AMPOULES WITH 1 ML 
168 (4 x 42) AMPOULES WITH 1 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml, nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 10 microgram iloprost. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
30 ampoules with 1 ml.  
42 ampoules with 1 ml. 
Multipack: 168 (4 x 42) ampoules with 1 ml. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Breelib or the I-Neb. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



28 

8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/004 [30 x 1 ml] 
EU/1/03/255/011 [42 x 1 ml] 
EU/1/03/255/005 [168 (4 x 42) x 1 ml] 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 10 microgram/ml; 1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
 
168 (4 x 42) AMPOULES WITH 1 ML CO-PACKED WITH BREELIB CONSUMABLES SET 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml, nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 10 microgram iloprost. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
Multipack: 168 (4 x 42) ampoules with 1 ml co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Breelib. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



30 

9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/013 [168 (4 x 42) x 1 ml] co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 10 microgram/ml; 1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
INNER CARTON WITHOUT BLUE BOX 
 
PACK WITH 42 AMPOULES IN A CARTON WITH 168 (4 x 42) AMPOULES WITH 1 ML 
PACK WITH 42 AMPOULES IN A CARTON WITH 168 (4 x 42) AMPOULES WITH 1 ML 
CO-PACKED WITH BREELIB CONSUMABLES SET 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 10 microgram/ml, Nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 10 microgram iloprost. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
42 ampoules with 1 ml. Component of a multipack, can’t be sold separately. 
Part of a multipack containing 168 (4 x 42) ampoules with 1 ml.  
Part of a multipack containing 168 (4 x 42) ampoules with 1 ml co-packed with Breelib 
consumables set (containing 1 mouthpiece and 1 medication chamber). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



32 

8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/005 [168 (4 x 42) x 1 ml] 
EU/1/03/255/013 [168 (4 x 42) x 1 ml] co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 10 microgram/ml; 1 ml 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Not applicable. 



33 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
AMPOULE WITH 1 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ventavis 10 microgram/ml nebuliser solution 
Iloprost 
Inhalation use  
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot   
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
 



34 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
AMPOULE WITH 2 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ventavis 10 microgram/ml nebuliser solution 
Iloprost 
Inhalation use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2 ml 
 
 
6. OTHER 
 
 



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
OUTER CARTON 
 
30 AMPOULES WITH 1 ML 
42 AMPOULES WITH 1 ML 
168 (4 x 42) AMPOULES WITH 1 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 20 microgram/ml nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 20 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 20 microgram iloprost.  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
30 ampoules with 1 ml  
42 ampoules with 1 ml 
Multipack: 168 (4 x 42) ampoules with 1 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Breelib or the I-Neb. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



36 

8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/009 [30 x 1 ml] 
EU/1/03/255/012 [42 x 1 ml] 
EU/1/03/255/010 [168 (4 x 42) x 1 ml] 
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 20 microgram/ml; 1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
OUTER CARTON 
 
168 (4 x 42) AMPOULES WITH 1 ML CO-PACKED WITH BREELIB CONSUMABLES SET 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 20 microgram/ml nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 20 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 20 microgram iloprost.  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
Multipack: 168 (4 x 42) ampoules with 1 ml co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
For administration with the Breelib. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



38 

9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/014 [168 (4 x 42) x 1 ml] co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 20 microgram/ml; 1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



39 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
INNER CARTON WITHOUT BLUE BOX 
 
PACK WITH 42 AMPOULES IN A CARTON WITH 168 (4 x 42) AMPOULES WITH 1 ML 
PACK WITH 42 AMPOULES IN A CARTON WITH 168 (4 x 42) AMPOULES WITH 1 ML 
CO-PACKED WITH BREELIB CONSUMABLES SET 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ventavis 20 microgram/ml nebuliser solution 
Iloprost 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml solution contains 20 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml solution contains 20 microgram iloprost. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
trometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Nebuliser solution. 
42 ampoules with 1 ml. Component of a multipack, can’t be sold separately. 
Part of a multipack containing 168 (4 x 42) ampoules with 1 ml. 
Part of a multipack containing 168 (4 x 42) ampoules with 1 ml co-packed with Breelib 
consumables set (containing 1 mouthpiece and 1 medication chamber). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Inhalation use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



40 

8. EXPIRY DATE 
 
EXP  
 
 
9.  SPECIAL STORAGE CONDITIONS 
 
 
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 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/255/010 [168 (4 x 42) x 1 ml] 
EU/1/03/255/014 [168 (4 x 42) x 1 ml] co-packed with Breelib consumables set (containing 1 
mouthpiece and 1 medication chamber). 
 
 
13. BATCH NUMBER 
 
Lot  
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ventavis 20 microgram/ml; 1 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Not applicable. 



41 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
AMPOULE WITH 1 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ventavis 20 microgram/ml nebuliser solution 
Iloprost 
Inhalation use  
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 



42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



43 

Package leaflet: Information for the user 
 

Ventavis 10 microgram/ml nebuliser solution 
Iloprost 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 

 
What is in this leaflet 
 
1. What Ventavis is and what it is used for 
2. What you need to know before you use Ventavis 
3. How to use Ventavis 
4. Possible side effects 
5. How to store Ventavis 
6. Contents of the pack and other information 
 
 
1. What Ventavis is and what it is used for 
 
What Ventavis is 
The active substance of Ventavis is iloprost. It imitates a natural substance in the body called 
prostacyclin. Ventavis inhibits unwanted blocking or narrowing of blood vessels and allows more 
blood to flow through the vessels.  
 
What Ventavis is used for 
Ventavis is used to treat moderate cases of primary pulmonary hypertension (PPH) in adult patients. 
PPH is a category of pulmonary hypertension where the cause of the high blood pressure is not 
known.  
This is a condition where blood pressure is too high in the blood vessels between the heart and the 
lungs.  
Ventavis is used to improve exercise capacity (the ability to carry out physical activity) and 
symptoms. 
 
How Ventavis works 
Breathing in the mist carries Ventavis to the lungs, where it can work most effectively in the artery 
between heart and lungs. Improved blood flow leads to a better supply of oxygen to the body and 
reduced strain on the heart. 
 
 



44 

2. What you need to know before you use Ventavis 
 
Do not use Ventavis  
• if you are allergic to iloprost or any of the other ingredients of this medicine (listed in 

section 6), 
• if you are at risk of bleeding– for example, if you have an active ulcer of the stomach or of the 

first part of the small intestine (duodenal ulcers), if you have suffered a physical injury 
(trauma), if you are at risk of bleeding within the skull, 

• if you have a heart problem, such as 
- poor blood flow to the heart muscles (severe coronary heart disease or unstable angina). 

