Iloprost Zentiva

Package leaflet: Information for the user

Iloprost Zentiva 10 micrograms/ml solution for nebulisation

Generic medicine
Please 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Iloprost Zentiva is and what it is used for
2. What you need to know 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 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 natural substance called
prostacyclin. Iloprost Zentiva prevents unwanted blockage or constriction of blood vessels and allows a greater amount of blood to flow through the vessels.
What Iloprost Zentiva is used for
Iloprost Zentiva is used to treat adult patients with moderate primary pulmonary hypertension (PPH). PPH is a type of pulmonary hypertension in which the cause of increased blood pressure is unknown.
This is a condition in which the blood pressure in the vessels carrying blood between the heart and the lungs is too high.
Iloprost Zentiva is used to improve exercise capacity (ability to perform physical activity) and symptoms.
How Iloprost Zentiva works
By inhaling the nebulized solution, Iloprost Zentiva is delivered directly to the lungs, where it acts most effectively on the artery between the heart and the lungs. Improving blood flow enhances oxygen delivery to the body and reduces the workload on the heart.

2. What you need to know before using Iloprost Zentiva

Do not use Iloprost Zentiva

• if you are allergic to iloprost or to any of the other ingredients of this medicine (listed in section 6).
• if you are at risk of bleeding – for example, if you have an active stomach or duodenal ulcer, if you have sustained a physical injury (trauma), or if you are at risk of intracranial bleeding.
• if you have had heart problems, such as:
  • inadequate blood supply to the heart (severe coronary artery disease or unstable angina). Symptoms may include chest pain.
  • a heart attack within the last six months.
• heart failure (cardiac decompensation) that is not under close medical supervision.
• markedly unstable heart rate.
• a heart valve defect (congenital or acquired) causing heart failure (unrelated to pulmonary hypertension).
  • if you have had a stroke within the last 3 months or any other event that reduced blood flow to the brain (e.g. transient ischemic attack).
  • if your pulmonary hypertension is caused by blockage or narrowing of the pulmonary veins (pulmonary veno-occlusive disease).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Iloprost Zentiva:

• 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. Inform your doctor if you have a lung infection, severe asthma, or chronic lung diseases (chronic obstructive pulmonary disease). Your doctor will monitor you closely.
• Your blood pressure will be measured before treatment begins; if it is too low (less than 85 mmHg systolic), treatment with Iloprost Zentiva should not be started.
• In general, you should be particularly careful to avoid effects of low blood pressure such as fainting and dizziness:
  • Inform your doctor if you are taking any other medicines, as their combined effects with Iloprost Zentiva may further lower your blood pressure (see below “Other medicines and Iloprost Zentiva”).
  • Rise 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 while still lying down.
  • If you are prone to fainting, avoid excessive exertion, such as during physical exercise; inhaling Iloprost Zentiva before exercise may be helpful. Episodes of fainting may be due to your underlying disease. Inform your doctor if these episodes worsen. A dose adjustment or change in therapy may be considered.
• If you have heart failure, such as right-sided heart failure, and feel that your condition is worsening, discuss this with your doctor. Symptoms of worsening may include swelling of the feet and ankles, shortness of breath, palpitations, frequent need to urinate at night, or edema. Your doctor will assess whether your therapy should be changed.
• If you experience difficulty breathing, coughing up blood and/or excessive sweating, these may be signs that you have fluid in your lungs (pulmonary edema). Stop treatment with Iloprost Zentiva and contact your doctor immediately. Your doctor will determine the cause of your symptoms and take appropriate measures.
• If you have liver problems or severe kidney problems requiring dialysis, discuss this with your doctor. You may be prescribed a lower or gradually adjusted dose of Iloprost Zentiva compared to other patients (see section 3 “How to use Iloprost Zentiva”).

Contact with skin or accidental ingestion of Iloprost Zentiva

• DO NOT allow the Iloprost Zentiva solution to come into contact with your skin or eyes. If this occurs, rinse the affected 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 inform your doctor.

