Iloprost zentiva

Package leaflet: Information for the user

Iloprost Zentiva, 10 micrograms/ml, solution for nebulization
Iloprostum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

What Iloprost Zentiva is
The active substance in Iloprost Zentiva is iloprost. It mimics the action of a naturally occurring substance in the body called prostacyclin. Iloprost Zentiva reduces unwanted obstruction or narrowing of blood vessels, allowing increased blood flow through the vessels.

What Iloprost Zentiva is used for
Iloprost Zentiva is used in the treatment of moderate pulmonary arterial hypertension in adult patients. Pulmonary arterial hypertension is a type of high blood pressure in the lungs for which the cause is unknown.

In this disease, blood pressure in the blood vessels between the heart and the lungs is too high.

Iloprost Zentiva is used to improve exercise capacity (the ability to perform physical activity) and to reduce disease symptoms.

How Iloprost Zentiva works
Inhaling the generated aerosol delivers Iloprost Zentiva to the lungs, where it can act most effectively on the pulmonary artery (the blood vessel between the heart and the lungs). Improved blood flow leads to better oxygen supply to the body and reduces the workload on the heart.

1. Important Information Before Using Iloprost Zentiva

When not to use Iloprost Zentiva

• if the patient is allergic to iloprost or any of the other ingredients of this medicine (listed in section 6).
• if the patient is at risk of bleeding – for example, if the patient has an active gastric or duodenal ulcer (peptic ulcer), if the patient has sustained physical injury (trauma), or if the patient is at risk of intracranial bleeding.
• if the patient has heart diseases, such as:
  • poor blood flow to the heart muscle (severe coronary artery disease or unstable angina pectoris). Symptoms may include chest pain.
  • myocardial infarction (heart attack) within the last 6 months.
  • weakened heart (uncompensated heart failure), if this condition is not controlled by a physician.
  • severe, unstable heart rhythm.
  • defective heart valve (congenital or acquired), causing poor heart function (not related to pulmonary hypertension).
• if the patient has had a stroke or any other event reducing blood flow to the brain (e.g., transient ischemic attack) within the last 3 months.
• if pulmonary hypertension is caused by obstruction or narrowing of the pulmonary vein (pulmonary veno-occlusive disease).

Warnings and precautions
Before starting treatment with Iloprost Zentiva, discuss 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 muscles in the walls of small airways) and wheezing. Inform your doctor if the patient has a lung infection, severe asthma, or chronic lung disease (chronic obstructive pulmonary disease). Your doctor will closely monitor the patient.
• Blood pressure will be checked before treatment; if it is too low (below 85 mmHg for the systolic value), treatment with Iloprost Zentiva should not be initiated.
• Take special care to avoid symptoms of low blood pressure, such as fainting and dizziness:
• Inform your doctor about all medications being taken, as their combined effect with Iloprost Zentiva may further lower blood pressure (see below “Other medicines and Iloprost Zentiva”).
• Rise slowly when getting up from a chair or bed.
• If fainting occurs immediately upon rising from bed, it may be beneficial for the patient to take the first daily dose while still in bed.
• If the patient is prone to fainting, avoid excessive exertion, such as physical exercise. It may be beneficial to use Iloprost Zentiva before physical activity. Fainting may be due to the underlying disease. If fainting worsens, inform the doctor. The doctor may consider adjusting the dose or changing treatment.
• If the patient has heart disease, e.g., right ventricular failure, and feels that their condition is worsening, they should inform the doctor. Symptoms may include swollen feet and ankles, shortness of breath, palpitations, increased urination at night, or edema. The doctor may consider changing treatment.
• If the patient experiences difficulty breathing, coughing up blood, and/or excessive sweating, these may be signs of fluid in the lungs (pulmonary edema). Stop using Iloprost Zentiva and contact the doctor immediately. The doctor will investigate the cause and take appropriate action.
• If the patient has impaired liver function or very severe kidney disease requiring dialysis, inform the doctor. The patient may require gradual introduction of the target dose or a lower dose of Iloprost Zentiva than usually prescribed to other patients (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 skin or eyes. If this occurs, immediately rinse the skin or eyes with large amounts of water.
• DO NOT drink or swallow the Iloprost Zentiva solution. In case of accidental ingestion, 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 pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. The interaction between Iloprost Zentiva and certain medicines may affect the patient’s body. Inform the doctor if the patient is taking any of the following medicines:

• Medicines used to treat high blood pressure or heart disease, such as:
• beta-blockers,
• vasodilating nitrates,
• angiotensin-converting enzyme (ACE) inhibitors. Blood pressure may decrease further. The doctor may adjust the dosage.
• Medicines that thin the blood or inhibit blood clotting, including:
  • acetylsalicylic acid (ASA – an ingredient in many fever-reducing and pain-relieving medicines),
  • heparin,
  • coumarin-derived anticoagulants such as warfarin or phenprocoumon,
  • non-steroidal anti-inflammatory drugs (NSAIDs),
  • 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. The doctor will closely monitor the patient.