Symptoms can include chest pain, 
- a heart attack within the last six months, 
- a weak heart (decompensated cardiac failure) which is not under close medical 

observation, 
- severe unstable heartbeat, 
- a defect of the heart valves (inborn or acquired) that causes the heart to work 
 poorly (not related to pulmonary hypertension), 

• if you have had a stroke within the last 3 months, or any other occurrence that reduced the 
blood supply to the brain (e.g. transient ischaemic attack), 

• if your pulmonary hypertension is due to a blocked or narrowed vein (venous occlusive 
disease). 

 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before using Ventavis:  
• Inhaling Ventavis might trigger breathing difficulties (see section 4), especially in patients with 

bronchospasm (sudden constriction of the muscles in the walls of the small airways) and 
wheezing. Tell your doctor if you have a lung infection, severe asthma, or chronic lung 
disease (chronic obstructive pulmonary disease). Your doctor will monitor you closely. 

• Your blood pressure will be checked before treatment and if it is too low (less than 
85 mmHg for the upper value) then therapy with Ventavis should not be started. 

• In general, you will need to take special care to try and avoid effects of low blood pressure, 
such as fainting and dizziness:  
- Tell your doctor if you are taking any other medication because the combined effect with 

Ventavis may lower your blood pressure further (see below "Other medicines and 
Ventavis"). 

- Stand up slowly when you get out of chairs or bed.  
- If you tend to faint as soon as you get out of bed, it may be helpful to take your first dose 

of the day while you are still lying down. 
- If you tend to experience fainting episodes, avoid any exceptional straining, for example 

during physical exertion; it might be useful to inhale Ventavis before.  
• Fainting episodes may be due to the underlying disease. Tell your doctor if they get worse. 

He/she may consider adjusting your dose or changing your treatment. 
• If you suffer from a weak heart condition such as right heart failure, and feel that your 

disease is worsening, tell your doctor. Symptoms can include swelling of feet and ankles, 
shortness of breath, palpitations, urinating more frequently at night or oedema. Your doctor will 
consider changing your treatment. 

• If you experience difficulty breathing, cough up blood, and/or sweat excessively these may 
be signs that you have water in the lungs (lung oedema). Stop using Ventavis and tell your 
doctor immediately. He/she will look for the cause and take appropriate measures. 

• If you have liver problems or very severe kidney problems, requiring dialysis, tell your 
doctor. You may be gradually introduced to the prescribed dose or be prescribed a lower dose 
of Ventavis than for other patients (see section 3. "How to use Ventavis"). 

 



45 

Contact of Ventavis with skin or swallowing Ventavis 
• Do NOT let Ventavis solution come into contact with your skin or eyes.  

If it does, rinse the skin or your eyes immediately with plenty of water.  
• Do NOT drink or swallow Ventavis solution.  

If you swallow it accidentally, drink plenty of water and tell your doctor.  
 
Children and adolescents 
The safety and efficacy of Ventavis in children aged up to 18 years have not been established.  
 
Other medicines and Ventavis 
Tell your doctor or pharmacist if you are using, have recently used or might use any other 
medicines. Ventavis and certain other medicines may affect each other in the way they work in your 
body. 
 
Tell your doctor if you are taking: 
 
• Medicines used to treat high blood pressure or heart disease, such as  

- beta blockers, 
- nitro-vasodilators, 
- ACE inhibitors. 
Your blood pressure may drop much further. 
Your doctor may change the dosage. 
 

• Medicines that thin the blood or inhibit blood clotting, this includes 
- acetylsalicylic acid (ASA - a compound found in many medicines that lower fever and 

relieve pain), 
- heparin, 
- coumarin-type anticoagulants, such as warfarin or phenprocoumon, 
- non-steroidal anti-inflammatory drugs, 
- non-selective phosphodiesterase inhibitors, such as pentoxifylline, 
- selective phosphodiesterase 3 (PDE 3) inhibitors, such as cilostazol or anagrelide, 
- ticlopidine, 
- clopidogrel, 
- glycoprotein IIb/IIIa antagonists, such as 

o abciximab,  
o eptifibatide, 
o tirofiban, 

- defibrotide. 
Your doctor will monitor you carefully. 

 
Before taking any medicine ask your doctor or pharmacist, who has more information on medicines to 
be careful with or avoid when using Ventavis. 
 
Ventavis with food and drink 
Food or drink is not expected to affect Ventavis. However, you should avoid taking food or drink 
during inhalation. 
 
Pregnancy 
• If you suffer from pulmonary hypertension, avoid getting pregnant as pregnancy may lead to a 

worsening of your condition and may even endanger your life. 
• If you could get pregnant, use reliable contraception from the time you start treatment and during 

treatment. 
• If you are pregnant, think you might be or are planning to have a baby, tell your doctor 

straight away. Ventavis should only be used during pregnancy if your doctor decides that the 
potential benefit outweighs the potential risk to you and the foetus. 

 



46 

Breast-feeding 
It is not known whether Ventavis passes into human milk. A potential risk to the breast-feeding child 
cannot be excluded and it is preferable to avoid breast-feeding during Ventavis therapy. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Newborns, infants and pregnant women should not be in the same room while you are inhaling 
Ventavis. 
 
Driving and using machines 
Ventavis lowers blood pressure and may cause dizziness or light-headedness in some people.  
Do not drive or operate any tools or machines if you feel these effects.  
 
Ventavis contains ethanol 
Ventavis contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
 
 
3. How to use Ventavis 
 
Ventavis therapy should only be initiated by a physician experienced in treatment of pulmonary 
hypertension.  
 
How much to inhale and for how long 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The dose of Ventavis and the duration of treatment that is right for you depend on your individual 
condition. Your doctor will advise you. Do not change the recommended dose without consulting 
your doctor first. 
 
Different nebuliser devices can be used to administer Ventavis. Depending on the type of device used 
and dose prescribed, 1 ml or 2 ml of Ventavis 10 microgram/ml are appropriate. 
 
• Breelib nebuliser 
 
If you are starting Ventavis treatment or if you switch from an alternative device your first inhalation 
will be with Ventavis 10 microgram/ml (1 ml ampoule with white and yellow rings). If you tolerate 
this dose well, your next inhalation will be with Ventavis 20 microgram/ml (ampoule with yellow and 
red rings). You should continue on this dose. 
 
If you cannot tolerate inhalation of Ventavis 20 microgram/ml talk to your doctor who may decide 
that you should take Ventavis 10 microgram/ml (1 ml ampoule). 
 
Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation session 
with Breelib will usually last about 3 minutes. 
 
Your doctor will supervise your treatment when you start using the Breelib nebuliser to ensure that 
you tolerate dose and speed of inhalation well. 
 
• I-Neb AAD nebuliser (1 ml ampoule with white and yellow rings) 
 
In general, when starting Ventavis treatment the first inhaled dose should be 2.5 microgram iloprost as 
delivered at the mouthpiece. If you tolerate this dose well, your dose should be increased to 
5 microgram iloprost and you should continue on this dose. If you are unable to tolerate the 
5 microgram dose, the dose should be reduced to 2.5 microgram. 



