ILOPROST ZENTIVA 10 micrograms/ml SOLUTION FOR NEBULIZER INHALATION

Introduction

Package Leaflet: Information for the User

Iloprost Zentiva 10 micrograms/ml solution for inhalation by nebuliser

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

• Keep this leaflet.You may need to read it again.
• If you have any further questions,ask your doctor, pharmacist or nurse.
• 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

1. What is Iloprost Zentiva and what is it used for
2. What you need to know before you use Iloprost Zentiva
3. How to use Iloprost Zentiva
4. Possible side effects
5. Storing 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. Iloprost mimics a natural substance in the body called prostacyclin. This medicine prevents unwanted blockage or narrowing of blood vessels and allows more blood to flow through the blood vessels.

What Iloprost Zentiva is used for

This medicine is used to treat moderate cases of primary pulmonary hypertension (PPH) in adult patients. PPH is a type of pulmonary hypertension where the cause of the high blood pressure is unknown.

This is a disease where blood pressure is too high in the blood vessels between the heart and lungs.

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

How Iloprost Zentiva works

When inhaled, the aerosol delivers iloprost to the lungs, where it works most effectively in the artery between the heart and lungs. By improving blood flow, oxygen supply to the body is improved and the strain on the heart is reduced.

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

Do not use this medicine

• to iloprost or any of the other ingredients of this medicine (listed in section 6),
• – for example, if you have an active stomach or duodenal ulcer, if you have had a physical injury (trauma), if you are at risk of intracranial bleeding,

• , such as:

• poor blood flow to the heart muscle (severe coronary artery disease or unstable angina). Symptoms can include chest pain,
• a heart attack in the last 6 months,
• weak heart (decompensated heart failure) that is not under close medical supervision,
• severe heart rhythm disorders,
• a heart valve defect (congenital or acquired) that makes the heart not work properly (not related to pulmonary hypertension),

• or any other event that has reduced blood flow to the brain (e.g. transient ischaemic attack),
• (veno-occlusive disease).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before starting this medicine:

• Inhaling iloprost may trigger breathing difficulties (see section 4), especially in patients with bronchospasm (a sudden narrowing of the muscle of the small airways) and wheezing. Tell your doctor if you have a lung infection, severe asthma or other chronic lung disease(chronic obstructive pulmonary 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) you should not start therapy with this medicine.
• In general, you will need to be careful to avoid the effects of low blood pressure, such as fainting and dizziness:

• Tell your doctor if you are taking other medicines, as the combination with iloprost may lower your blood pressure even further (see "Using Iloprost Zentiva with other medicines" below).
• 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 episodes, avoid any exceptional effort, for example during physical exercise; it may be helpful to inhale iloprost before doing so. Fainting episodes may be due to the underlying disease. Tell your doctor if they get worse, 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 yourcondition is getting worse, tell your doctor. Symptoms can include swelling of feet and ankles, difficulty breathing, palpitations, need to urinate more frequently at night or oedema. Your doctor will consider whether you need to change your treatment.
• If you have difficulty breathing, cough up blood and/or sweat excessively, these may be signs that you have fluid in your lungs(pulmonary oedema). Stop using this medicine and tell your doctor immediately. He/she will look for the cause and take appropriate measures.
• If you have liver or severe kidney problems that require dialysis, tell your doctor. You may need to be gradually switched to the prescribed dose or your doctor may prescribe a lower dose of iloprost than for other patients (see section 3 "How to use Iloprost Zentiva").

Contact of iloprost with skin or ingestion of iloprost

• Do not let the iloprost solution come into contact with your skin or eyes. If this happens, wash the skin or eyes immediately with plenty of water.
• Do not drink or swallow the iloprost solution. If this happens accidentally, drink plenty of water and tell your doctor.

Children and adolescents

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

Other medicines and Iloprost Zentiva

Tell your doctor or pharmacist if you areusing, have recently used or might use any other medicines. Iloprost may affect how other medicines work and vice versa.

Tell your doctor if you are taking:

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• Beta-blockers.
• Vasodilators of the nitrate type.
• ACE inhibitors.

Your blood pressure may drop too low. Your doctor may need to change your dose.