Children and adolescents
The safety and efficacy have not been established in children and adolescents under 18 years of age.
Other medicines and Iloprost Zentiva
Tell your doctor or pharmacist if you are using, have recently used, or might use any other
medicines. Iloprost Zentiva and certain other medicines may interact and affect each other’s action
in the body. Inform your doctor if you are taking:

• Medicines used to treat high blood pressure or heart conditions, such as
  • beta-blockers,
  • nitro-vasodilators,
  • ACE inhibitors. Your blood pressure may drop too much. Your doctor may adjust the dosage.
• Medicines that thin the blood or inhibit blood clotting, including
  • acetylsalicylic acid (ASA – a substance found in many medicines that reduce fever and relieve pain),
  • heparin,
  • coumarin anticoagulants, 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 monitor you closely.
Before taking any medicine, consult your doctor or pharmacist, who can provide further information about medicines that require caution or should be avoided when using Iloprost Zentiva.
Iloprost Zentiva with food and drink
Food and drink should not affect Iloprost Zentiva. However, you should avoid eating or drinking during inhalation.
Pregnancy

• If you have pulmonary hypertension, avoid pregnancy, as it may worsen your condition and endanger your life.
• If you could become pregnant, use reliable contraception from the start of treatment and throughout its duration.
• If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor immediately before taking this medicine. Iloprost Zentiva should be used during pregnancy only if your doctor decides that the potential benefit outweighs the potential risk to you and the fetus.

Breast-feeding
It is not known whether Iloprost Zentiva passes into breast milk. A potential risk to breastfed infants cannot be ruled out; therefore, breast-feeding should be avoided during treatment with Iloprost Zentiva.
Consult your doctor or pharmacist before taking any medicine.
Newborns, children, and pregnant women must not be present in the same room while you are inhaling
Iloprost Zentiva.
Driving and using machines
Iloprost Zentiva lowers blood pressure and may cause dizziness or lack of concentration in some people.
Do not drive or operate machinery if you experience these effects.
Iloprost Zentiva contains ethanol
This medicine contains 0.78 mg of alcohol (ethanol) per vial, equivalent to 0.81 mg of 96% ethanol (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 amounts of alcohol in this medicine have no significant effects.

3. How to use Iloprost Zentiva

Iloprost Zentiva therapy must be initiated exclusively by a physician experienced in the treatment of pulmonary hypertension.

How much Iloprost Zentiva to inhale and for how long

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.

The appropriate dose of Iloprost Zentiva and the duration of treatment depend on your individual condition. Your doctor will advise you accordingly. Do not change the recommended dose without first consulting your doctor.

Different nebulizing devices can 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 10 micrograms/ml may be appropriate.

• Breelib nebulizer If you are starting treatment with Iloprost Zentiva or have previously used a different device, the first inhalation should be performed with Iloprost Zentiva 10 micrograms/ml. If you tolerate this dose well, the next inhalation should be increased using another commercially available formulation containing 20 micrograms/ml of iloprost. You should continue with this dose. If you do not tolerate inhalation with this higher dose, consult your doctor, who may prescribe Iloprost Zentiva 10 micrograms/ml. Most people will have 6 to 9 inhalation sessions spread throughout the day. The duration of each session with Breelib is generally about 3 minutes. When you begin using the Breelib nebulizer, your doctor will supervise your treatment to ensure you tolerate both the dose and the inhalation rate.

• I-Neb AAD nebulizer Generally, at the start of treatment with Iloprost Zentiva, the first inhaled dose should correspond to 2.5 micrograms of iloprost delivered at the mouthpiece. If you tolerate this dose well, the dose should be increased to 5 micrograms of iloprost and maintained at this level. If you do not tolerate the 5 microgram dose, it should be reduced to 2.5 micrograms. Most people will have 6 to 9 inhalation sessions spread throughout the day. The duration of each session with I-Neb AAD ranges between 4 and 10 minutes, depending on the prescribed dose.

