Label: information for the user

Ventavis 10 micrograms/ml solution for inhalation by nebulizer

Iloprost

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

What is Ventavis

The active ingredient of Ventavis is iloprost. Iloprost imitates a natural substance of the body called prostacyclin. Ventavis inhibits unwanted blockage or narrowing of blood vessels and allows more blood to flow through the blood vessels.

What is Ventavis used for

Ventavis is used to treat moderate cases of primary pulmonary hypertension (PPH) in adult patients. PPH is a type of pulmonary hypertension in which the cause of the increased blood pressure is unknown.

It is a disease in which the blood pressure is too high in the blood vessels located between the heart and the lungs.

Ventavis is used to improve the ability to exercise (i.e., the ability to perform physical activities) and the symptoms of this disease.

How Ventavis works

When inhaling the aerosol, Ventavis reaches the lungs, where it acts more effectively on the artery located between the heart and the lungs. By improving blood flow, oxygen supply to the body is improved and the heart's workload is reduced.

No use Ventavis

• if you are allergicto iloprost or to any of the other ingredients of this medicine (including those listed in section 6),
• if you have a risk of bleeding–for example, if you have an active ulcer in the stomach or in the first part of the small intestine (duodenal ulcers), if you have suffered a physical injury (trauma), if you are at risk of suffering a subarachnoid hemorrhage,

• if you have a heart problem, such as for example

• • you have had a heart attack in the last six months,
  • you have a weak heart (decompensated heart failure) that is not under close medical supervision,
  • you have severe arrhythmias,
  • you have a heart valve defect (congenital or acquired) that makes the heart not work properly (not related to pulmonary hypertension),
• if you have had a stroke in the last 3 months or any otherevent that has reduced blood flow to the brain (e.g., transient ischemic attack),

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

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Ventavis:

• The inhalation of Ventavis could trigger breathing difficulties (see section 4), especially in patients with bronchospasm (a sudden narrowing of the small airway muscles) and wheezing. Inform your doctorif you have a lung infection, severe asthma or other chronic lung disease.Your doctor will closely monitor you.

• Your blood pressure will be taken before treatment and if it is too low(less than 85 mmHg for the highest value) do not start the Ventavis therapy.

• Generally, you will have totake special care to avoid the effects of low blood pressure, such as fainting and dizziness:
• • Inform your doctor if you are taking other medicines, as the combination with Ventavis may lower your blood pressure even further (see below “Ventavis use with other medicines”).

• • Get up slowly from a chair or bed.
  • If you tend to faint when getting up from bed, it may be helpful to take the first dose of the day while still lying down.
  • If you tend to have fainting spells, avoid any exceptional effort, for example during physical exercise; it may be helpful to inhale Ventavis before doing so.
• The fainting spells may be due to the underlying disease. Inform your doctor if they worsen, as he/she may consider adjusting your dose or changing your treatment.

• if you have heart disease, such as right heart failure and notice that your disease is worsening, tell your doctor. The symptoms may include swellingof the feet and ankles, difficulty breathing, palpitations, need to urinate more frequently at night or edema. Your doctor will consider whether you need to change your treatment.

• if you have difficulty breathing, coughing up blood and/or sweating excessively, these may be signs that you have water in your lungs (pulmonary edema).Stop using Ventavis and tell your doctor immediately. He/she will investigate the cause and take appropriate measures.

• if you have severe liver or kidney problems that require dialysis, inform your doctor. You may be gradually changed to the prescribed dose or you may be prescribed a lower dose of Ventavis than other patients (see section 3 “How to use Ventavis”).

Contact of Ventavis with the skin or ingestion of Ventavis

• DO NOT let the Ventavis solution come into contact with the skin or eyes. If this occurs, wash the skin or eyes immediately with plenty of water.

• DO NOT drink or swallow the Ventavis solution.

If this occurs accidentally, drink plenty of water and inform your doctor.