47 

 
Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation session 
will usually last about 4 to 10 minutes with I-Neb AAD depending on the prescribed dose.  
 
• Venta-Neb nebuliser (2 ml ampoule with white and pink rings) 
 
In general, when starting Ventavis treatment the first inhaled dose should be 2.5 microgram iloprost as 
delivered at the mouthpiece. If you tolerate this dose well, your dose should be increased to 
5 microgram and you should continue on this dose. If you are unable to tolerate the 5 microgram dose, 
the dose should be reduced to 2.5 microgram. 
 
Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation session 
with Venta-Neb will usually last about 4 to 10 minutes depending on the prescribed dose.  
 
Depending on your individual needs, Ventavis can be used for long term treatment. 
 
If you have kidney or liver problems 
 
There is no need to alter the dose in patients with mild or moderate kidney problems (patients with a 
creatinine clearance > 30 ml/min).  
 
If you have very severe kidney problems and require dialysis or if you have liver problems, your 
doctor will introduce you to Ventavis gradually and possibly prescribe fewer daily inhalations. Start 
therapy by inhaling 2.5 microgram iloprost using 1 ml ampoule of Ventavis 10 microgram/ml (with 
white and yellow rings). Use dosing intervals of 3 – 4 hours (this corresponds to a maximum of 
6 administrations per day). Thereafter, your doctor may cautiously shorten the dosing intervals 
depending on how you tolerate the treatment. If your doctor decides to further increase the dose up to 
5 microgram, again dosing intervals of 3 - 4 hours should be chosen initially and shortened depending 
on how you tolerate the treatment. 
 
If you feel that the effect of Ventavis is too strong or too weak, talk to your doctor or pharmacist. 
Ask your doctor to have someone help you become thoroughly familiar with the use of the nebuliser. 
You should not switch to another nebuliser without consulting the doctor who is treating you. 
 
How to inhale 
 
For each inhalation session you should use a new ampoule of Ventavis. Just before you start to 
inhale, break the glass ampoule and pour the solution into the medication chamber following 
the instructions for use of the nebuliser. 
 
Follow carefully the instructions that come with the nebuliser especially the instructions on 
hygiene and cleaning of the nebuliser. 
 
Always take Ventavis exactly as your doctor has told you.  
• Ventavis 10 microgram/ml nebuliser solution is inhaled using the nebulisers your doctor 

prescribed (either the Breelib, the Venta-Neb or the I-Neb AAD system).  
• The nebuliser turns Ventavis solution into a mist which you breathe in through your 

mouth.  
• For the inhalation you should use a mouthpiece to prevent Ventavis coming into contact 

with your skin. Do not use a facial mask. 
• Follow carefully any instructions that come with the nebuliser. Check with your doctor or 

pharmacist if you are unsure. 
• Any Ventavis solution remaining in the nebuliser after inhalation must be thrown away (see 

section 5). 
 



48 

Room ventilation 
Be sure to ventilate or air the room in which you have taken your Ventavis treatment. Other people 
might accidentally be exposed to Ventavis through the room air. In particular, newborns, infants and 
pregnant women should not be in the same room while you are inhaling Ventavis. 
 
• Breelib 
 
Fill the medication chamber with Ventavis immediately before use. For filling please follow the 
instructions for use of the nebuliser. 
 

Device Drug product 
Dose of iloprost at 
mouthpiece 

Estimated 
inhalation time 

Breelib 
Ventavis 10 mcg/ml (1 ml 
ampoule with white and 
yellow rings) 

2.5 mcg 3 minutes 

 
• I-Neb AAD 
 
1. Just before you start to inhale, break the glass ampoule containing 1 ml solution, which has two 

coloured rings (white - yellow), and pour the complete contents into the nebuliser medication 
chamber.  

2. The pre-set dose provided by the I-Neb AAD system is controlled by the medication chamber in 
combination with a control disc. There are two different colour coded medication chambers. 
For each medication chamber there is a corresponding colour coded control disc: 
• For the 2.5 microgram dose the medication chamber with the red coloured latch is 

used together with the red control disc.  
• For the 5 microgram dose the medication chamber with the purple coloured latch is 

used together with the purple control disc. 
3. In order to ensure that you receive the prescribed dose, check the colour of the medication 

chamber and the colour of the control disc. They should both have the same colour, either red 
for the 2.5 microgram dose or purple for the 5 microgram dose. 

 

Device Dose of iloprost at mouthpiece Estimated inhalation time 

I-Neb AAD 2.5 microgram 5 microgram 
3.2 min 
6.5 min 

 
The table below provides a summary of the user instructions of the I-Neb: 
 

Drug product 
Ampoule  
coloured ring 

Dosage 
I-Neb AAD 

Medication 
chamber latch 

Control disc 

Ventavis 10 mcg/ml 
1 ml  ampoule 
white - yellow ring 

2.5 mcg red red 

5 mcg purple purple 

 



49 

• Venta-Neb 
 
1. Just before you start to inhale, break the glass ampoule containing 2 ml solution, which has two 

coloured rings (white-pink), and pour the complete contents into the nebuliser medication 
chamber.  

2. Two programmes can be operated: 
3. Your doctor will adjust Venta-Neb to the programme you need to receive the dose prescribed for 

you. 
• P1 Programme 1: 5 microgram active substance on the mouth piece 25 inhalation cycles. 
• P2 Programme 2: 2.5 microgram active substance on the mouth piece 10 inhalation 

cycles. 
4. You should use the green baffle plate to obtain the optimal droplet size for the administration of 

Ventavis.  
 

Device Dose of iloprost at mouthpiece Estimated inhalation time 

Venta-Neb 2.5 microgram 
5 microgram 

4 min 
8 min 

 
For further details please refer to the instruction manual of the nebuliser device or ask your doctor. 
 
If you use more Ventavis than you should 
Using more Ventavis than you should may lead to dizziness, headache, flushing (reddening of the 
face), nausea (feeling sick), jaw pain or back pain. 
You may also experience a decrease or an increase in blood pressure, bradycardia (reduced heart 
rate), tachycardia (increased heart rate), vomiting, diarrhoea or limb pain. If any of these happen when 
you have used more Ventavis than you should: 
• stop the inhalation session 
• talk to your doctor 
Your doctor will monitor you and treat any resulting symptoms. A specific antidote is not known. 
 
If you forget to use Ventavis 
Do not take a double dose to make up for a forgotten dose. Please ask your doctor what you should 
do. 
 
If you stop taking Ventavis 
If you stop or wish to stop treatment, discuss it with your doctor first. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
The following serious side effects may occur. In this case talk to your doctor immediately. 
 