• Venta-Neb nebulizer (2 vials of Iloprost Zentiva) Generally, at the start of treatment with Iloprost Zentiva, the first inhaled dose should correspond to 2.5 micrograms of iloprost delivered at the mouthpiece. If you tolerate this dose well, the dose should be increased to 5 micrograms of iloprost and maintained at this level. If you do not tolerate the 5 microgram dose, it should be reduced to 2.5 micrograms.

Most people will have 6 to 9 inhalation sessions spread throughout the day. The duration of each inhalation session with Venta-Neb ranges between 4 and 10 minutes, depending on the prescribed dose.

Depending on individual needs, Iloprost Zentiva may be used for long-term treatment.

If you have kidney or liver problems

In patients with mild or moderate renal impairment (patients with creatinine clearance >30 ml/min), dose adjustment is not necessary.

In cases of severe renal impairment requiring dialysis or in patients with liver disease, your doctor will initiate Iloprost Zentiva therapy gradually and may prescribe fewer inhalations per day.

Begin therapy with the inhalation of 2.5 micrograms of iloprost using one 1 ml vial of Iloprost Zentiva. Allow intervals of 3–4 hours between inhalations (this corresponds to a maximum of 6 administrations per day). Subsequently, your doctor may cautiously reduce the dosing intervals, depending on your tolerance to treatment.

If your doctor decides to increase the dose up to a maximum of 5 micrograms, intervals of 3–4 hours should initially be maintained again, which may then be reduced depending on your treatment tolerance.

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

Ask your doctor to have someone assist you in becoming familiar with the use of the nebulizer. Do not switch to another type of nebulizer without consulting your treating doctor.

How to perform the inhalation

For each inhalation session, a new vial of Iloprost Zentiva must be used. Immediately before starting inhalation, break open the glass vial and pour the solution into the nebulizer chamber, following the nebulizer’s instructions for use.

Strictly follow all instructions provided with the device, particularly those relating to hygiene and cleaning of the nebulizer.

Take Iloprost Zentiva exactly as instructed by your doctor.

• The Iloprost Zentiva 10 micrograms/ml nebulizing solution must be inhaled through the nebulizers prescribed by your doctor (either the Breelib system, Venta-Neb system, or the I-Neb AAD system).
• The nebulizer converts the Iloprost Zentiva solution into an aerosol, which you inhale through your mouth.
• For inhalation, you must use a mouthpiece to prevent Iloprost Zentiva from coming into contact with your skin. Do not use a face mask.
• Carefully follow all instructions provided by the manufacturer for the delivery device. Consult your doctor or pharmacist if you have any doubts.
• Any residual solution of Iloprost Zentiva remaining in the nebulizer after inhalation must be discarded (see section 5).

Room ventilation

Ensure that the room where you inhale Iloprost Zentiva is well ventilated or aired out. Other people could accidentally inhale Iloprost Zentiva through the room air. In particular, newborns, children, and pregnant women must not be present in the same room while you are inhaling Iloprost Zentiva.

• Breelib: Pour Iloprost Zentiva into the nebulizer chamber immediately before use, following the nebulizer’s instructions for use.

• I-Neb AAD
  1. Immediately before inhaling, break the glass vial containing 1 ml of solution, and pour the entire contents into the nebulizer chamber.
  2. The preset dose delivered by the I-Neb AAD system is controlled by the nebulizer chamber in combination with a control disc. There are two nebulizer chambers, each distinguished by a different color. Each nebulizer chamber corresponds to a colored control disc:
     • To deliver a dose of 2.5 micrograms, use the nebulizer chamber with the red safety lock together with the red control disc.
     • To deliver a dose of 5 micrograms, use the nebulizer chamber with the purple safety lock together with the purple control disc.
  3. To ensure you receive the prescribed dose, check the color of the nebulizer chamber and control disc. They must be the same color—red for the 2.5 microgram dose or purple for the 5 microgram dose.