Children and adolescents

The safety and efficacy of Ventavis have not been established in children up to 18 years.

Other medicines and Ventavis

Inform your doctor or pharmacist if you areusing, have used recently or may need to use any other medicine. Ventavis may affect the way other medicines work and vice versa.

Inform your doctor if you are taking:

• Medicines for the treatment of hypertension or heart disease, such as

Your blood pressure may drop too low.

Your doctor may adjust your dose.

• Medicines that make the blood less thick or that inhibit its coagulation,such as

• defibrotide

Your doctor will closely monitor you.

Before taking any medicine, consult your doctor or pharmacist, who has more information on the medicines with which you should be cautious or that you should avoid when using Ventavis.

Use of Ventavis with food and drinks

It is not expected that food or drinks will affect Ventavis. However, you should avoid eating or drinking during inhalation.

Pregnancy

• if you have pulmonary hypertension, avoid becoming pregnant, as pregnancy maycause your disease to worsen and even put your life at risk.

• if you may become pregnant, use reliable contraception from the start of treatment and during treatment.
• if you are pregnant, think you may be pregnant or intend to become pregnant, inform your doctor immediately. Ventavis should only be usedduring pregnancy if your doctor decides that the potential benefit outweighs the possible risks for you and the fetus.

Breastfeeding

The passage of Ventavis into breast milk is unknown. It cannot be ruled out that there is a potential risk in infants and it is preferable to avoid breastfeeding during Ventavis treatment.

Consult your doctor or pharmacist before using any medicine.

Newborns, infants and pregnant women should not be in the same room while you are inhaling Ventavis.

Driving and operating machines

Ventavis reduces blood pressure and may cause dizziness or instability in some people.

Do not drive or use tools or machines if you notice these effects.

Ventavis contains ethanol

Ventavis 10 micrograms/ml contains 0.81 mg of alcohol (ethanol) in each ml, which is equivalent to 0.081% (v/v). The amount of 0.81 mg of alcohol in 1 ml of this medicine is equivalent to less than 1 ml of beer or wine.

The small amount of alcohol in this medicine does not produce any noticeable effect.

The treatment with Ventavis should only be initiated by a doctor with experience in the treatment of pulmonary hypertension.

How much to inhale and for how long

Follow exactly the administration instructions of this medication indicated by your doctor.

In case of doubt, consult your doctor again.

The dose you need of Ventavis and the duration of treatment you need depends on your condition. Your doctor will advise you. Do not change the recommended dose without consulting your doctor first.

Different nebulizer devices can be used to administer Ventavis. Depending on the type of device used and the prescribed dose, it is appropriate to use 1 ml or 2 ml of Ventavis 10 micrograms/ml.

• Breelib

When starting treatment with Ventavis or if you change from an alternative device, the first inhalation should be done with Ventavis 10 micrograms/ml (ampoule of 1 ml with white and yellow rings). If you tolerate this dose well, your next inhalation will be with Ventavis 20 micrograms/ml (ampoule with yellow and red rings). You should continue with this dose.

If you cannot tolerate the inhalation of Ventavis 20 micrograms/ml, consult your doctor, who may decide that you should receive Ventavis 10 micrograms/ml (ampoule of 1 ml).

Most people should perform 6 to 9 inhalation sessionsspread throughoutthe day. The duration of each inhalation session with Breelib is usually 3 minutes.

Your doctor will monitor your treatment when you start using the Breelib nebulizer to ensure that you tolerate the dose and inhalation speed well.

• I-Neb AAD (ampoule of 1 ml with white and yellow rings)

Generally, when starting treatment with Ventavis, the first dose inhaled should be

2.5 micrograms of iloprost released by the nebulizer mouthpiece. If you tolerate this dose well, the dose should be increased to 5 micrograms of iloprost and you should continue with this dose. If you cannot tolerate the 5 microgram dose, the dose should be reduced to 2.5 micrograms.