Very common (may affect more than 1 in 10 people):  

• Bleeding events (mostly nosebleed (epistaxis) and coughing up blood (haemoptysis)) 
may very commonly occur, especially if you are also taking blood-thinning medicines 
(anticoagulants). The risk of bleeding may be increased in patients when inhibitors of 
platelet aggregation or anticoagulants are given at the same time (see also section 2). 
Very rarely, fatal cases including bleeding in the brain (cerebral and intracranial 
haemorrhage) have been reported. 

 



50 

Common (may affect up to 1 in 10 people):  
• Fainting (syncope) is a symptom of the illness itself but can also occur during treatment 

with Ventavis (see also section 2 "Warnings and precautions", for advice on what you 
can do to avoid this). 

• Low blood pressure (hypotension) 
 
Not known (cannot be estimated from the available data): 
• Bronchospasm (sudden constriction of the muscles in the walls of the small airways) and 

wheezing (see also section 2 “Warnings and precautions”) 
 
Below we list other possible side effects by how likely they are: 
 
Very common: may affect more than 1 in 10 people 
• widening of the blood vessels (vasodilatation). Symptoms can be flushing or reddening of the face. 
• chest discomfort / chest pain 
• coughing  
• headache 
• nausea 
• pain in jaw/spasm of the jaw muscles (trismus)  
• swelling of the limbs (peripheral oedema) 
 
Common: may affect up to 1 in 10 people 
• breathing difficulties (dyspnoea) 
• dizziness  
• vomiting 
• diarrhoea  
• pain when swallowing (pharyngolaryngeal irritation) 
• throat irritation 
• mouth and tongue irritation including pain 
• rash 
• fast heartbeat (tachycardia) 
• awareness of fast or hard heartbeat (palpitations) 
 
Not known: frequency cannot be estimated from the available data. 
• reduction in the number of blood platelets (thrombocytopenia) 
• hypersensitivity (i.e. allergy) 
• disturbed sense of taste (dysgeusia) 
 
Other possible effects 
• Swelling, mainly of the ankles and legs, due to fluid retention (peripheral oedema) is a very 

common symptom of the illness itself but can also occur during treatment with Ventavis. 
 
Reporting of side effects  
If you get any side effects talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix 
V. By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
5. How to store Ventavis 
 
Keep this medicine out of the sight and reach of children. 
Do not use this medicine after the expiry date which is stated on the carton and ampoule. 
This medicine does not require any special storage conditions. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc
https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


51 

Any Ventavis solution remaining in the nebuliser after inhalation must be thrown away. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information  
 
What Ventavis contains: 
 
• The active substance is iloprost. 
1 ml solution contains 10 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml contains 10 microgram iloprost. 
Each ampoule with 2 ml contains 20 microgram iloprost. 
 
• The other ingredients are trometamol, ethanol, sodium chloride, hydrochloric acid for pH 

adjustment, and water for injections. 
 
What Ventavis looks like and content of the pack: 
 
Ventavis is a clear, colourless nebuliser solution for inhalation with the Breelib, the I-Neb or the 
Venta-Neb nebuliser. 
Ventavis 10 microgram/ml is provided in colourless ampoules, containing either 1 ml or 2 ml 
nebuliser solution. 
 
Ventavis10 microgram/ml is available in the following packs: 
 
• 1 ml ampoules for use with Breelib or I-Neb nebulisers: 

- Pack containing 30 or 42 ampoules for use with the Breelib and I-Neb nebuliser. 
- Multipack containing 168 (4x42) ampoules for use with the Breelib and I-Neb nebuliser. 
- Multipack containing 168 (4x42) ampoules with Breelib consumables set (containing 1 

mouthpiece and 1 medication chamber). 
The ampoules containing 1 ml are marked with two coloured rings (white - yellow). 
 
• 2 ml ampoules for the use with Venta-Neb: 

- Pack containing 30, 90, 100 or 300 ampoules.  
- Multipack containing 90 (3x30) or 300 (10x30) ampoules.  

The ampoules containing 2 ml are marked with two coloured rings (white – pink).  
 
Not all pack-sizes may be marketed. 
 
Marketing Authorisation Holder: 
Bayer AG 
51368 Leverkusen 
Germany 
 
Manufacturer: 
Berlimed S.A. 
Poligono Industrial Santa Rosa s/n 
28806 Alcalá de Henares 
Madrid 
Spain 
 



52 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België / Belgique / Belgien 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Lietuva 
UAB Bayer 
Tel. +37 05 23 36 868 

България 
Байер България ЕООД 
Тел. +359 02-424 72 80 

Luxembourg / Luxemburg 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Česká republika 
Bayer s.r.o. 
Tel: +420 266 101 111 

Magyarország 
Bayer Hungária KFT 
Tel.:+36 14 87-41 00 

Danmark 
Bayer A/S 
Tlf: +45-45 23 50 00 

Malta 
Alfred Gera and Sons Ltd. 
Tel: +35 621 44 62 05 

Deutschland 
Bayer Vital GmbH 
Tel: +49 (0)214-30 513 48 

Nederland 
Bayer B.V. 
Tel: +31-(0)297-28 06 66 

Eesti 
Bayer OÜ 
Tel: +372 655 8565 

Norge 
Bayer AS 
Tlf. +47 23 13 05 00 

Ελλάδα 
Bayer Ελλάς ΑΒΕΕ 
Τηλ: +30 210 61 87 500 

Österreich 
Bayer Austria Ges. m. b. H. 
Tel: +43-(0)1-711 46-0 

España 
Bayer Hispania S.L. 
Tel: +34-93-495 65 00 

Polska 
Bayer Sp. z o.o. 
Tel.: +48 22 572 35 00 

France 
Bayer HealthCare 
Tél(N° vert): +33-(0)800 87 54 54 

Portugal 
Bayer Portugal, Lda. 
Tel: +351 21 416 42 00 

Hrvatska 
Bayer d.o.o. 
Tel: + 385-(0)1-6599 900 

România 
SC Bayer SRL 
Tel: +40 21 529 59 00 

Ireland 
Bayer Limited 
Tel: +353 1 2999313 

Slovenija 
Bayer d. o. o. 
Tel.: +386 (0)1 58 14 400 

Ísland 
Icepharma hf. 
Sími: +354 540 8000 

Slovenská republika 
Bayer, spol. s r.o. 
Tel: +421 2 59 21 31 11 

Italia 
Bayer S.p.A. 
Tel: +39 02 397 81 

Suomi/Finland 
Bayer Oy 
Puh/Tel: +358 20 785 21 

Κύπρος 
NOVAGEM Limited 
Τηλ: +357 22 48 38 58 

Sverige 
Bayer AB 
Tel: +46 (0) 8 580 223 00 

Latvija 
SIA Bayer 
Tel: +371 67 84 55 63 

United Kingdom 
Bayer plc 
Tel: +44 (0)118 206 3000 

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
------------------------------------------------------------------------------------------------------------------------------ 
 

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


53 

The following information is intended for healthcare professionals only: 
 
Instructions for use and handling 
 
Patients stabilised on one nebuliser should not switch to another nebuliser without close supervision 
by the treating doctor as different nebulisers have been shown to produce aerosols with slightly 
different physical characteristics and may have faster delivery of the solution (see section 5.2 of the 
Summary of Product Characteristics). 
 