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• Acetylsalicylic acid (AAS, a compound found in many medicines that reduces fever and relieves pain).
• Heparin.
• Anticoagulants of the coumarin type, such as warfarin or phenprocoumon.
• Non-steroidal anti-inflammatory drugs.
• Non-selective phosphodiesterase inhibitors, such as pentoxifylline.
• Selective phosphodiesterase 3 (PDE 3) inhibitors, such as cilostazol or anagrelide.
• Ticlopidine.
• Clopidogrel.
• Glycoprotein IIb/IIIa antagonists, such as:
• • Abciximab.
  • Eptifibatide.
  • Tirofiban.
  • Defibrotide.

Your doctor will keep you under close supervision.

Before taking any medicine, talk to your doctor or pharmacist, who has more information on medicines that you should be cautious with or avoid when using this medicine.

Using Iloprost Zentiva with food and drinks

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

Pregnancy

• If you have pulmonary hypertension,avoid becoming pregnant, as pregnancy can worsen your disease and even put your life at risk.
• If you could become pregnant, use reliable contraceptives from the start of treatment and during treatment.
• If you are pregnant, think you may be pregnant or plan to become pregnant, tell your doctor immediately. This medicine should only be used during pregnancy if your doctor decides that the potential benefit outweighs the potential risks to you and your baby.

Breast-feeding

It is not known whether this medicine passes into breast milk. The potential risk to breast-fed infants cannot be excluded and breast-feeding should be avoided during treatment with iloprost.

Talk to your doctor or pharmacist before using any medicine.

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

Driving and using machines

This medicine can lower your blood pressure and may cause dizziness or instability in some people. Do not drive or use tools or machines if you notice these effects.

Iloprost Zentiva contains ethanol

Iloprost Zentiva 10 micrograms/ml contains 0.75 mg of alcohol (ethanol) in 1 ml of solution for inhalation by nebuliser, which is equivalent to 0.81 mg of ethanol 96 % (v/v).

The amount of alcohol in 1 ml of this 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 produce any noticeable effect.

3. How to use Iloprost Zentiva

Treatment with iloprost should only be started by a doctor with experience in the treatment of pulmonary hypertension.

How much to inhale and for how long

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, talk to your doctor again.

The dose of iloprost you need and the duration of treatment you need depend on your condition. Your doctor will advise you. Do not change the recommended dose without talking to your doctor.

Different nebuliser devices can be used to administer iloprost 10 micrograms/ml.

Depending on the type of device used and the prescribed dose, it is suitable to use 1 ml or 2 ml of Iloprost Zentiva 10 micrograms/ml.

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When starting treatment with iloprost or switching from an alternative device, the first inhalation should be with iloprost 10 micrograms/ml. If you tolerate this dose well, your next inhalation will be with iloprost 20 micrograms/ml. You should continue with this dose.

If you cannot tolerate the inhalation of iloprost 20 micrograms/ml, talk to your doctor, who may decide that you should receive iloprost 10 micrograms/ml.

Most people will need to have 6 to 9 inhalation sessionsspread throughout the day. The duration of each inhalation session with Breelib is usually 3 minutes.

Your doctor will supervise your treatment when you start using the Breelib nebuliser to ensure that you tolerate the dose and inhalation rate well.

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When starting treatment with iloprost, the first inhaled dose should be 2.5 micrograms of iloprost delivered by the nebuliser 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 dose of 5 micrograms, the dose should be reduced to 2.5 micrograms.

Most people will need to have 6 to 9 inhalation sessionsspread throughout the day. The duration of each inhalation session with I-Neb AAD is usually 4 to 10 minutes, depending on the prescribed dose.

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When starting treatment with iloprost, the first inhaled dose should be 2.5 micrograms of iloprost delivered by the nebuliser 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 dose of 5 micrograms, the dose should be reduced to 2.5 micrograms.

Most people will need to have 6 to 9 inhalation sessionsspread throughout the day. The duration of each inhalation session with Venta-Neb is usually 4 to 10 minutes, depending on the prescribed dose.

This medicine can be used for long-term treatment, depending on your individual needs.

If you have kidney or liver problems

No dose adjustment is necessary in patients with mild or moderate kidney problems (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 iloprost gradually and may prescribe fewer inhalations per day. Start treatment by inhaling 2.5 micrograms of iloprost, using a 1 ml ampoule of iloprost 10 micrograms/ml. Use dosing intervals of 3 – 4 hours (which corresponds to a maximum of 6 administrations per day). Your doctor may then cautiously shorten the dosing intervals based on how well you tolerate the treatment. If your doctor decides to increase the dose further to 5 micrograms, the dosing intervals should be set to 3 – 4 hours again and shortened based on how well you tolerate the treatment.