Most people should perform 6 to 9 inhalation sessionsspread throughoutthe day. The duration of each inhalation session with I-Neb AAD is usually 4 to 10 minutes depending on the prescribed dose.

• Venta-Neb (ampoule of 2 ml with white and pink rings)

Generally, when starting treatment with Ventavis, the first dose inhaled should be

2.5 micrograms of iloprost released by the nebulizer mouthpiece. If you tolerate this dose well, the dose should be increased to 5 micrograms and you should continue with this dose. If you cannot tolerate the 5 microgram dose, the dose should be reduced to 2.5 micrograms.

Most people should perform 6 to 9 inhalation sessionsspread throughoutthe day. The duration of each inhalation session with Venta-Neb is usually 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

No dose adjustment is necessary in patients with mild or moderate renal impairment (patients with a creatinine clearance > 30 ml/min).

If you have severe kidney problems and require dialysis or have liver problems, your doctor will introduce Ventavis gradually and may prescribe fewer inhalations per day. Start treatment by inhaling 2.5 micrograms of iloprost, using a 1 ml ampoule of Ventavis

10 micrograms/ml (with white and yellow rings). Use dosing intervals of 3-4 hours (corresponding to a maximum of 6 administrations per day). Your doctor may then shorten the dosing intervals as needed based on how well you tolerate the treatment. If your doctor decides to increase the dose to 5 micrograms, the dosing intervals should be established again at 3-4 hours and shortened as needed based on how well you tolerate the treatment.

If you notice that the effect of Ventavis is too strong or too weak,consult your doctor or pharmacist.Ask your doctor to have someone help you familiarize yourself with the use of the nebulizer. Do not change to another nebulizer without consulting the doctor treating you.

How to inhale

In each inhalation session, you should use a new ampoule of Ventavis. Just before starting to inhale, break the glass ampoule and pour the solution into the medication chamber following the nebulizer usage instructions.

Follow the instructions that accompany the nebulizer, especially those related to hygiene and cleaning of the nebulizer.

Follow exactly the administration instructions of Ventavis indicated by your doctor.

• Ventavis 10 micrograms/ml solution for inhalation by nebulizer is inhaled using the nebulizers prescribed by your doctor (Breelib, Venta-Neb or I-Neb AAD).

• The nebulizer transforms the Ventavis solution into an aerosol that is inhaled through the mouth.
• To inhale, you must use a mouthpiece to avoid Ventavis coming into contact with your skin. Do not use a mask.
• Follow the instructions that accompany the nebulizer carefully. Consult your doctor or pharmacist if you have any doubts.

• Any remaining Ventavis solution in the nebulizer after inhalation should be discarded (see section 5).

Ventilation of the room

Make sure to ventilate or air the room in which you have taken Ventavis treatment. Other people may be accidentally exposed to Ventavis through the room air. Especially,

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. Follow the nebulizer usage instructions for filling.

• I-Neb AAD

1. Immediately before inhalation, break the glass ampoule containing 1 ml of solution, which has two color rings (white-yellow), and pour all its contents into the medication chamber of the nebulizer.

1. The pre-set dose administered by the I-Neb AAD system is controlled by the medication chamber, in combination with a control disk. There are two medication chambers with different color codes. For each medication chamber, there is a control disk with its corresponding color code:

• • For the dose of2.5 micrograms, the medication chamberwith the red latch is usedtogether with the red control disk.
  • For the dose of5 micrograms, the medication chamberwith the purple latch is usedtogether with the purple control disk.
• To ensure that you receive the prescribed dose, check the color of the medication chamber and the color of the control disk. These should have the same color, either red for the 2.5 microgram dose or purple for the 5 microgram dose.

The following table includes a summary of the instructions for using I-Neb:

• Venta-Neb

1. Immediately before inhalation, break the glass ampoule containing 2 ml of solution, which has two color rings (white-pink), and pour all its contents into the medication chamber of the nebulizer.