To minimise accidental exposure, it is recommended to keep the room well ventilated. 
 
• Breelib 
 
When using the Breelib nebuliser please follow the instructions for use provided with the device. 
Fill the medication chamber with Ventavis immediately before use. 
 

Device Drug product Dose of iloprost at 
mouthpiece 

Estimated 
inhalation time 

Breelib  
Ventavis 10 mcg/ml (1 ml 
ampoule with white and 
yellow rings)  

2.5 mcg  3 minutes  

 
• I-Neb AAD  

 
The I-Neb AAD System is a portable, hand-held, vibrating mesh technology nebuliser system. This 
system generates droplets by ultrasound, which forces the solution through a mesh. The I-Neb AAD 
nebuliser has been shown to be suitable for the administration of Ventavis 10 microgram/ml (1 ml 
ampoule with white and yellow rings).  
The measured MMAD of the aerosol droplets was 2.1 micrometres.  
This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver 
the pre-set dose of 2.5 or 5 microgram iloprost.  
 
The dose delivered by the I-Neb AAD system is controlled by the medication chamber in combination 
with a control disc. Each medication chamber is colour coded and has a corresponding colour coded 
control disc. 
 
• For the 2.5 microgram dose the medication chamber with the red latch is used together with 

the red control disc.  
• For the 5 microgram dose the medication chamber with the purple coloured latch is used 

together with the purple control disc. 
 
For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Ventavis, with 
two coloured rings (white - yellow) is transferred into the medication chamber immediately before 
use.  
 

Device Dose of iloprost at mouthpiece Estimated inhalation time 

I-Neb AAD 2.5 microgram 5 microgram 
3.2 min 
6.5 min 

 



54 

The table below provides a summary of the user instructions of the I-Neb for Ventavis: 
 

Drug product Ampoule  coloured ring Dosage 
I-Neb AAD 

Medication 
chamber latch Control disc 

Ventavis 10 mcg/ml 1 ml ampoule white - yellow ring 
2.5 mcg red red 

5 mcg purple purple 
 
• Venta-Neb 
 
Venta-Neb, a portable ultrasonic battery-powered nebuliser, has also been shown to be suitable for the 
administration of Ventavis 10 microgram/ml. The measured MMAD of the aerosol droplets was 
2.6 micrometres. For each inhalation session, the content of one ampoule containing 2 ml of Ventavis 
10 microgram/ml nebuliser solution and marked with two coloured rings (white – pink) is transferred 
into the nebuliser medication chamber immediately before use.  
 
Two programmes can be operated: 
• P1 Programme 1: 5 microgram active substance on the mouth piece 25 inhalation cycles. 
• P2 Programme 2: 2.5 microgram active substance on the mouth piece 10 inhalation cycles. 
The selection of the pre-set programme is made by the doctor. 
 
Venta-Neb prompts the patient to inhale by an optical and an acoustic signal. It stops after the pre-set 
dose has been administered. To obtain the optimal droplet size for the administration of Ventavis the 
green baffle plate should be used. For details refer to the instruction manual of the Venta-Neb 
nebuliser. 
 

Device Dose of iloprost at mouthpiece Estimated inhalation time 

Venta-Neb 2.5 microgram 5 microgram 
4 min 
8 min 

 
The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems, 
which provide different nebulisation characteristics of iloprost solution, have not been established. 
 



55 

 
Package leaflet: Information for the user 

 
Ventavis 20 microgram/ml nebuliser solution 

Iloprost 
 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
 
1. What Ventavis is and what it is used for 
2. What you need to know before you use Ventavis 
3. How to use Ventavis 
4. Possible side effects 
5. How to store Ventavis 
6. Contents of the pack and other information 
 
 
1. What Ventavis is and what it is used for 
 
What Ventavis is 
The active substance of Ventavis is iloprost. It imitates a natural substance in the body called 
prostacyclin. Ventavis inhibits unwanted blocking or narrowing of blood vessels and allows more 
blood to flow through the vessels.  
 
What Ventavis is used for 
Ventavis is used to treat moderate cases of primary pulmonary hypertension (PPH) in adult patients. 
PPH is a category of pulmonary hypertension where the cause of the high blood pressure is not 
known.  
This is a condition where blood pressure is too high in the blood vessels between the heart and the 
lungs.  
Ventavis is used to improve exercise capacity (the ability to carry out physical activity) and 
symptoms. 
 
How Ventavis works 
Breathing in the mist carries Ventavis to the lungs, where it can work most effectively in the artery 
between heart and lungs. Improved blood flow leads to a better supply of oxygen to the body and 
reduced strain on the heart. 
 
 



56 

2. What you need to know before you use Ventavis 
 
Do not use Ventavis  
• if you are allergic to iloprost or any of the other ingredients of this medicine (listed in section 

6), 
• if you are at risk of bleeding– for example, if you have an active ulcer of the stomach or of the 

first part of the small intestine (duodenal ulcers), if you have suffered a physical injury 
(trauma), if you are at risk of bleeding within the skull, 

• if you have a heart problem, such as 
- poor blood flow to the heart muscles (severe coronary heart disease or unstable angina). 

Symptoms can include chest pain, 
- a heart attack within the last six months, 
- a weak heart (decompensated cardiac failure) which is not under close medical 

observation, 
- severe unstable heartbeat, 
- a defect of the heart valves (inborn or acquired) that causes the heart to work 

poorly (not related to pulmonary hypertension), 
• if you have had a stroke within the last 3 months, or any other occurrence that reduced the 

blood supply to the brain (e.g. transient ischaemic attack), 
• if your pulmonary hypertension is due to a blocked or narrowed vein (venous occlusive 

disease). 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before using Ventavis: 
 
• Inhaling Ventavis might trigger breathing difficulties (see section 4), especially in patients with 

bronchospasm (sudden constriction of the muscles in the walls of the small airways) and 
wheezing. Tell your doctor if you have a lung infection, severe asthma, or chronic lung 
disease (chronic obstructive pulmonary disease). Your doctor will monitor you closely. 

• Your blood pressure will be checked before treatment and if it is too low (less than 
85 mmHg for the upper value) then therapy with Ventavis should not be started. 

• In general, you will need to take special care to try and avoid effects of low blood pressure, 
such as fainting and dizziness: 
- Tell your doctor if you are taking any other medication because the combined effect with 

Ventavis may lower your blood pressure further (see below “Other medicines and 
Ventavis”). 