The following table provides a summary of the instructions for use of I-Neb:

• Venta-Neb
  1. Immediately before starting inhalation, break 2 glass vials, each containing 1 ml of solution, and pour the entire contents into the nebulizer chamber.
  2. You can choose between two programs:
  3. Your doctor will adjust Venta-Neb to the program you need to receive the prescribed dose.
• P1 Program 1: 5 micrograms of active substance over 25 inhalation cycles via mouthpiece.
• P2 Program 2: 2.5 micrograms of active substance over 10 inhalation cycles via mouthpiece. 4. Use the green deflector to obtain droplets of optimal size for the administration of Iloprost Zentiva.

For further details, please read the nebuliser's instruction manual or consult your doctor.
If you use more Iloprost Zentiva than you should
Using more Iloprost Zentiva than prescribed may cause dizziness, headache, flushing (reddening of the face), nausea (feeling unwell), jaw or back pain.
You may also experience an increase or decrease in blood pressure, bradycardia (slowing of the heartbeat), tachycardia (acceleration of the heartbeat), vomiting, diarrhoea, or pain in the limbs. If you experience any of these symptoms after having used more Iloprost Zentiva than you should have, you must:

• stop the inhalation session immediately;
• consult your doctor.

Your doctor will monitor and treat any symptoms you may have. There is no known specific antidote.
If you forget to use Iloprost Zentiva
Do not take a double dose to make up for a forgotten dose. Consult your doctor, who will advise you what to do.
If you stop using Iloprost Zentiva
If you stop or wish to stop treatment, consult your doctor first.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following serious side effects may occur. In this case, consult your doctor immediately.
Very common (may affect more than 1 in 10 people):

• bleeding events (especially nosebleeds (epistaxis) and coughing up blood (haemoptysis)) may occur very commonly, particularly if you are also taking blood-thinning medicines (anticoagulants). The risk of bleeding may increase in patients receiving antiplatelet agents or anticoagulants concomitantly (see also section 2). Fatal cases have been reported very rarely, including cases of bleeding in the brain (cerebral and intracranial haemorrhage).

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

• fainting (syncope) is a symptom of your disease but may also occur during treatment with Iloprost Zentiva (see also section 2 “Warnings and precautions” for advice on how to avoid it).
• reduction in blood pressure (hypotension).

Frequency not known (frequency 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 side effects are listed below in order of frequency:
Very common (may affect more than 1 in 10 people):

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

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

• breathing difficulties (dyspnoea)
• dizziness
• vomiting
• diarrhoea
• pain on swallowing (pharyngolaryngeal irritation)
• throat irritation
• irritation of the mouth and tongue, accompanied by pain
• skin rashes
• rapid heartbeat (tachycardia)
• awareness of a fast or forceful heartbeat (palpitations).

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

• decrease in the number of platelets in the blood (thrombocytopenia)
• hypersensitivity (e.g. allergy)
• taste disturbances (dysgeusia).

Other possible side effects

• Swelling, particularly in the ankles and legs, due to fluid retention (peripheral oedema) is a very common symptom of the disease itself but may also occur during treatment with Iloprost Zentiva.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . 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 vial and the carton after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions. Do not freeze.
Any Iloprost Zentiva solution remaining in the nebulizer after inhalation must be discarded.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Iloprost Zentiva contains

• The active substance is iloprost. Each 1 ml vial contains 10 micrograms of iloprost (as iloprost trometamol).
• The other components are trometamol, ethanol 96%, sodium chloride, hydrochloric acid for pH adjustment, and water for injections.