1. Two programs can be used:
2. Your doctor will adjust the Venta-Neb system program to your needs so that you receive the prescribed dose for you.

• • P2 Program 2: 2.5 micrograms of active ingredient in the mouthpiece, 10 inhalation cycles.
• To obtain the optimal droplet size for the administration of Ventavis, the green deflecting plate should be used.

For more details, see the nebulizer device manual or consult your doctor.

If you use more Ventavis than you should

Using more Ventavis than you should may cause dizziness, headache, flushing (redness of the face), nausea (feeling of discomfort), jaw or back pain.

You may also experience a decrease or increase in blood pressure, bradycardia (decrease in heart rate), tachycardia (increase in heart rate), vomiting, diarrhea, or pain in the limbs. If any of these occur when you have used more Ventavis than you should:

• Interrupt the inhalation session.

• Consult your doctor.

Your doctor will monitor and treat any resulting symptoms. No specific antidote is known.

If you forget to use Ventavis

Do not take a double dose to compensate for the missed doses. Consult your doctor on what to do.

If you interrupt treatment with Ventavis

Consult your doctor before interrupting or stopping treatment.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The followingserious side effectsmay occur. If they occur, consult your doctor immediately:

Very common(may affect more than 1 in 10 people):

• Very frequent episodes of bleeding (mainly nosebleeds [epistaxis] and coughing up blood [hemoptysis]) may occur, especially if you are taking treatment to thin your blood (anticoagulants). The risk of bleeding may increase in patients treated at the same time with platelet aggregation inhibitors or anticoagulants (see also section 2). In very rare cases, fatal cases have been reported that included intracranial hemorrhage (intracranial hemorrhage and cerebral hemorrhage).

Common(may affect up to 1 in 10 people):

• Loss of consciousness (syncope) is a symptom of the underlying disease, but it may also occur during treatment with Ventavis (see also section 2 “Warnings and precautions” for recommendations on what you can do to avoid these symptoms).

• Low blood pressure (hypotension)

Frequency not known(cannot be estimated from the available data):

• Bronchospasm (sudden constriction of the small airway muscles) and wheezing (see also section 2 “Warnings and precautions”).

The following is a list of other possible side effects based on their probability of occurrence:

Very common:may affect more than 1 in 10 people

• vasodilation (dilation of blood vessels). Symptoms may include flushing or redness of the face
• chest discomfort / chest pain
• cough
• headache
• nausea
• jaw pain / jaw muscle spasm (trismus)
• swelling of the extremities (peripheral edema)

Common:may affect up to 1 in 10 people

• difficulty breathing (dyspnea)

• dizziness

• vomiting

• diarrhea

• throat pain (pharyngolaryngeal irritation)

• throat irritation

• mouth and tongue irritation, including pain

• skin rash

• rapid heart rate (tachycardia)

• awareness of rapid or intense heart rate (palpitations)

Frequency not known:the frequency cannot be estimated from the available data.

• reduction in the number of platelets in the blood (thrombocytopenia)

• hypersensitivity (i.e., allergy)

• alterations in taste (dysgeusia)

Other possible side effects

• Swelling mainly of the ankles and legs due to fluid retention (peripheral edema) is a very common symptom of the underlying disease, but it may also occur during treatment with Ventavis.

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directlytothrough the national notification system included in theAppendix V.By reportingside effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and ampule.

No special storage conditions are required.

Any remaining Ventavis solution in the nebulizer after inhalation should be discarded.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.

Composition of Ventavis:

• The active ingredientis iloprost.

1 ml of solution contains 10 micrograms of iloprost (as iloprost trometamol).

Each ampoule of 1 ml contains 10 micrograms of iloprost.

Each ampoule of 2 ml contains 20 micrograms of iloprost.

• The other components aretrometamol, ethanol, sodium chloride, hydrochloric acid for pH adjustment and water for injection preparations.