- Stand up slowly when you get out of chairs or bed.  
- If you tend to faint as soon as you get out of bed, it may be helpful to take your first dose 

of the day while you are still lying down. 
- If you tend to experience fainting episodes, avoid any exceptional straining, for example 

during physical exertion; it might be useful to inhale Ventavis before. 
• Fainting episodes may be due to the underlying disease. Tell your doctor if they get worse. 

He/she may consider adjusting your dose or changing your treatment. 
• If you suffer from a weak heart condition such as right heart failure, and feel that your 

disease is worsening, tell your doctor. Symptoms can include swelling of feet and ankles, 
shortness of breath, palpitations, urinating more frequently at night or oedema. Your doctor will 
consider changing your treatment. 

• If you experience difficulty breathing, cough up blood, and/or sweat excessively these may 
be signs that you have water in the lungs (lung oedema). Stop using Ventavis and tell your 
doctor immediately. He/she will look for the cause and take appropriate measures. 

• If you have liver problems or very severe kidney problems, requiring dialysis, tell your 
doctor. You may be gradually introduced to the prescribed dose or be prescribed a lower dose 
of Ventavis than for other patients (see section 3. “How to use Ventavis”). 

 



57 

Contact of Ventavis with skin or swallowing Ventavis 
• Do NOT let Ventavis solution come into contact with your skin or eyes.  

If it does, rinse the skin or your eyes immediately with plenty of water.  
• Do NOT drink or swallow Ventavis solution.  

If you swallow it accidentally, drink plenty of water and tell your doctor.  
 
Children and adolescents 
The safety and efficacy of Ventavis in children aged up to 18 years have not been established.  
 
Other medicines and Ventavis 
Tell your doctor or pharmacist if you are using, have recently used or might use any other 
medicines. Ventavis and certain other medicines may affect each other in the way they work in your 
body. 
 
Tell your doctor if you are taking: 
 
• Medicines used to treat high blood pressure or heart disease, such as 

- beta blockers, 
- nitro-vasodilators, 
- ACE inhibitors. 

Your blood pressure may drop much further. 
Your doctor may change the dosage. 
 

• Medicines that thin the blood or inhibit blood clotting, this includes 
- acetylsalicylic acid (ASA - a compound found in many medicines that lower fever and 

relieve pain), 
- heparin, 
- coumarin-type anticoagulants, such as warfarin or phenprocoumon, 
- non-steroidal anti-inflammatory drugs, 
- non-selective phosphodiesterase inhibitors, such as pentoxifylline, 
- selective phosphodiesterase 3 (PDE 3) inhibitors, such as cilostazol or anagrelide, 
- ticlopidine, 
- clopidogrel, 
- glycoprotein IIb/IIIa antagonists, such as 

o abciximab,  
o eptifibatide,  
o tirofiban, 

- defibrotide. 
Your doctor will monitor you carefully. 

 
Before taking any medicine ask your doctor or pharmacist, who has more information on medicines to 
be careful with or avoid when using Ventavis. 
 
Ventavis with food and drink 
Food or drink is not expected to affect Ventavis. However, you should avoid taking food or drink 
during inhalation. 
 
Pregnancy 
• If you suffer from pulmonary hypertension, avoid getting pregnant as pregnancy may lead to a 

worsening of your condition and may even endanger your life. 
•  If you could get pregnant, use reliable contraception from the time you start treatment and during 

treatment. 
• If you are pregnant, think you might be or are planning to have a baby, tell your doctor 

straight away. Ventavis should only be used during pregnancy if your doctor decides that the 
potential benefit outweighs the potential risk to you and the foetus. 

 



58 

Breast-feeding 
It is not known whether Ventavis passes into human milk. A potential risk to the breast-feeding child 
cannot be excluded and it is preferable to avoid breast-feeding during Ventavis therapy. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Newborns, infants and pregnant women should not be in the same room while you are inhaling 
Ventavis. 
 
Driving and using machines 
Ventavis lowers blood pressure and may cause dizziness or light-headedness in some people.  
Do not drive or operate any tools or machines if you feel these effects.  
 
Ventavis contains ethanol 
Ventavis contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
 
 
3. How to use Ventavis  
 
Ventavis therapy should only be initiated by a physician experienced in treatment of pulmonary 
hypertension.  
 
How much to inhale and for how long 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The dose of Ventavis and the duration of treatment that is right for you depend on your individual 
condition. Your doctor will advise you. Do not change the recommended dose without consulting 
your doctor first.  
 
Different nebuliser devices can be used to administer Ventavis 20µg/ml. 
 
• Breelib nebuliser 
 
If you are starting Ventavis treatment or if you switch from an alternative device your first inhalation 
will be with Ventavis 10 microgram/ml (1 ml ampoule with white and yellow rings). If you tolerate 
this dose well, your next inhalation will be with Ventavis 20 microgram/ml (ampoule with yellow and 
red rings). You should continue on this dose. 
 
If you cannot tolerate inhalation of Ventavis 20 microgram/ml talk to your doctor who may decide 
that you should take Ventavis 10 microgram/ml (1 ml ampoule). 
 
Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation session 
with Breelib will usually last about 3 minutes. 
 
Your doctor will supervise your treatment when you start using the Breelib nebuliser to ensure that 
you tolerate dose and speed of inhalation well. 
 
• I-Neb nebuliser  
 
As you repeatedly experience extended inhalation treatment times with Ventavis 10 microgram/ml (1 
ml ampoule with white and yellow rings), your doctor decided to switch to 
Ventavis 20 microgram/ml. 
 



59 

Ventavis 20 microgram/ml is double the concentration of Ventavis 10 microgram/ml. The active 
substance can be delivered more rapidly to your lungs. Your doctor will supervise your treatment if 
switching from Ventavis 10 microgram /ml to Ventavis 20 microgram/ml to monitor how well you 
tolerate the higher concentration. 
 
You should administer the dose 6 to 9 times per day according to individual needs and tolerability.  
 
Depending on your individual needs, Ventavis can be used for long term treatment. 
 
If you have kidney or liver problems 
 
There is no need to alter the dose in patients with mild or moderate kidney problems (patients with a 
creatinine clearance >30 ml/min).  
 
If you have very severe kidney problems and require dialysis or if you have liver problems, your 
doctor will introduce you to Ventavis gradually and possibly prescribe fewer daily inhalations. Start 
therapy by inhaling 2.5 microgram iloprost using Ventavis 10 micrograms/ml (1 ml ampoule with 
white and yellow rings). Use dosing intervals of 3 – 4 hours (this corresponds to a maximum of 
6 administrations per day). Thereafter, your doctor may cautiously shorten the dosing intervals 
depending on how you tolerate the treatment. If your doctor decides to further increase the dose up to 
5 microgram, again dosing intervals of 3 - 4 hours should be chosen initially and shortened depending 
on how you tolerate the treatment. 
 