If you notice that the effect of this medicine is too strong or too weak, talk to your doctor orpharmacist. Ask your doctor to have someone help you get used to using the nebuliser. You should not switch to another nebuliser without talking to the doctor who is treating you.

How to inhale

For each inhalation session, use a new ampoule of iloprost. Just before starting to inhale, break the glass ampoule and pour the solution into the nebuliser medication chamber, following the instructions for use of the nebuliser.

Follow the instructions that come with the nebuliser carefully, especially those relating to hygiene and cleaning of the nebuliser.

Follow the instructions for administration of this medicine exactly as told by your doctor.

• Iloprost Zentiva 10 micrograms/ml solution for inhalation by nebuliser is inhaled using the nebulisers that your doctor has prescribed (Breelib, Venta-Neb or I-Neb AAD).
• The nebuliser turns the iloprost solution into an aerosol that is inhaled through the mouth.
• For inhalation, use a mouthpiece to avoid iloprost coming into contact with your skin. Do not use a mask.
• Follow the instructions that come with the nebuliser carefully. Talk to your doctor or pharmacist if you are unsure.
• Any remaining iloprost solution in the nebuliser after inhalation should be discarded (see section 5).

Ventilation of the room

Make sure to ventilate or air the room where you have taken the iloprost treatment. Other people may be accidentally exposed to iloprost through the air in the room. In particular, newborns, infants and pregnant women should not be in the same room while you are inhaling iloprost.

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Fill the medication chamber with iloprost immediately before use. Follow the instructions for use of the nebuliser regarding filling.

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1. Immediately before starting to inhale, break the glass ampoule containing 1 ml of solution, and pour all of its contents into the nebuliser medication chamber.
2. The pre-set dose administered by the I-Neb AAD system is controlled by the medication chamber, in combination with a control disc. There are two medication chambers with different coloured codes. For each medication chamber, there is a control disc with a corresponding coloured code:
   • For the 2.5 microgram dose, the medication chamber with the red latch is used together with the red control disc.
   • For the 5 microgram dose, the medication chamber with the purple latch is used together with the purple control disc.
3. To ensure that you receive the prescribed dose, check the colour of the medication chamber and the colour of the control disc. These should be the same, 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 use of the I-Neb:

Instructions for Use

1. Immediately before inhalation, break two glass ampoules containing 1 ml of solution, and pour all their contents into the medication chamber of the nebulizer.
2. Two programs can be used:
3. Your doctor will adjust the Venta-Neb system program to your needs so that you receive the prescribed dose for you.
   • P1 Program 1: 5 micrograms of active ingredient in the mouthpiece, 25 inhalation cycles.
   • P2 Program 2: 2.5 micrograms of active ingredient in the mouthpiece, 10 inhalation cycles.
4. To obtain the optimal drop size for the administration of this medication, the green deflector plate must be used.

For more details, consult the nebulizer device's instruction manual or consult your doctor.

If you use more Iloprost Zentiva than you should

Using more iloprost than you should may cause dizziness, headache, flushing (redness of the face), nausea (feeling of discomfort), jaw pain 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 iloprost than you should:

• Interrupt the inhalation session.
• Consult your doctor.

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to use Iloprost Zentiva

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

If you interrupt treatment with Iloprost Zentiva

If you interrupt or wish to interrupt treatment, first consult your doctor.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone may experience them.

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

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

• Bleeding episodes (mostly nosebleeds and coughing up blood) may occur very frequently, especially if you are taking treatment to thin the 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, including cerebral and intracranial hemorrhage.

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

• Fainting (syncope) is a symptom of the disease itself, but it may also appear during treatment with iloprost (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 muscle of the small airways) and wheezing (see also section 2 "Warnings and precautions").

The following is a list of other possible side effects based on their likelihood 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 / spasm of the jaw muscles (trismus).
• Swelling of the limbs (peripheral edema).

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

• Difficulty breathing (dyspnea).
• Dizziness.
• Vomiting.
• Diarrhea.
• Pain when swallowing (pharyngolaryngeal irritation).
• Throat irritation.
• Irritation in the mouth and tongue, including pain.
• Rash.
• Fast heartbeat (tachycardia).
• Awareness of fast or intense heartbeat (palpitations).

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

• Decrease in the number of platelets in the blood (thrombocytopenia).
• Hypersensitivity (i.e., allergy).
• Taste disorders (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 disease itself, but it may also occur during treatment with Iloprost Zentiva.

