Ventavis 10 microgram/ml nebuliser solution

What Ventavis is

Ventavis is a nebuliser solution. The solution is changed into an aerosol mist by a special machine called a nebuliser.

What Ventavis is used for

Ventavis is used to treat moderate cases of primary pulmonary hypertension (PPH). This is a condition where blood pressure is too high in the blood vessels between the heart and the lungs.

How Ventavis works

The active substance of Ventavis (iloprost) imitates a natural substance in the body called prostacyclin. Ventavis and prostacyclin inhibit unwanted blocking or narrowing of blood vessels and allow more blood to flow through the vessels.

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.

Do NOT use Ventavis if you:

- are allergic(hypersensitive) to iloprost or any of the other ingredients of Ventavis (see also section 6. Further information).
- 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 aninjury, if you are at risk of bleeding within the skull.
- have the disease due to a blocked or narrowed vein(venous occlusive disease).. - have had a strokewithin the last 3 months, or any other occurrence that reduced the blood supply to the brain (e.g. transient ischemic attack).
- have a heart problem, such as:

• a heart attack within the last six months
• severe changes in heart rate
• poor blood flow to the heart muscles ( severe coronary heart disease or unstable angina). Symptoms can be chest pain.
• a weak heart (decompensated cardiac failure) which isnot under close medical observation.
• a defect of the heart valves that causes the heart to work poorly ( not related to pulmonary hypertension). - are pregnant or breast-feeding.

Take special care with 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 closely monitor you. - If your blood pressure is too low (less than 85 mmHg for the upper value) you should not start the therapy with Ventavis.
• In general, you will need to take special care to try and avoideffects 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 further lower your blood pressure (see below "Taking or using other medicines"). - 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 a right heart failure, and feel that your disease is worsening, tell your doctor. Symptoms can be swelling of feet and ankles, shortness of breath, palpitations, urinating more frequently at night. 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") .

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.

Taking or using other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

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 e.g. 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 - to lower fever and relieve pain, and heparin, coumarin-type anticoagulants e.g. warfarin, phenprocoumon as well as others.

Ask your doctor or pharmacist for advice before taking any medicine. He/she has more information on medicines to be careful with or avoid when using Ventavis.

Using 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 are pregnant, or think you might be, tell your doctor straight away. Ventavis must not be used by pregnant women (see section 2. Do not use Ventavis).
• If you could get pregnant, use reliable contraception from the time you start treatment and during treatment (ask your doctor).

Breast-feeding:

Stop breast-feeding when you start treatment. Ventavis must not be given to women who are breast-feeding, since it is not known whether the active substance is passed on through breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Newborns, infants, and pregnant women should not be subjected to Ventavis in the room air.

These persons should not remain in a closed room where Ventavis is being administered to a patient.

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.

Important information about some of the ingredients of Ventavis:

This medicinal product contains small amounts of ethanol (alcohol) (less than 100 mg per dose).

How to use Ventavis:

Always take Ventavis exactly as your doctor has told you.

• Ventavis nebuliser solution is inhaled using the nebulisers your doctor prescribed (either the HaloLite, the Prodose, 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 extra instructions that come with the nebuliser. Check with your doctor or pharmacist if you are unsure.
• Dispose of any Ventavis solution that you do not use in one inhalation session (see Section 5).

Use in children and adolescents:

Ventavis is not recommended for children or adolescents.

Caution:

Do not let Ventavis solution come into contact with your skin or eyes. If it does, rinse the skin or your eyes immediately with water.
Do not drink Ventavis solution. If you swallow it by accident, drink plenty of water and contact your doctor (see also ?If you take more Ventavis than you should?).

How much to inhale and for how long:

• The dose of Ventavis and the duration of treatment that is right for you depends on your individual condition. Your doctor will advise you.
• Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation session will usually last about 4 to 10 minutes depending on the prescribed dose.
• If you have liver problems or very severe kidney problems, your doctor will introduce you to Ventavis gradually and possibly prescribe fewer daily inhalations.
• - 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.

Room ventilation

Be sure to ventilate or air the room in which you have taken your Ventavis treatment. Other persons might accidentally be exposed to Ventavis through the room air. In particular, newborns, infants, and pregnant women should not be subjected to Ventavis.

For HaloLite and ProDose systems:

1. Just before you start to inhale, break open the glass ampoule containing 2 ml solution, which shows two coloured rings (white-pink), and transfer the complete contents into the nebuliser medication chamber.

2. You should run the inhalation cycle twice if you require a high dose (5 micrograms) and once if you require a low dose (2.5 micrograms). Independent of the dose the filling volume is always the contents of one glass container.

3. The inhalation time depends on your breathing pattern.

Device Dose of iloprost at mouthpiece Estimated Inhalation time frequency of 15 breaths per minute HaloLite 2.5 micrograms 5 micrograms 4 to 5 min 8 to 10 min Prodose 2.5 micrograms 5 micrograms 4 to 5 min 8 to 10 min

For the Venta-Neb system:

1. Just before you start to inhale, break open the glass container and transfer the complete contents into the nebuliser medication chamber.

2. Two programs can be operated:

3. Your doctor will adjust Venta-Neb to the program you need to receive the dose prescribed for you. P1 Program 1: 5.0 micrograms active substance on the mouth piece 25 inhalation cycles. P2 Program 2: 2.5 micrograms 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 micrograms 5 micrograms 4 min 8 min

For the I-Neb AAD system:

1. Just before you start to inhale, break open the glass ampoule containing 1 ml solution, which shows two coloured rings (white - yellow), and transfer 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 micrograms dose the medication chamber (350 microliter) with the red latch is used together with the red control disc.
• For the 5 micrograms dose the medication chamber (650 microliter) 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 micrograms 5 micrograms 3.2 min 6.5 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 a decrease in blood pressure with symptoms such as dizziness or fainting.
You may also experience headache, reddening of the face (flushing), feeling sick (nausea), vomiting or diarrhoea. An increase in blood pressure, reduced or increased heart rate and limb or back pain may also be possible. If any of these happens:
- stop the inhalation session
- talk to your doctor

If you forget to use Ventavis:

You should 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 product, ask your doctor or pharmacist.

Like all medicines, Ventavis can cause side effects, although not everybody gets them.

Very common: affects more than 1 user in 10.
Common: affects 1 to 10 users in 100.
Frequency not known:frequency can not be estimated from the available data

The following side effects may occur. In this case ask your doctor

Fainting syncope is a common symptom of the illness itself but can also occur during treatment with Ventavis.see also section 2 Take special care with Ventavis , for advice on what you can do to try and avoid this. Common low blood pressure hypotension Bleeding events may very commonly occur, especially if you are also taking blood-thinning medicines anticoagulants Frequency not known bronchospasm sudden constriction of the muscles in the walls of the small airways and wheezing see also section 2 Take special care with Ventavis

Below we list other possible side effects by how likely they are:

Very common side effects

• widening of the blood vessels (vasodilatation). Symptoms can be flushing or reddening of the face.
• chest discomfort / chest pain
• increase in coughing
• headache
• nausea
• pain in jaw/spasm of the jaw muscles (trismus)

Common effects

• breathing difficulties (dyspnoea)
• dizziness
• vomiting
• diarrhoea,
• pain when swallowing (pharyngolaryngeal irritation and throat irritation)
• mouth and tongue irritation
• rash

Side effects for which frequency is not known

-

• Hypersensitivity (i.e. allergy)
• Disturbed sense of taste ( dysgueusia)

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.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Keep out of the reach and sight of children.
Do not use Ventavis after the expiry date which is stated on the pack.
There are no special storage instructions.

Discard any Ventavis solution that you do not use in inhalation session.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Ventavis contains:

- The active substance is iloprost.
1 ml solution contains 10 micrograms iloprost (as iloprost trometamol).
Each ampoule with 1 ml contains 10 micrograms iloprost.
Each ampoule with 2 ml contains 20 micrograms iloprost.

- The other ingredients are trometamol, ethanol 96%, sodium chloride, hydrochloric acid for pH adjustment, and water for injections.

Ventavis is provided in colourless ampoules (type I glass), containing either 1 ml or 2 ml nebuliser solution.

What Ventavis looks like and content of the pack:

Ventavis is a clear, colourless nebuliser solution for inhalation.

Ventavis is available in packs containing:

• 30, 90, 100, or 300 ampoules with 2 ml for the use with HaloLite, Prodose and Venta-Neb. The ampoules containing 2 ml show two coloured rings (white ? pink).
• or 30 or 168 ampoules with 1 ml for use with the I-Neb nebuliser. The ampoules containing 1 ml show two coloured rings (white - yellow).

Not all pack-sizes may be marketed.

Marketing Authorisation Holder:
Bayer Schering Pharma AG, D-13342 Berlin, Germany

Manufacturer:
Berlimed S.A., Poligono Industrial Santa Rosa s/n, 28806 Alcalá de Henares, Madrid, Spain

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien Bayer SA-NV TélTel 32-02-535 63 11 LuxembourgLuxemburg Bayer SA-NV TélTel 32-02-535 63 11

. 359-02-81 401 01 Magyarország Bayer Hungária KFT Tel. 36-1-487 4100

eská republika Bayer s.r.o. Tel 420-266 101 111 Malta. Alfred Gera and Sons Ltd. Tel 35-621 44 62 05

Danmark Bayer AS Tlf 45-45 235 000 Nederland Bayer B.V., Bayer Schering Pharma Tel 31-0297-28 06 66

Deutschland Bayer Vital GmbH Tel 49-0214-30 513 48 Norge Bayer AS Tlf 47-24 11 18 00

Eesti Bayer OÜ Tel 372-655 85 65 Österreich Bayer Austria Ges.m.b.H. Tel 43-01-711 460

Bayer 30-210-618 75 00 Polska Bayer Sp. z o.o. Tel. 48-22-572 35 00

España Bayer Hispania S.L. Tel 34-93-495 65 00 Portugal Bayer Portugal S.A. Tel 351-21-416 42 00

France Bayer Santé Tél. 33-03-28 16 34 00 Romania SC Bayer SRL Tel. 40-021-528 59 00

Ireland Bayer Limited Tel 353-01-2999 313 Slovenija Bayer d.o.o. Tel 386-01-58 14 400

Ísland Icepharma hf. Sími 354-540 8000 Slovenská republika Bayer, spol. s r.o. Tel. 421-02-59 21 31 11

Italia Italfarmaco S.p.A. Tel 39-02-644 31 SuomiFinland Bayer Oy, Bayer Schering Pharma PuhTel 358-020-78521

NOVAGEM Limited 357-22-747 747 Sverige Bayer AB Tel 46-08-580 223 00

Latvija SIA Bayer Tel 371-67 84 55 63 United Kingdom Bayer plc Tel 44-01635-56 30 00

Lietuva

UAB Bayer
Tel. +370-5-23 36 868

This leaflet was last approved in

This medicine has been authorised under ?exceptional circumstances?.
This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.
The European Medicines Agency (EMA) will review any new information on the medicine every year and this leaflet will be updated as necessary.

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The following information is intended for medical or healthcare professionals only:

Instructions for use and handling

Two compressed air nebuliser systems, HaloLite and Prodose, have been shown to be suitable nebulisers for the administration of Ventavis. For each inhalation session the content of one ampoule containing 2 ml of Ventavis nebuliser solution will be transferred into the nebuliser medication chamber immediately before use. HaloLite and Prodose are dosimetric systems. They stop automatically after the pre-set dose has been delivered. The inhalation time depends on the patient?s breathing pattern.

Device Dose of iloprost at mouthpiece Estimated Inhalation time frequency of 15 breaths per minute HaloLite 2.5 micrograms 5 micrograms 4 to 5 min 8 to 10 min Prodose 2.5 micrograms 5 micrograms 4 to 5 min 8 to 10 min

For a dose of 5 micrograms iloprost at mouthpiece it is recommended to complete two inhalation cycles with 2.5 micrograms pre-set dose program with a filling of one ampoule containing 2 ml Ventavis nebuliser solution, which shows two coloured rings (white ? pink).

For details refer to the instruction manuals of the HaloLite and Prodose nebuliser.

VentaNeb, a portable ultrasonic battery-powered nebuliser, has also been shown to be suitable for the administration of Ventavis. 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 nebuliser solution and showing two coloured rings (white ? pink) will be transferred into the nebuliser medication chamber immediately before use.

Two programs can be operated:
P1 Program 1: 5,0 micrograms active substance on the mouth piece 25 inhalation cycles. P2 Program 2: 2,5 micrograms active substance on the mouth piece 10 inhalation cycles. The selection of the pre set program is made by the physician.

VentaNeb 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 VentaNeb 2.5 micrograms 5 micrograms 4 min 8 min

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. The I-Neb AAD nebuliser has also been shown to be suitable for the administration of Ventavis. 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 micrograms iloprost.

The pre-set dose provided by the I-Neb AAD system is controlled by the medication chamber and 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 micrograms dose the medication chamber (350 microliter) with the red latch is used together with the red control disc.
For the 5 micrograms dose the medication chamber (650 microliter) 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, showing two coloured rings (white - yellow), will be transferred into the appropriate nebuliser medication chamber immediately before use.

Device Dose of iloprost at mouthpiece Estimated Inhalation time I-Neb AAD 2.5 micrograms 5 micrograms 3.2 min 6.5 min

Since the I-Neb nebuliser has been shown to produce an aerosol with slightly different physical characteristics to those of HaloLite, Prodose and VentaNeb devices and a faster delivery of the solution, patients stabilized on one nebuliser should not switch to another nebuliser without supervision by the treating physician.

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.