If you feel that the effect of Ventavis is too strong or too weak, talk to your doctor or pharmacist. 
Ask your doctor to have someone help you become thoroughly familiar with the use of the nebuliser. 
You should not switch to another nebuliser without consulting the doctor who is treating you. 
 
How to inhale 
 
For each inhalation session you should use a new ampoule of Ventavis. Just before you start to 
inhale, break the glass ampoule and pour the solution into the medication chamber following 
the instructions for use of the nebuliser. 
 
Follow carefully the instructions that come with the nebuliser especially the instructions on 
hygiene and cleaning of the nebuliser. 
 
Always take Ventavis exactly as your doctor has told you.  
• Ventavis 20 microgram/ml nebuliser solution is inhaled using the nebulisers your doctor 

prescribed (either the Breelib or the I-Neb AAD nebuliser). 
• The nebuliser turns Ventavis solution into a mist which you breathe in through your 

mouth.  
• For the inhalation you should use a mouthpiece to prevent Ventavis coming into contact 

with your skin. Do not use a facial mask. 
• Follow carefully any instructions that come with the nebuliser. Check with your doctor or 

pharmacist if you are unsure. 
• Any Ventavis solution remaining in the nebuliser after inhalation must be thrown away (see 

section 5). 
 
Room ventilation 
Be sure to ventilate or air the room in which you have taken your Ventavis treatment. Other people 
might accidentally be exposed to Ventavis through the room air. In particular, newborns, infants and 
pregnant women should not be in the same room while you are inhaling Ventavis. 
 



60 

• Breelib 
 
Fill the medication chamber with Ventavis immediately before use. For filling please follow the 
instructions for use of the nebuliser. 
 

Device Drug product 
Dose of iloprost at 
mouthpiece 

Estimated 
inhalation time 

Breelib 
Ventavis 20 mcg/ml (1 ml 
ampoule with yellow and 
red rings) 

5 mcg 3 minutes 

 
• I-Neb AAD 

 
1. Just before you start to inhale, take the yellow-red colour coded ampoule of 

Ventavis 20 microgram/ml, break the glass ampoule and pour the complete contents of 1 ml into 
the nebuliser medication golden chamber. 

2. The pre-set dose provided by the I-Neb AAD nebuliser is controlled by the medication chamber in 
combination with a control disc. 

 For Ventavis 20 microgram/ml (5 microgram dose), the medication chamber with the golden 
coloured latch is used together with the golden control disc. 

3. To ensure that you receive the prescribed dose, check the colour of the medication chamber and 
the colour of the control disc. They should both have the same colour. 

 
Since the I-Neb AAD nebuliser can be used for Ventavis 10 microgram/ml and Ventavis 
20 microgram/ ml, the table below provides a summary of the user instructions of the I-Neb for the 2 
concentrations of Ventavis: 
 

Drug product Ampoule  coloured rings Dosage 
I-Neb AAD 

Medication  
chamber latch 

Control disc 

Ventavis 10 mcg/ml 1 ml ampoule white-yellow ring 

2.5 mcg 
 red red 

5 mcg 
 purple purple 

Ventavis 20 mcg/ml 1 ml ampoule 
yellow-red ring 5 mcg golden  golden  

 
For further details please refer to the instruction manual of the nebuliser device or ask your doctor. 
 
If you use more Ventavis than you should 
Using more Ventavis than you should may lead to dizziness, headache, flushing (reddening of the 
face), nausea (feeling sick), jaw pain or back pain. 
You may also experience a decrease or an increase in blood pressure, bradycardia (reduced heart 
rate), tachycardia (increased heart rate), vomiting, diarrhoea or limb pain. If any of these happen when 
you have used more Ventavis than you should: 
• stop the inhalation session  
• talk to your doctor  
Your doctor will monitor you and treat any resulting symptoms. A specific antidote is not known. 
 
If you forget to use Ventavis 
Do not take a double dose to make up for a forgotten dose. Please ask your doctor what you should 
do. 
 



61 

If you stop taking Ventavis 
If you stop or wish to stop treatment, discuss it with your doctor first. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
The following serious side effects may occur. In this case talk to your doctor immediately. 
 
Very common (may affect more than 1 in 10 people):  
• Bleeding events (mostly nosebleed (epistaxis) and coughing up blood (haemoptysis)) may very 

commonly occur, especially if you are also taking blood-thinning medicines (anticoagulants). 
The risk of bleeding may be increased in patients when inhibitors of platelet aggregation or 
anticoagulants are given at the same time (see also section 2). Very rarely, fatal cases including 
bleeding in the brain (cerebral and intracranial haemorrhage) have been reported. 

 
Common (may affect up to 1 in 10 people):  
• Fainting (syncope) is a symptom of the illness itself but can also occur during treatment 

with Ventavis (see also section 2 “Warnings and precautions”, for advice on what you 
can do to avoid this). 

• Low blood pressure (hypotension) 
 
Not known (cannot be estimated from the available data): 
• Bronchospasm (sudden constriction of the muscles in the walls of the small airways) and 

wheezing (see also section 2 “Warnings and precautions”) 
 
Below we list other possible side effects by how likely they are: 
 
Very common: may affect more than 1 in 10 people 
• widening of the blood vessels (vasodilatation). Symptoms can be flushing or reddening 

of the face. 
• chest discomfort / chest pain 
• coughing  
• headache 
• nausea 
• pain in jaw/spasm of the jaw muscles (trismus)  
• swelling of the limbs (peripheral oedema) 
 
Common: may affect up to 1 in 10 people 
• breathing difficulties (dyspnoea) 
• dizziness  
• vomiting 
• diarrhoea 
• pain when swallowing (pharyngolaryngeal irritation) 
• throat irritation 
• mouth and tongue irritation including pain 
• rash 
• fast heartbeat (tachycardia) 
• awareness of fast or hard heartbeat (palpitations) 
 



62 

Not known: frequency cannot be estimated from the available data. 
• reduction in the number of blood platelets (thrombocytopenia) 
• hypersensitivity (i.e. allergy) 
• disturbed sense of taste (dysgeusia)  
 
Other possible effects 
• Swelling, mainly of the ankles and legs, due to fluid retention (peripheral oedema) is a 

very common symptom of the illness itself but can also occur during treatment with 
Ventavis. 

 
Reporting of side effects  
If you get any side effects talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix 
V. By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
5. How to store Ventavis 
 
Keep this medicine out of the sight and reach of children. 
Do not use this medicine after the expiry date which is stated on the carton and ampoule. 
This medicine does not require any special storage conditions. 
 