Reporting of side effects

If you experience any side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Iloprost Zentiva

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the label and carton after CAD. The expiration date refers to the last day of that month.

No special storage conditions are required. Do not freeze.

Any remaining Iloprost Zentiva solution in the nebulizer after inhalation must be discarded.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Contents of the pack and further information

Composition of Iloprost Zentiva

• The active ingredientis iloprost.

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

• The other ingredients aretrometamol, ethanol 96%, sodium chloride, hydrochloric acid (for pH adjustment), and water for injectable preparations.

Appearance and packaging of the product

Iloprost Zentiva is a clear and colorless solution without visible particles for inhalation with the Breelib, I-Neb, or Venta-Neb nebulizers

Iloprost Zentiva 10 micrograms/ml is supplied in a transparent glass ampoule of hydrolytic class I with a blue identification ring, containing 1.0 ml of solution, packaged in a blister pack and cardboard box.

Iloprost Zentiva 10 micrograms/ml is available in the following packs:

10x1 ml (2 blisters with 5 ampoules), 30x1 ml (6 blisters with 5 ampoules or 5 blisters with 6 ampoules), 40x1 ml (8 blisters with 5 ampoules), 42x1 ml (8 blisters with 5 ampoules and 1 blister with 2 ampoules or 7 blisters with 6 ampoules), 168x1 ml (33 blisters with 5 ampoules and 1 blister with 3 ampoules or 28 blisters with 6 ampoules), multiple pack containing 160 ampoules (4 inner boxes containing 8 blisters with 5 ampoules).

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer:

Zentiva k.s.

U Kabelovny 130

Dolní Mecholupy

102 37 Prague 10

Czech Republic

For further information about this medication, please contact the local representative of the marketing authorization holder: Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

This medication is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet:06/2021

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/.

This information is intended only for healthcare professionals:

Instructions for use and handling

Patients stabilized with a nebulizer should not switch to another nebulizer without close supervision by the treating physician, as it has been shown that different nebulizers produce aerosols with slightly different physical characteristics and may have a faster administration of the solution (see section 5.2 of the Summary of Product Characteristics).

To minimize accidental exposure, it is recommended to keep the room well ventilated.

If the Breelib nebulizer is used, the instructions for use accompanying the device must be followed.

Fill the medication chamber with Iloprost Zentiva immediately before use.

The I-Neb AAD system is a portable, manual, and vibrational mesh nebulizer system. This system generates small droplets by ultrasonics, which makes the solution pass through a mesh. It has been shown that the I-Neb AAD nebulizer is suitable for the administration of Iloprost Zentiva 10 micrograms/ml.

The measured MMAD of the small aerosol droplets was 2.1 micrometers.

This nebulizer controls the breathing pattern to determine the required inhalation time to administer the pre-set dose of 2.5 or 5 micrograms of iloprost.

The dose administered by the I-Neb AAD system is controlled by the medication chamber, in combination with a control disk. Each medication chamber has a color code and has a control disk with its corresponding color code.

• For a dose of 2.5 micrograms, the medication chamber with the red latch is used with the red control disk.
• For a dose of 5 micrograms, the medication chamber with the purple latch is used with the purple control disk.

In each I-Neb AAD inhalation session, immediately before use, the contents of one 1 ml ampoule of Iloprost Zentiva will be poured into the medication chamber.

The following table includes a summary of the instructions for the use of the I-Neb for Iloprost Zentiva:

Venta-Neb, a portable ultrasonic nebulizer with a battery, has also been shown to be suitable for the administration of Iloprost Zentiva 10 micrograms/ml. The measured MMAD of the aerosol droplets was 2.6 micrometers. In each inhalation session, the contents of two ampoules containing 1 ml of Iloprost Zentiva 10 micrograms/ml solution for nebulization will be poured into the medication chamber of the nebulizer immediately before use.

Two programs can be used:

• P1 Program 1: 5 micrograms of active ingredient in the mouthpiece, 25 inhalation cycles.
• P2 Program 2: 2.5 micrograms of active ingredient in the mouthpiece, 10 inhalation cycles. The doctor selects the pre-set program.

An optical and acoustic signal from the Venta-Neb system alerts the patient to inhale. It stops automatically after applying the pre-set dose. To obtain the optimal drop size for the administration of Iloprost Zentiva, the green deflector plate must be used. Consult the details in the Venta-Neb nebulizer instruction manual.

The efficacy and tolerability of inhaled iloprost have not been established when administered with other nebulization systems that provide different characteristics of iloprost solution nebulization.