ILOPROST 10 mcg/ml Solution

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Iloprost Zentiva, 10 micrograms/ml, solution for nebulisation
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Contents of the leaflet
3. What is Iloprost Zentiva and what is it used for
   1. What is Iloprost Zentiva
   2. What is Iloprost Zentiva used for
   3. How does Iloprost Zentiva work
4. Important information before using Iloprost Zentiva
   1. When not to use Iloprost Zentiva
   2. Warnings and precautions
   3. Contact of Iloprost Zentiva with skin or ingestion of Iloprost Zentiva
   4. Children and adolescents
   5. Iloprost Zentiva and other medicines
   6. Using 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. Breelib nebuliser
   3. Method of inhalation
   4. Using a higher than recommended dose of Iloprost Zentiva
   5. Missing a dose of Iloprost Zentiva
   6. Stopping treatment with Iloprost Zentiva
6. Possible side effects
   1. Other possible symptoms
   2. Reporting 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. Germany, Poland, Czech Republic, Italy Iloprost Zentiva United Kingdom (Northern Ireland) Iloprost 10 micrograms/ml
   7. Date of last revision of the leaflet:
   8. Information intended for healthcare professionals only:
   9. Instructions for use and handling of the medicinal product
   10. Device Medicine Dose of iloprost in mouthpiece Estimated inhalation time

Leaflet accompanying the packaging: information for the user

Iloprost Zentiva, 10 micrograms/ml, solution for nebulisation

Iloprostum

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

• 1. What is Iloprost Zentiva and what is it used for
• 2. Important information before using 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 is Iloprost Zentiva and what is it used for

What is Iloprost Zentiva

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

What is Iloprost Zentiva 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 that occurs in the blood vessels between the heart and the lungs. In this disease, the blood pressure in the blood vessels between the heart and the lungs is too high. Iloprost Zentiva is used to improve exercise capacity (ability to perform physical activities) and reduce symptoms of the disease.

How does Iloprost Zentiva work

Inhaling the aerosol produced allows Iloprost Zentiva to reach the lungs, where it can act most effectively on the artery between the heart and the lungs. Better blood flow leads to improved oxygen supply to the body and reduced strain on the heart.

1. Important information before using Iloprost Zentiva

When not to use Iloprost Zentiva

• If you are allergicto iloprost or any of the other ingredients of this medicine (listed in section 6).
• If you are at risk of bleeding- for example, you have an active stomach or duodenal ulcer, or you have had a recent injury, or 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 pectoris). Symptoms may include chest pain.
• heart attack in the last 6 months.
• weakened heart (uncontrolled heart failure), if this condition is not controlled by your doctor.
• severe, unstable heart rhythm.
• heart valve problems (congenital or acquired), which cause the heart to work poorly (not related to pulmonary hypertension).
• If you have had a stroke in the last 3 monthsor any other event that has reduced blood flow to the brain (e.g. transient ischaemic attack).
• If your pulmonary hypertension is caused by a blockage or narrowing 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 breathing difficulties (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.
• 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 lower your blood pressure even further (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, for example 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 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 breathing difficulties, 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. You may need to have the dose of Iloprost Zentiva introduced gradually or your doctor may prescribe a lower dose than usual (see section 3 "How to use Iloprost Zentiva").

Contact of Iloprost Zentiva with skin or ingestion of Iloprost Zentiva

• DO NOT allow the Iloprost Zentiva solution to come into contact with the skin or eyes. If this happens, rinse the skin or eyes immediately with plenty of water.
• DO NOT drink or swallow the Iloprost Zentiva solution. If you accidentally ingest 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 and other medicines

Tell your doctor or pharmacistabout all the medicines you are taking now or have taken recently, as well as any medicines you plan to take. The interaction between Iloprost Zentiva and certain medicines may affect you. You should tell your doctor if you are taking any of the following medicines:

• Medicines used to treat high blood pressure or heart disease, such as:
• beta blockers,
• nitrate medicines that dilate blood vessels,
• angiotensin-converting enzyme (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-steroidal anti-inflammatory medicines,
• 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 abiximab, eptifibatide or tirofiban,
• defibrotide. Your doctor will monitor you closely.

Before taking any medicine, ask your doctor or pharmacist for advice, as they have more information on medicines to be taken with caution or avoided during treatment with Iloprost Zentiva.

Using Iloprost Zentiva with food and drink

No interaction with food and drink is expected. 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 age, 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 be used during pregnancy only 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 breastfeed during treatment with Iloprost Zentiva. Ask your doctor or pharmacist for advice.

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, a feeling of emptiness in the head. You should not drive vehicles, operate machinery or use tools if you experience these symptoms.

Iloprost Zentiva contains ethanol

This medicine contains 0.78 mg of ethanol (alcohol) per ampoule, which is equivalent to 0.81 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. The small amount of alcohol in this medicine does not have noticeable effects.