Appearance of the product and contents of the package:

Ventavis is a transparent, colorless solution for inhalation by nebulizer with the nebulizers Breelib, I-Neb or Venta-Neb.

Ventavis 10 micrograms/ml is supplied in colorless ampoules, containing 1 ml or 2 ml of solution for inhalation by nebulizer.

Ventavis 10 micrograms/ml is available in the following pack sizes:

• Ampoules of 1 ml for use with the nebulizers Breelib or I-Neb:
• • Package containing 30 or 42 ampoules for use with the nebulizers Breelib and I-Neb.
  • Multi-pack containing 168 (4 x 42) ampoules for use with the nebulizers Breelib and I-Neb.

The ampoules containing 1 ml are marked with two colored rings (white-yellow).

• Ampoules of 2 ml for use with the nebulizer Venta-Neb:
• • Package containing 30, 90, 100 or 300 ampoules.
  • Multi-pack containing 90 (3 x 30) or 300 (10 x 30) ampoules.

The ampoules containing 2 ml are marked with two colored rings (white-pink).

Only some pack sizes may be marketed.

Marketing Authorization Holder:

Bayer AG

51368 Leverkusen

Germany

Responsible for manufacturing:

Berlimed S.A.

Francisco Alonso 7

Poligono Industrial Santa Rosa

28806 Alcala de Henares

Madrid

Spain

For further information on this medicinal product, please contact the local representative of the marketing authorization holder.

België / Belgique / BelgienLietuva

Bayer SA-NVUAB Bayer

Tél/Tel: +32-(0)2-535 63 11Tel. +37 05 23 36 868

????????Luxembourg / Luxemburg

????? ???????? ????Bayer SA-NV

???. +359 02-424 72 80Tél/Tel: +32-(0)2-535 63 11

Ceská republikaMagyarország

Bayer s.r.o.Bayer Hungária KFT

Tel: +420 266 101 111Tel.:+36 14 87-41 00

DanmarkMalta

Bayer A/SAlfred Gera and Sons Ltd.

Tlf: +45-45 23 50 00Tel: +35 621 44 62 05

DeutschlandNederland

Bayer Vital GmbHBayer B.V.

Tel: +49 (0)214-30 513 48Tel: +31-(0)297-28 06 66

EestiNorge

Bayer OÜBayer AS

Tel: +372 655 8565Tlf. +47 23 13 05 00

Ελλ?δαÖsterreich

Bayer Ελλ?ς ΑΒΕΕBayer Austria Ges. m. b. H.

Τηλ: +30 210 61 87 500Tel: +43-(0)1-711 46-0

EspañaPolska

Bayer Hispania S.L.Bayer Sp. z o.o.

Tel: +34-93-495 65 00Tel.: +48 22 572 35 00

FrancePortugal

Bayer HealthCareBayer Portugal, Lda.

Tél(N° vert): +33-(0)800 87 54 54Tel: +351 21 416 42 00

HrvatskaRomânia

Bayer d.o.o.SC Bayer SRL

Tel: + 385-(0)1-6599 900Tel: +40 21 529 59 00

IrelandSlovenija

Bayer LimitedBayer d. o. o.

Tel: +353 1 216 3300Tel.: +386 (0)1 58 14 400

ÍslandSlovenská republika

Icepharma hf.Bayer, spol. s r.o.

Sími: +354 540 8000Tel: +421 2 59 21 31 11

ItaliaSuomi/Finland

Bayer S.p.A.Bayer Oy

Tel: +39 02 397 81Puh/Tel: +358 20 785 21

Κ?προςSverige

NOVAGEM LimitedBayer AB

Τηλ: +357 22 48 38 58Tel: +46 (0) 8 580 223 00

LatvijaUnited Kingdom

SIA BayerBayer plc

Tel: +371 67 84 55 63Tel: +44 (0)118 206 3000

Date of the last review of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

There are also links to other websites on rare diseases and orphan drugs.

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