Description of the appearance of Iloprost Zentiva and contents of the pack
Iloprost Zentiva is a clear, colourless solution free from visible particles, for inhalation via a nebuliser,
Breelib, I-Neb or Venta-Neb. Iloprost Zentiva is supplied in a clear glass vial (hydrolytic class I) with a blue identification ring, containing 1.0 ml of solution, packaged in blisters and cardboard boxes.
Iloprost Zentiva is available in the following pack sizes:
10 x 1 ml (2 blisters with 5 vials)
30 x 1 ml (6 blisters with 5 vials or 5 blisters with 6 vials)
40 x 1 ml (8 blisters with 5 vials)
42 x 1 ml (8 blisters with 5 vials and 1 blister with 2 vials or 7 blisters with 6 vials)
168 x 1 ml (33 blisters with 5 vials and 1 blister with 3 vials or 28 blisters with 6 vials)
Multiple pack containing 160 vials (4 inner boxes containing 8 blisters with 5 vials each)
Not all pack sizes may be marketed.
Marketing Authorisation Holder:
Zentiva Italia S.r.l.
Via P. Paleocapa 7 – 20121 Milan
Italy
Manufacturer:
Zentiva, k.s.
U Kabelovny 130, Prague 10-Dolní Měcholupy, 102 37
Czech Republic
This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland)
with the following names:
Czech Republic, Poland, Germany, Italy: Iloprost Zentiva
United Kingdom (Northern Ireland): Iloprost Zentiva 10 microgram/ml

The following information is intended exclusively for healthcare professionals:

Instructions for use and handling

Stable patients using one type of nebulizer must not switch to another nebulizer without close supervision by their physician, as different nebulizers produce an aerosol with slightly different physical characteristics and may deliver the solution more rapidly (see section 5.2 of the Summary of Product Characteristics).
To minimize accidental exposure, it is recommended to ensure adequate ventilation in the environment.

• Breelib For use of the Breelib nebulizer, follow the instructions for use provided with the device. Pour Iloprost Zentiva into the nebulizer chamber immediately before use.

• I-Neb AAD The I-Neb AAD System is a portable, handheld nebulizer based on vibrating mesh technology. This system uses ultrasound to push the solution through a mesh to generate droplets. The I-Neb AAD nebulizer has been shown to be suitable for the administration of Iloprost Zentiva. The mass median aerodynamic diameter (MMAD) of the aerosol droplets was 2.1 micrometers. This nebulizer monitors the breathing pattern to determine the aerosol release intervals required to deliver the preset dose of 2.5 or 5 micrograms of iloprost. The delivered dose from the I-Neb AAD system is controlled by the nebulizer chamber in combination with a control disc. Each nebulizer chamber is color-coded and corresponds to a colored control disc:
  • To deliver a dose of 2.5 micrograms, use the nebulizer chamber with the red safety lock together with the red control disc.
  • To deliver a dose of 5 micrograms, use the nebulizer chamber with the purple safety lock together with the purple control disc. For each inhalation session with I-Neb AAD, transfer the contents of one 1 ml vial of Iloprost Zentiva into the nebulizer chamber immediately before use.

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

• Venta-Neb Venta-Neb, a portable, battery-powered ultrasonic nebulizer, has also proven suitable for the administration of Iloprost Zentiva 10 mcg/ml. The measured MMAD value of the aerosol droplets is 2.6 micrometers. For each inhalation session, transfer the contents of two 1 ml vials of Iloprost Zentiva 10 mcg/ml solution for nebulizer into the nebulizer chamber immediately before use. Two programs can be used:
• PI Program 1: 5 micrograms of active substance over 25 inhalation cycles via mouthpiece.
• P2 Program 2: 2.5 micrograms of active substance over 10 inhalation cycles via mouthpiece.

The preset program is selected by the physician.
Venta-Neb alerts the patient to inhale with an optical and an acoustic signal. It stops automatically at the end of the administration of the preset dose. To obtain droplets of optimal size for the administration of Iloprost Zentiva, the use of the green deflector is recommended. For further details, please refer to the instruction manual of the Venta-Neb nebulizer.

The efficacy and tolerability of inhaled iloprost administered via other nebulization systems, which provide different nebulization characteristics to the iloprost solution, have not been established.