3. How to use Iloprost Zentiva

Treatment with Iloprost Zentiva should only be started and monitored by a doctor with experience in treating pulmonary 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. The recommended dose of Iloprost Zentiva and the duration of treatment depend on the individual patient's condition. Your doctor will advise you. You should not change the recommended dose without consulting your doctor. Different nebulisers may be used to administer Iloprost Zentiva. Depending on the type of device used and the prescribed dose, 1 ml or 2 ml of Iloprost Zentiva should be used.

Breelib nebuliser

When 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 20 micrograms/ml using another available iloprost-containing medicine. The patient should then continue with this dosing. If the patient does not tolerate the higher dose well, the doctor may decide to reduce the dose and use Iloprost Zentiva 10 micrograms/ml. Most patients perform 6 to 9 inhalationsper day. One inhalation using the Breelib nebuliser usually takes about 3 minutes. The doctor will monitor the treatment after starting the Breelib nebuliser to check if the patient is tolerating the dose and inhalation rate well.

• I-Neb AAD nebuliser

When starting treatment with Iloprost Zentiva, the first dose of inhalation should be 2.5 micrograms of iloprost administered through a mouthpiece. If the patient tolerates it well, the dose should be increased to 5 micrograms of iloprost. The patient should continue with this dosing. If the patient does not tolerate the 5 microgram dose, the dose should be reduced to 2.5 micrograms. Most patients perform 6 to 9 inhalationsper day. One inhalation using the I-Neb AAD nebuliser usually takes about 4 to 10 minutes, depending on the prescribed dose.

• Venta-Neb nebuliser (2 ampoules of Iloprost Zentiva)

When starting treatment with Iloprost Zentiva, the first dose of inhalation should be 2.5 micrograms of iloprost administered through a mouthpiece. If the patient tolerates it well, the dose should be increased to 5 micrograms. The patient should continue with this dosing. If the patient does not tolerate the 5 microgram dose, the dose should be reduced to 2.5 micrograms. Most patients perform 6 to 9 inhalationsper day. One inhalation using the Venta-Neb nebuliser usually takes about 4 to 10 minutes, depending on the prescribed dose. Depending on individual needs, Iloprost Zentiva can be used long-term. Patients with kidney or liver disease do not need to have their dose changed if they have mild or moderate kidney disease (patients with creatinine clearance >30 ml/min). If the patient has severe kidney disease requiring dialysis or liver problems, the doctor will introduce Iloprost Zentiva gradually and may prescribe a lower number of inhalations per day. Treatment should be started with a dose of 2.5 micrograms of iloprost using 1 ampoule of Iloprost Zentiva. Intervals of 3-4 hours should be maintained between doses (corresponding to a maximum of 6 doses per day). Then, the doctor may cautiously shorten the intervals between doses based on the patient's tolerance to the treatment. If the doctor decides to further increase the dose to 5 micrograms, the intervals should be shortened again, starting with 3-4 hours between doses and adjusting based on the patient's tolerance to the treatment.

• 3-4 hour intervals should be maintained between doses and shortened based on the patient's tolerance to the treatment.

If you feel that the effect of Iloprost Zentiva is too strong or too weak, you should discuss this with your doctor or pharmacist. Ask your doctor to help you understand how to use the nebuliser. You should not change the nebuliser without consulting your doctor.

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 of the nebuliser, following the nebuliser's instructions for use. You should strictly follow the instructions provided with the nebuliser, especially those related to hygiene and cleaning the nebuliser. Iloprost Zentiva should always be used as directed by your doctor.

• The Iloprost Zentiva solution for nebulisation is used with nebulisers prescribed by your doctor (Breelib, I-Neb or Venta-Neb system).
• The nebuliser turns the Iloprost Zentiva solution into an aerosol that should be inhaled through the mouth.
• To prevent the Iloprost Zentiva solution from coming into contact with the skin, a mouthpiece should be used for inhalation. Do not use a face mask.
• Follow the instructions provided with the nebuliser. If you have any doubts, contact your doctor or pharmacist again.
• Any 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, following the nebuliser's instructions for use.

• I-Neb AAD
• 1. Immediately before starting inhalation, break and open the glass ampoule containing 1 ml of the solution and pour its entire contents into the medication chamber of the nebuliser.
• 2. The established 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 a dose of 2.5 micrograms, the medication chamber with a red plug and red control diskis used.
• For a dose of 5 micrograms, the medication chamber with a purple plug and purple control diskis used.
• 3. To ensure that the patient receives the prescribed dose, check that the colour of the medication chamber matches the colour of the control disk. They should be the same colour, red for 2.5 micrograms or purple for 5 micrograms.

The table below summarises the instructions for using I-Neb:

• Venta-Neb
• 1. Immediately before starting inhalation, break and open 2 glass ampoules containing 1 ml of the solution each and pour their entire contents into the medication chamber of the nebuliser.
• 2. Two types of programs can be used:
• 3. The doctor will adjust the Venta-Neb to the program according to the prescribed dose.
• P1 Program 1: 5 micrograms of active substance in the mouthpiece; 25 inhalations.
• P2 Program 2: 2.5 micrograms of active substance in the mouthpiece; 10 inhalations.
• 4. To achieve the optimal particle size of Iloprost Zentiva, use the green deflector.

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

Using a higher than recommended dose of Iloprost Zentiva

Using a higher than 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 a higher than 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 missed 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. If you have any further questions about using this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, Iloprost Zentiva can cause side effects, although not everybody gets them. The following serious side effects may occur. If they do, tell your doctor immediately. Very common(may affect more than 1 in 10 people):

• Bleeding (mainly 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). Rarely, fatal cases of bleeding in the brain (cerebral haemorrhage and intracranial haemorrhage) have been reported.

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").
• Low blood pressure (hypotension).

Frequency 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").

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 muscle spasm (trismus)
• peripheral oedema (swelling of the limbs)

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

• breathing difficulties (dyspnoea)
• dizziness
• vomiting
• diarrhoea
• pain when swallowing (throat and larynx irritation)
• throat irritation
• mouth and tongue irritation, including pain
• rash
• rapid heartbeat (tachycardia)
• awareness of rapid or forceful heartbeat (palpitations)

Frequency not known(frequency 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 Zentiva.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorisation holder or its representative in Poland. By reporting side effects, you can help provide more information on the safety of this medicine.

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. There are no special storage instructions. 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 dispose of medicines no longer required. This 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 10 micrograms of iloprost (as iloprost trometamol).
• The other ingredients are: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, I-Neb or Venta-Neb nebulisers. Iloprost Zentiva is supplied in a 1 ml glass ampoule, type I, with a blue ring, containing 1 ml of solution, in a blister pack and a cardboard box. Iloprost Zentiva is available in packs containing: 10 x 1 ml 30 x 1 ml 40 x 1 ml 42 x 1 ml 160 x 1 ml 168 x 1 ml 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:

Germany, Poland, Czech Republic, Italy Iloprost Zentiva United Kingdom (Northern Ireland) Iloprost 10 micrograms/ml

For more detailed information on this medicine, please contact the representative of the marketing authorisation holder in Poland:

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:

Information intended for healthcare professionals only:

Instructions for use and handling of the medicinal product

Patients treated with one type of nebuliser should not change to another type without close medical supervision, as different nebulisers have been shown to produce aerosols with slightly different physical properties and differ in the rate of solution delivery (see section 5.2 of the Summary of Product Characteristics). To minimise unintended exposure, adequate ventilation of the room is recommended. When using the Breelib nebuliser, follow the instructions provided with the device. The medication chamber should be filled with Iloprost Zentiva immediately before use.

Device Medicine Dose of iloprost in mouthpiece Estimated inhalation time

Breelib Iloprost Zentiva 10 micrograms/ml 2.5 micrograms 3 minutes

• I-Neb AADThe I-Neb AAD device is a portable, hand-held nebulisation system with vibrating mesh technology. The system produces droplets using ultrasonic waves, which forces the solution through the mesh. The I-Neb AAD nebuliser has been shown to be suitable for administering Iloprost Zentiva, 10 micrograms/ml. The measured MMAD of the aerosol droplets was 2.1 micrometres. The I-Neb AAD nebuliser monitors the breathing pattern to determine the nebulisation time required to deliver the pre-set dose of 2.5 or 5 micrograms of iloprost.

The dose delivered by the I-Neb AAD device is controlled by the medication chamber, along with the control disk. Each medication chamber has control disks of the corresponding colour: for a dose of 2.5 micrograms, the medication chamber with a red plug and red control diskis used; for a dose of 5 micrograms, the medication chamber with a purple plug and purple control diskis used. Before each inhalation with the I-Neb AAD device, the contents of one 1 ml ampoule of Iloprost Zentiva should be transferred to the medication chamber of the nebuliser. The table below summarises the instructions for using I-Neb:

• Venta-NebIt has been shown that Iloprost Zentiva, 10 micrograms/ml can be administered using the Venta-Neb ultrasonic, battery-powered, portable nebuliser. The measured MMAD of the aerosol droplets was 2.6 micrometres. Before each inhalation with the Venta-Neb device, the contents of two 1 ml ampoules of Iloprost Zentiva should be transferred to the medication chamber of the nebuliser. Two types of programs can be used: P1 Program 1: 5 micrograms of active substance in the mouthpiece; 25 inhalations. P2 Program 2: 2.5 micrograms of active substance in the mouthpiece; 10 inhalations. The doctor will select the established program according to the prescribed dose. The Venta-Neb device visually and audibly signals the start of inhalation. The nebuliser's operation is stopped after delivering the set dose. To achieve the optimal particle size of Iloprost Zentiva, use the green deflector. Detailed instructions are provided in the Venta-Neb nebuliser user manual.

  Device	Dose of iloprost in mouthpiece	Estimated inhalation time
  Venta-Neb	2.5 micrograms 5 micrograms	4 min 8 min

  The efficacy and safety of iloprost inhalation using other nebulisation systems with different characteristics of iloprost solution nebulisation have not been established.