Any Ventavis solution remaining in the nebuliser must be thrown away. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information  
 
What Ventavis contains: 
 
• The active substance is iloprost. 

1 ml solution contains 20 microgram iloprost (as iloprost trometamol).  
Each ampoule with 1 ml contains 20 microgram iloprost. 

 
• The other ingredients are trometamol, ethanol, sodium chloride, hydrochloric acid for pH 

adjustment, and water for injections. 
 
What Ventavis looks like and content of the pack: 
 
Ventavis is a clear, colourless to slightly yellowish nebuliser solution for inhalation with the Breelib 
or the I-Neb nebuliser.  
Ventavis 20 microgram/ml is provided in colourless ampoules, containing 1 ml nebuliser solution. 
 
Ventavis 20 microgram/ml is available in the following packs: 
- Pack containing 30 ampoules or 42 ampoules for use with the Breelib and I-Neb nebuliser.  
- Multipack containing 168 (4x42) ampoules for use with the Breelib and I-Neb nebuliser. 
- Multipack containing 168 (4x42) ampoules with Breelib consumables set (containing 1 

mouthpiece and 1 medication chamber). 
 
The ampoules containing 1 ml are marked with two coloured rings (yellow-red). 
 
Not all pack-sizes may be marketed. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc
https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


63 

Marketing Authorisation Holder: 
Bayer AG 
51368 Leverkusen 
Germany 
 
Manufacturer: 
Berlimed S.A. 
Polígono Industrial Santa Rosa s/n 
28806 Alcalá de Henares 
Madrid 
Spain 
 



64 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België / Belgique / Belgien 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Lietuva 
UAB Bayer 
Tel. +37 05 23 36 868 

България 
Байер България ЕООД 
Тел. +359 02-424 72 80 

Luxembourg / Luxemburg 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Česká republika 
Bayer s.r.o. 
Tel: +420 266 101 111 

Magyarország 
Bayer Hungária KFT 
Tel.:+36 14 87-41 00 

Danmark 
Bayer A/S 
Tlf: +45-45 23 50 00 

Malta 
Alfred Gera and Sons Ltd. 
Tel: +35 621 44 62 05 

Deutschland 
Bayer Vital GmbH 
Tel: +49 (0)214-30 513 48 

Nederland 
Bayer B.V. 
Tel: +31-(0)297-28 06 66 

Eesti 
Bayer OÜ 
Tel: +372 655 8565 

Norge 
Bayer AS 
Tlf. +47 23 13 05 00 

Ελλάδα 
Bayer Ελλάς ΑΒΕΕ 
Τηλ: +30 210 61 87 500 

Österreich 
Bayer Austria Ges. m. b. H. 
Tel: +43-(0)1-711 46-0 

España 
Bayer Hispania S.L. 
Tel: +34-93-495 65 00 

Polska 
Bayer Sp. z o.o. 
Tel.: +48 22 572 35 00 

France 
Bayer HealthCare 
Tél(N° vert): +33-(0)800 87 54 54 

Portugal 
Bayer Portugal, Lda. 
Tel: +351 21 416 42 00 

Hrvatska 
Bayer d.o.o. 
Tel: + 385-(0)1-6599 900 

România 
SC Bayer SRL 
Tel: +40 21 529 59 00 

Ireland 
Bayer Limited 
Tel: +353 1 2999313 

Slovenija 
Bayer d. o. o. 
Tel.: +386 (0)1 58 14 400 

Ísland 
Icepharma hf. 
Sími: +354 540 8000 

Slovenská republika 
Bayer, spol. s r.o. 
Tel: +421 2 59 21 31 11 

Italia 
Bayer S.p.A. 
Tel: +39 02 397 81 

Suomi/Finland 
Bayer Oy 
Puh/Tel: +358 20 785 21 

Κύπρος 
NOVAGEM Limited 
Τηλ: +357 22 48 38 58 

Sverige 
Bayer AB 
Tel: +46 (0) 8 580 223 00 

Latvija 
SIA Bayer 
Tel: +371 67 84 55 63 

United Kingdom 
Bayer plc 
Tel: +44 (0)118 206 3000 

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
------------------------------------------------------------------------------------------------------------------------------ 
 

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


65 

The following information is intended for healthcare professionals only: 
 
Instructions for use and handling 
 
Patients stabilised on one nebuliser should not switch to another nebuliser without close supervision 
by the treating doctor as different nebulisers have been shown to produce aerosols with slightly 
different physical characteristics and may have faster delivery of the solution (see section 5.2 of the 
Summary of Product Characteristics). 
 
To minimize accidental exposure, it is recommended to keep the room well ventilated. 
 
• Breelib 
 
When using the Breelib nebuliser please follow the instructions for use provided with the device. 
Fill the medication chamber with Ventavis immediately before use. 
 

Device  Drug product  
Dose of iloprost at  Estimated 

inhalation time  mouthpiece  
 

Breelib  
Ventavis 20 mcg/ml 
(1 ml ampoule with yellow 
and red rings)  

5 mcg  3 minutes  

 
• I-Neb AAD 
 
The I-Neb AAD System is a portable, hand-held, vibrating mesh technology nebuliser system. This 
system generates droplets by ultrasound, which is forcing the solution through a mesh. This nebuliser 
monitors the breathing pattern to determine the aerosol pulse time required to deliver the pre-set dose 
of 5 micrograms iloprost of the Ventavis 20 microgram/ml nebuliser solution (1 ml ampoule with 
yellow and red rings).  
The nebulising device delivers 5 microgram iloprost at the mouthpiece. The Mass Median 
Aerodynamic Diameter (MMAD) of the aerosol is between 1 and 5 micrometers. 
 
When using the I-Neb AAD system the following instructions need to be followed. 
The dose delivered by the I-Neb AAD system is controlled by the medication chamber in combination 
with a control disc. For each medication chamber there is a corresponding colour coded control disc. 
 
For each inhalation session with the I-Neb AAD, the content of one 1-ml ampoule of Ventavis 
20 microgram/ml, showing two coloured rings (–yellow-red), will be transferred into the appropriate 
nebuliser medication chamber with golden coloured latch together with the golden colour disc 
immediately before use.  
 



66 

Since the I-Neb AAD system can be used for Ventavis 10 microgram/ml and Ventavis 20 
microgram/ml, the table below provides a summary of the user instructions of the I-Neb for the 2 
concentrations of Ventavis: 
 

Drug product Ampoule   coloured rings Dosage 
I-Neb AAD 

Medication  
chamber latch 

Control disc 

Ventavis 10 mcg/ml 1 ml ampoule white-yellow ring 

2.5 mcg 
 red red 

5 mcg 
 purple purple 

Ventavis 20 mcg/ml 1 ml ampoule 
yellow-red ring 5 mcg golden  golden  

 
The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems, 
which provide different nebulisation characteristics of iloprost solution, have not been established. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET