ILOPROST 20 mcg/ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Iloprost Zentiva, 20 micrograms/ml, Nebuliser Solution
   1. Read all of this leaflet carefully before using this medicine because it contains important information for you.
   2. Contents of the pack and other information
3. What Iloprost Zentiva is and what it is used for
   1. What Iloprost Zentiva is
   2. What Iloprost Zentiva is used for
   3. How Iloprost Zentiva works
4. What you need to know before you use Iloprost Zentiva
   1. Do not use Iloprost Zentiva
   2. Warnings and precautions
   3. Contact with skin or eyes or swallowing Iloprost Zentiva
   4. Children and adolescents
   5. Iloprost Zentiva with other medicines
   6. Taking Iloprost Zentiva with food and drink
   7. Pregnancy
   8. Breast-feeding
   9. Newborns, infants and pregnant women should not be in the same room where the patient is inhaling Iloprost Zentiva.
   10. Driving and using machines
   11. Iloprost Zentiva contains ethanol
5. How to use Iloprost Zentiva
   1. Dose and duration of treatment
   2. Method of inhalation
   3. Using more than the recommended dose of Iloprost Zentiva
   4. Missing a dose of Iloprost Zentiva
   5. Stopping treatment with Iloprost Zentiva
6. Possible side effects
   1. Other possible symptoms
   2. Reporting of side effects
7. How to store Iloprost Zentiva
8. Contents of the pack and other information
   1. What Iloprost Zentiva contains
   2. What Iloprost Zentiva looks like and contents of the pack
   3. Marketing Authorisation Holder
   4. Manufacturer
   5. This medicinal product is authorised in the Member States of the European Economic Area under the following names:
   6. Poland, Czech Republic,
   7. Italy
   8. Germany
   9. United Kingdom
   10. For further information about this medicine, please contact the Marketing Authorisation Holder in your country:

Package Leaflet: Information for the User

Iloprost Zentiva, 20 micrograms/ml, Nebuliser Solution

Iloprost

Read all of this leaflet carefully before 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.

Contents of the pack and other information

• 1. What Iloprost Zentiva is and what it is used for
• 2. What you need to know before you use Iloprost Zentiva
• 3. How to use Iloprost Zentiva
• 4. Possible side effects
• 5. How to store Iloprost Zentiva
• 6. Contents of the pack and other information

1. What Iloprost Zentiva is and what it is used for

What Iloprost Zentiva is

The active substance of Iloprost Zentiva is iloprost. It mimics the action of a naturally occurring substance in the body called prostacyclin. Iloprost Zentiva prevents unwanted narrowing or blockage of blood vessels, allowing more blood to flow through the vessels.

What Iloprost Zentiva is used for

Iloprost Zentiva is used to treat moderate pulmonary arterial hypertension in adult patients. Pulmonary arterial hypertension is a type of high blood pressure in the blood vessels between the heart and lungs. In this disease, the blood pressure in the blood vessels between the heart and lungs is too high.

How Iloprost Zentiva works

Inhaling the aerosol formed by Iloprost Zentiva allows the medicine to reach the lungs, where it can work most effectively in the artery between the heart and lungs. Improved blood flow leads to better oxygen supply to the body and reduces the strain on the heart.

2. What you need to know before you use Iloprost Zentiva

Do not use Iloprost Zentiva

• If you are allergicto iloprost or any of the other ingredients of this medicine (listed in section 6).
• If you have a risk of bleeding- for example, if you have an active stomach or duodenal ulcer, if you have had recent physical trauma, or if you are at risk of bleeding in the brain.
• If you have heart disease, such as:
• poor blood flow to the heart muscle (severe coronary artery disease or unstable angina). Symptoms may include chest pain.
• heart attack in the last 6 months.
• weak heart (uncontrolled heart failure), if this condition is not controlled by your doctor.
• severe, unstable heart rhythm.
• heart valve problems (congenital or acquired) that make the heart work poorly (not related to pulmonary hypertension).
• If you have had a stroke or any other event that reduced blood flow to the brain(such as a transient ischaemic attack) in the last 3 months.
• If your pulmonary hypertension is caused by narrowing or blockage of a vein(thromboembolic disease).

Warnings and precautions

Before starting treatment with Iloprost Zentiva, you should discuss it with your doctor, pharmacist or nurse:

• Inhalation of Iloprost Zentiva may cause difficulty breathing (see section 4), especially in patients with bronchospasm (sudden constriction of the muscles in the walls of the small airways) and wheezing. You should tell your doctor if you have 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(below 85 mmHg for the higher value), you should not start treatment with Iloprost Zentiva.
• You should be careful to avoid symptoms of low blood pressure, such as fainting and dizziness:
• You should tell your doctor about all the medicines you are taking, as their combined effect with Iloprost Zentiva may further lower your blood pressure (see below "Other medicines and Iloprost Zentiva").
• Get up slowly when getting up from a chair or bed.
• If you experience fainting immediately after getting up from bed, it may be helpful for you to take the first dose of the day while still in bed.
• If you tend to faint, you should avoid overexerting yourself, such as during physical exertion. It may be helpful to use Iloprost Zentiva before physical exertion. Fainting can be a symptom of the underlying disease. If fainting worsens, you should inform your doctor. Your doctor may consider adjusting the dose or changing the treatment.
• If you have heart disease, such as right heart failure and you feel that your condition is worsening, you should inform your doctor. Symptoms may include swollen feet and ankles, shortness of breath, palpitations, more frequent urination at night or swelling. Your doctor may consider changing the treatment.
• If you experience difficulty breathing, coughing up blood and (or) excessive sweating, these may be symptoms of fluid in the lungs(pulmonary oedema). You should stop using Iloprost Zentiva and immediately inform your doctor. Your doctor will investigate the cause and take appropriate action.
• If you have liver or kidney problems that require dialysis, you should tell your doctor. Your doctor may gradually introduce the target dose or prescribe a lower dose of Iloprost Zentiva than is usually given to other patients (see section 3 "How to use Iloprost Zentiva").

Contact with skin or eyes or swallowing Iloprost Zentiva

• Do not allow the Iloprost Zentiva solution to come into contact with your skin or eyes. If this happens, rinse your skin or eyes immediately with plenty of water.
• Do not drink or swallow the Iloprost Zentiva solution. If you accidentally swallow it, drink plenty of water and contact your doctor.

Children and adolescents

The safety and efficacy of iloprost in children under 18 years of age have not been established.

Iloprost Zentiva with other medicines

Tell your doctor or pharmacistabout all the medicines you are taking, or have recently taken, and about any medicines you plan to take. The combined effect of Iloprost Zentiva and some medicines may affect you. You should tell your doctor if you are taking any of the following medicines:

• Medicines for high blood pressure or heart disease, such as:
• beta blockers,
• nitrate medicines that widen blood vessels,
• ACE inhibitors. Blood pressure may decrease further. Your doctor may adjust the dose.
• Blood-thinning medicines or medicines that prevent blood clotting, including:
• acetylsalicylic acid (ASA - an ingredient in many medicines that lower fever and relieve pain),
• heparin,
• anticoagulant medicines derived from coumarin, such as warfarin or phenprocoumon,
• non-selective anti-inflammatory medicines,
• non-selective phosphodiesterase inhibitors, such as pentoxifylline,
• selective phosphodiesterase 3 inhibitors (PDE 3), such as cilostazol or anagrelide,
• ticlopidine,
• clopidogrel,
• glycoprotein IIb/IIIa antagonists, such as:
• abciximab,
• eptifibatide,
• tirofiban,
• defibrotide. Your doctor will monitor you closely.

Before taking any medicine, ask your doctor or pharmacist, who has more information about the medicines you should use with caution or avoid while taking Iloprost Zentiva.

Taking Iloprost Zentiva with food and drink

It is not expected that food and drink will affect the action of Iloprost Zentiva. However, you should avoid eating or drinking during inhalation.

Pregnancy

• If you have pulmonary hypertension, you should avoid becoming pregnant, as pregnancy can worsen your condition and even threaten your life.
• If you are of childbearing potential, you should use effective contraception from the start of treatment and during treatment.
• If you are pregnant, think you may be pregnant or are planning to have a baby, you should inform your doctor immediately. Iloprost Zentiva can only be used during pregnancy if your doctor decides that the potential benefits outweigh the potential risks to the foetus.

Breast-feeding

It is not known whether Iloprost Zentiva passes into breast milk. It is not recommended to breast-feed while taking Iloprost Zentiva.

Newborns, infants and pregnant women should not be in the same room where the patient is inhaling Iloprost Zentiva.

Driving and using machines

Iloprost Zentiva can lower blood pressure in some patients and may cause dizziness, lightheadedness. You should not drive or operate machinery if you experience these symptoms.

Iloprost Zentiva contains ethanol

This medicine contains 1.5 mg of ethanol (alcohol) per ampoule, which is equivalent to 1.62 mg/ml (96% v/v ethanol). The amount in 1 ml of the medicine is equivalent to less than 1 ml of beer or 1 ml of wine.

3. How to use Iloprost Zentiva

Treatment with Iloprost Zentiva should only be started and monitored by a doctor who has experience in treating pulmonary arterial hypertension.

Dose and duration of treatment

This medicine should always be used exactly as your doctor has told you. If you are not sure, ask your doctor.

• Breelib NebuliserWhen starting treatment with Iloprost Zentiva or switching from another device, the first inhalation should use Iloprost Zentiva 10 micrograms/ml. If the patient tolerates it well, the next dose should be increased to Iloprost Zentiva 20 micrograms/ml. The patient should then continue with this dose.

Most patients perform 6 to 9 inhalationsper day. One inhalation using the Breelib nebuliser usually takes about 3 minutes.

• I-Neb AAD NebuliserThe treatment time with Iloprost Zentiva 10 micrograms/ml was prolonged in the patient, so the doctor decided to switch to Iloprost Zentiva 20 micrograms/ml. Iloprost Zentiva 20 micrograms/ml is twice as concentrated as Iloprost Zentiva 10 micrograms/ml. The active substance may be delivered to the lungs more rapidly. The doctor will monitor the patient's treatment when switching from Iloprost Zentiva 10 micrograms/ml to Iloprost Zentiva 20 micrograms/ml to check if the patient tolerates the higher concentration of the medicine. The dose for one inhalation should be administered 6 to 9 times a day, according to the individual needs and tolerance of the patient. Depending on individual needs, Iloprost Zentiva may be used for long-term treatment.

Patient with kidney or liver disease

• There is no need to adjust the dose in patients with mild or moderate kidney disease (patients with creatinine clearance >30 ml/min).

If you feel that the effect of Iloprost Zentiva is too strong or too weak, you should talk to your doctor or pharmacist.

Method of inhalation

For each inhalation, a new ampoule of Iloprost Zentiva should be used. Just before starting inhalation, the glass ampoule should be broken and the solution poured into the medication chamber using the nebuliser instructions.

• Iloprost Zentiva solution for nebulisation is used with nebulisers prescribed by your doctor (Breelib system, I-Neb AAD).
• The nebuliser turns the Iloprost Zentiva solution into an aerosol that you breathe in through your mouth.
• A mouthpiece should be used for inhalation to prevent Iloprost Zentiva from coming into contact with your skin. Do not use a face mask.
• Follow the instructions provided with the nebuliser. If you are unsure, contact your doctor or pharmacist.
• The remaining Iloprost Zentiva solution in the nebuliser after inhalation should be discarded (see section 5).

Ventilation of the room

The room where Iloprost Zentiva was used should be ventilated or the ventilation should be turned on. Other people may be accidentally exposed to Iloprost Zentiva in the air in the room. In particular, newborns, infants and pregnant women should not be exposed to Iloprost Zentiva. They should not be in the same room where the patient is inhaling Iloprost Zentiva.

• BreelibThe medication chamber should be filled with Iloprost Zentiva immediately before use. When filling the chamber, follow the nebuliser instructions.

• I-Neb AAD
• 1. Immediately before starting inhalation, break and open the glass ampoule of Iloprost Zentiva 20 micrograms/ml containing 1 ml of solution and pour its entire contents into the medication chamber of the nebuliser.
• 2. The pre-set dose in the I-Neb AAD device is controlled by the medication chamber along with the control disk. There are two different medication chambers, each with a different colour. Each medication chamber has control disks of the corresponding colour:
• For Iloprost Zentiva 20 micrograms/ml (5 micrograms dose), the medication chamber with a gold lock and gold control diskis used.
• To ensure that the patient receives the recommended dose, check that the colour of the medication chamber matches the colour of the control disk. They should be the same colour.

Since the I-Neb AAD device can be used for Iloprost Zentiva 10 micrograms/ml and Iloprost Zentiva 20 micrograms/ml, the following table summarises the instructions for using the I-Neb AAD device for the two concentrations of Iloprost Zentiva:

Detailed instructions are provided in the nebuliser user manual; you can also ask your doctor.

Using more than the recommended dose of Iloprost Zentiva

Using more than the recommended dose of Iloprost Zentiva may cause dizziness, headache, sudden flushing of the face, nausea, jaw pain or back pain. The patient may also experience decreased or increased blood pressure, bradycardia (slow heart rate), tachycardia (fast heart rate), vomiting, diarrhoea or limb pain. If any of these symptoms occur after using more than the recommended dose of Iloprost Zentiva, you should:

• stop the inhalation,
• contact your doctor. Your doctor will monitor your condition and treat any symptoms that occur. There is no specific antidote known.

Missing a dose of Iloprost Zentiva

Do not take a double dose to make up for a forgotten dose. Ask your doctor what to do.

Stopping treatment with Iloprost Zentiva

If you want to stop treatment, you should first discuss it with your doctor.

4. Possible side effects

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

The following serious side effectsmay occur. If they do, you should contact your doctor immediately.

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

• cases of bleeding (mostly nosebleeds and coughing up blood from the respiratory system), especially when taking anticoagulant medicines (blood thinners) at the same time. The risk of bleeding may increase in patients who are also taking medicines that prevent platelet aggregation or anticoagulant medicines (see also section 2). Very rare cases of bleeding in the brain (cerebral haemorrhage and intracranial haemorrhage) have been reported, sometimes fatal.

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

• fainting (syncope) is a symptom of the underlying disease, but it may also occur during treatment with Iloprost Zentiva (see section 2 "Warnings and precautions" for advice on how to prevent fainting).
• low blood pressure (hypotension).

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

• bronchospasm and wheezing (see also section 2 "Warnings and precautions").

The following is a list of possible side effects, by frequency:

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

• vasodilation. Symptoms may include flushing or redness of the face
• discomfort in the chest and/or chest pain
• cough
• headache
• nausea
• jaw pain, jaw spasm (trismus)
• peripheral oedema (swelling)

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

• difficulty breathing (dyspnoea)
• dizziness
• vomiting
• diarrhoea
• pain when swallowing (throat irritation and hoarseness)
• throat irritation
• mouth and tongue irritation, including pain
• rash
• fast heart rate (tachycardia)
• awareness of a fast or strong heartbeat (palpitations)

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

• decreased platelet count (thrombocytopenia)
• hypersensitivity (e.g. allergy)
• taste disorders

Other possible symptoms

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

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. How to store Iloprost Zentiva

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 label and on the carton after "EXP". The expiry date refers to the last day of that month.

No special precautions for storage are necessary. Do not freeze.

Any remaining Iloprost Zentiva solution in the nebuliser after inhalation should be discarded.

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

6. Contents of the pack and other information

What Iloprost Zentiva contains

• The active substanceis iloprost. Each 1 ml ampoule contains 20 micrograms of iloprost (as iloprost trometamol).
• The other ingredientsare trometamol, ethanol 96%, sodium chloride, diluted hydrochloric acid (to adjust pH) and water for injections.

What Iloprost Zentiva looks like and contents of the pack

Iloprost Zentiva is a clear, colourless solution without particles, for inhalation use with Breelib and I-Neb nebulisers.

Iloprost Zentiva is provided in a colour-coded glass ampoule (1 ml) containing 1 ml of solution, in a blister pack, in a carton.

Iloprost Zentiva is available in packs of:

30 x 1 ml (6 blisters of 5 ampoules or 5 blisters of 6 ampoules) in a carton

42 x 1 ml (8 blisters of 5 ampoules and 1 blister of 2 ampoules or 7 blisters of 6 ampoules) in a carton

168 x 1 ml (33 blisters of 5 ampoules and 1 blister of 3 ampoules or 28 blisters of 6 ampoules) in a carton

Bulk pack containing 160 ampoules (4 cartons containing 8 blisters of 5 ampoules each).

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Zentiva k.s., U Kabelovny 130, Dolní Mĕcholupy, 102 37 Prague 10, Czech Republic

Manufacturer

Zentiva k.s., U Kabelovny 130, Dolní Mĕcholupy, 102 37 Prague 10, Czech Republic

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Poland, Czech Republic,

Italy

Iloprost Zentiva

Germany

Iloprost Zentiva 20 Mikrogramm/ml Lösung für einen Vernebler

United Kingdom

Iloprost 20 microgram/ml nebuliser solution

For further information about this medicine, please contact the Marketing Authorisation Holder in your country:

Zentiva Polska Sp. z o.o.

ul. Bonifraterska 17

00-203 Warsaw

tel.: +48 22 375 92 00

Date of last revision of the leaflet:February 2023