Before taking any medicine, consult your doctor or pharmacist, who can provide more information about medicines that should be used cautiously or avoided during treatment with Iloprost Zentiva.
Taking Iloprost Zentiva with food and drink
No effect of food or drink on the action of Iloprost Zentiva is expected. However, eating or drinking should be avoided during inhalation.
Pregnancy

• If the patient has pulmonary hypertension, she should avoid becoming pregnant, as pregnancy may worsen her condition and could even be life-threatening.
• If the patient is of childbearing age, she should use an effective method of contraception from the start of treatment and during treatment.
• If the patient is pregnant, suspects she may be pregnant, or plans to become pregnant, she should inform the doctor immediately. Iloprost Zentiva may be used during pregnancy only if the doctor decides that the potential benefits outweigh the potential risks to the fetus.

Breast-feeding
It is not known whether Iloprost Zentiva passes into human milk. Potential risk to the breastfed infant cannot be excluded, and breast-feeding should be avoided during treatment with Iloprost Zentiva.
Before taking any medicine, consult your doctor or pharmacist.
Newborns, infants, and pregnant women should not be present in the same room
where the patient is inhaling Iloprost Zentiva.
Driving and operating machinery
Iloprost Zentiva lowers blood pressure in some patients and may cause dizziness or a feeling of emptiness in the head. Do not drive or operate any machinery or tools if these symptoms occur.
Iloprost Zentiva contains ethanol
This medicine contains 0.78 mg of alcohol (ethanol) per ampoule, equivalent to 0.81 mg/ml (96% v/v ethanol). The content in 1 ml of 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 cause any noticeable effects.

3. How to use Iloprost Zentiva

Treatment with Iloprost Zentiva must be initiated and monitored only by a physician experienced in the management of pulmonary hypertension.
Dosage and duration of treatment
This medicine should always be used exactly as directed by the physician. If in doubt, consult your doctor.
The appropriate dose of Iloprost Zentiva and the duration of treatment depend on the individual patient's condition. The physician will provide advice. The patient must not change the prescribed dose without consulting the physician.
Different nebulizers may be used to administer Iloprost Zentiva. Depending on the type of device used and the prescribed dose, either 1 ml or 2 ml of Iloprost Zentiva should be applied.

• Breelib nebulizer
  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 this dose well, the next dose should be increased by using another available product containing 20 micrograms/ml of iloprost. The patient should then continue with this dosing regimen.
  If the higher dose is poorly tolerated, consult the physician, who may decide to reduce the dose and switch to Iloprost Zentiva 10 micrograms/ml.
  Most patients perform 6 to 9 inhalations per day. One inhalation using the Breelib nebulizer usually takes about 3 minutes.
  The physician will monitor the treatment after starting use of the Breelib nebulizer to ensure the patient tolerates the dose and inhalation rate well.

• I-Neb AAD nebulizer
  When starting treatment with Iloprost Zentiva, the initial inhaled dose should usually be 2.5 micrograms of iloprost delivered via mouthpiece. If the patient tolerates this dose well, the dose should be increased to 5 micrograms of iloprost. The patient should continue with this dosing regimen. If the patient does not tolerate the 5 microgram dose, reduce the dose to 2.5 micrograms.
  Most patients perform 6 to 9 inhalations per day. One inhalation using the I-Neb AAD nebulizer usually takes about 4 to 10 minutes, depending on the prescribed dose.

• Venta-Neb nebulizer (2 vials of Iloprost Zentiva)
  When starting treatment with Iloprost Zentiva, the initial inhaled dose should usually be 2.5 micrograms of iloprost delivered via mouthpiece. If the patient tolerates this dose well, the dose should be increased to 5 micrograms. The patient should continue with this dosing regimen. If the patient does not tolerate the 5 microgram dose, it should be reduced to 2.5 micrograms.
  Most patients perform 6 to 9 inhalations per day. One inhalation using the Venta-Neb nebulizer usually takes about 4 to 10 minutes, depending on the prescribed dose.
  Depending on individual needs, Iloprost Zentiva may be used long-term.

Patients with kidney or liver disease
There is no need to adjust the dose in patients with mild or moderate renal impairment (patients with creatinine clearance >30 ml/min).
If the patient has severe renal impairment requiring dialysis, or if the patient has liver problems, the physician should initiate treatment with Iloprost Zentiva gradually and may prescribe a lower number of inhalations per day. Treatment should start with a dose of 2.5 micrograms of iloprost using 1 vial of Iloprost Zentiva. Doses should be separated by 3–4 hour intervals (corresponding to a maximum of 6 doses per day). The physician may then cautiously reduce the interval between doses based on the patient's tolerance to treatment. If the physician decides to further increase the dose to 5 micrograms, initially reintroduce 3–4 hour intervals between doses and gradually shorten them according to the patient's tolerance.

If the patient feels that the effect of Iloprost Zentiva is too strong or too weak, this should be discussed with the physician or pharmacist.
Ask the physician to help the patient become fully familiar with the correct use of the nebulizer. Do not change the nebulizer without consulting the treating physician.

Method of inhalation
A new vial of Iloprost Zentiva should be used for each inhalation. Just before starting inhalation, break the glass vial and transfer the solution into the medication chamber, following the nebulizer's user instructions.
Strictly follow the instructions provided with the nebulizer, especially those concerning hygiene and cleaning of the device.
Iloprost Zentiva must always be used exactly as prescribed by the physician.

• Iloprost Zentiva nebulizing solution is administered using nebulizers prescribed by the physician (Breelib, Venta-Neb or I-Neb AAD systems).
• The nebulizer converts the Iloprost Zentiva solution into an aerosol, which should be inhaled through the mouth.
• A mouthpiece must be used for inhalation to prevent contact of Iloprost Zentiva with the skin. Do not use a face mask.
• Follow the instructions supplied with the nebulizer. In case of doubt, contact the physician or pharmacist again.
• Any Iloprost Zentiva solution remaining in the nebulizer after inhalation must be discarded (see section 5).

Room ventilation
The room where Iloprost Zentiva has been used should be ventilated or equipped with an active ventilation system. Other individuals could be accidentally exposed to Iloprost Zentiva present in the air of the room. In particular, newborns, infants, and pregnant women must not be exposed to Iloprost Zentiva. They should not be present in the same room during inhalation of Iloprost Zentiva.

• Breelib: The medication chamber must be filled with Iloprost Zentiva immediately before use. Follow the nebulizer's user instructions when filling the chamber.

• I-Neb AAD
  1. Immediately before starting inhalation, break and open the glass ampoule containing 1 ml of solution and transfer the entire contents into the medication chamber of the nebulizer.
  2. The preset dose in the I-Neb AAD device is controlled by the medication chamber together with the control disc. There are two different medication chambers, each marked with a different colour. Each medication chamber is assigned control discs of matching colours:
     • For the 2.5 microgram dose, use the medication chamber with a red slide and red control disc.
     • For the 5 microgram dose, use the medication chamber with a purple slide and purple control disc.
  3. To ensure the patient receives the prescribed dose, verify that the medication chamber colour matches the control disc colour. They must be the same colour—red for the 2.5 microgram dose or purple for the 5 microgram dose.

The table below provides a summary of the instructions for use of Iloprost Zentiva:

• Venta-Neb
  1. Immediately before starting inhalation, break open and open 2 glass ampoules containing 1 ml of solution each, and transfer their entire contents into the chamber of the nebulizer intended for the medicinal product.
  2. Two types of programs can be used:
  3. The physician will adjust Venta-Neb according to the program corresponding to the recommended dose to be administered to the patient.
• P1 Program 1: 5 micrograms of active substance at the mouthpiece; 25 inhalations.
• P2 Program 2: 2.5 micrograms of active substance at the mouthpiece; 10 inhalations. 4. To achieve the optimal particle size of Iloprost Zentiva medicinal product, use the green deflector.

Detailed information is provided in the nebulizer user manual; you can also consult your physician.
Use of a higher than recommended dose of Iloprost Zentiva
Using a higher than recommended dose of Iloprost Zentiva may lead to dizziness, headache, sudden facial flushing, nausea, jaw pain or back pain. The patient may also experience decreased or increased blood pressure, bradycardia (slowed heart rate), tachycardia (increased heart rate), vomiting, diarrhea or limb pain. If any of these symptoms occur after using a higher than recommended dose of Iloprost Zentiva, you should:

• stop inhalation,
• contact your doctor.

The doctor will monitor the patient's condition and treat the symptoms accordingly. There is no known specific antidote.
Missed dose of Iloprost Zentiva
Do not use a double dose to make up for a missed dose. Consult your doctor on how to proceed.
Discontinuation of Iloprost Zentiva treatment
If you are considering interrupting or stopping treatment, discuss this first with your doctor.
If you have any further doubts regarding the use of this medicine, please consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following serious adverse reactions may occur. If any of these occur, you should
inform your doctor immediately.
Very common (may affect more than 1 in 10 people):

• Bleeding events (mostly nosebleeds and coughing up blood from the respiratory tract (haemoptysis)) may very commonly occur, especially when the medicine is used concomitantly with anticoagulants. The risk of bleeding may increase in patients who are also receiving antiplatelet agents or
  anticoagulant medicines (see also section 2). Fatal cases of intracranial haemorrhage (cerebral and intracranial haemorrhage) have been reported very rarely.
  Common (may affect less than 1 in 10 people):

• Fainting (syncope) is a symptom of the disease itself, but may also occur during treatment with Iloprost Zentiva (advice on how to prevent fainting can be found in 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 list below presents possible adverse reactions according to their likelihood of occurrence:
Very common (may affect more than 1 in 10 people):

• Vasodilation. Symptoms may include hot flushes or facial flushing
• Chest discomfort and/or chest pain
• Cough
• Headache
• Nausea
• Jaw pain, jaw muscle spasm (trismus)
• Swelling of the limbs (peripheral oedema)

Common (may affect less than 1 in 10 people):

• Breathing difficulties (dyspnoea)
• Dizziness
• Vomiting
• Diarrhoea
• Pain on swallowing (irritation of the throat and larynx)
• Throat irritation
• Irritation of the mouth and tongue, including pain
• Rash
• Rapid heartbeat (tachycardia)
• Awareness of rapid or forceful heartbeat (palpitations)

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

• Decrease in platelet count (thrombocytopenia)
• Hypersensitivity (e.g. allergy)
• Taste disturbances

Other possible symptoms

• Swelling, mainly around 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 adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse reactions helps 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 stated on the label and on the
packaging after "EXP". The expiry date refers to the last day of the stated month.
No special storage precautions are required. Do not freeze.
Any residual solution of Iloprost Zentiva remaining in the nebulizer after inhalation must be
discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer used. Such measures will help
protect the environment.

6. Contents of the package and other information

What Iloprost Zentiva contains

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

What Iloprost Zentiva looks like and contents of the pack
Iloprost Zentiva is a clear, colourless solution free from solid particles, intended for inhalation using Breelib, I-Neb or Venta-Neb nebulizers.
Iloprost Zentiva is supplied in a 1 ml clear glass type I ampoule with a blue ring, containing 1 ml of solution, placed in a blister and cardboard carton.
Iloprost Zentiva is available in pack sizes 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 Měcholupy, 102 37 Prague 10, Czech Republic
Manufacturer
Zentiva k.s., U Kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic
This medicinal product is authorised in the European Economic Area countries under the following names:
Germany, Poland, Czech Republic, Italy Iloprost Zentiva
United Kingdom Iloprost 10 microgram/ml
(Northern Ireland)
For further information about this medicinal product, please contact the local 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

Information intended exclusively for medical professionals:

Instructions for use and handling of the medicinal product
Patients treated with one type of nebulizer should not switch to another type without strict
supervision by the attending physician, as different nebulizers have been shown to produce aerosols
with slightly different physical characteristics and vary in the rate of solution delivery (see section 5.2
Pharmaceutical characteristics).
To minimize unintended exposure, adequate room ventilation is recommended.
When using the Breelib nebulizer, follow the instructions provided with the device.
The medication chamber should be filled with Iloprost Zentiva immediately before use.

| Device | Medication | Iloprost dose per mouthpiece | Estimated inhalation time |
|------------|----------------|-------------------------------|-------------------------------|
| Breelib | Iloprost Zentiva | 2.5 micrograms | 3 min |
| | 10 micrograms/ml | | |

• I-Neb AAD – The I-Neb AAD device is a portable, hand-held nebulization system with vibrating mesh technology. This system generates droplets using ultrasound, forcing the solution through a mesh. The I-Neb AAD nebulizer has been shown to be suitable for administering the medicinal product Iloprost Zentiva, 10 micrograms/ml. The measured MMAD (Mass Median Aerodynamic Diameter) of the aerosol droplets was 2.1 micrometers. The nebulizer monitors the patient's breathing pattern to determine the nebulization time required to deliver a pre-set dose of either 2.5 or 5 micrograms of iloprost.

The dose delivered by the I-Neb AAD device is controlled by the medication chamber together with a control disc. Each medication chamber is matched with a color-coded control disc.
For the 2.5 microgram dose, use the medication chamber with a red slider together with the red control disc.
For the 5 microgram dose, use the medication chamber with a purple slider together with the purple control disc.
For each inhalation using the I-Neb AAD device, the contents of one 1 ml vial of Iloprost Zentiva medicinal product should be transferred directly into the medication chamber immediately before use.

The table below provides a summary of the I-Neb instructions for the medicinal product
Iloprost Zentiva:

• Venta-Neb It has been demonstrated that the medicinal product Iloprost Zentiva, 10 micrograms/ml, can be administered using the Venta-Neb - a portable, battery-operated ultrasonic nebulizer. The measured MMAD value of aerosol droplets was 2.6 micrometers. Immediately before each inhalation session using the Venta-Neb device, the contents of two 1 ml ampoules of the medicinal product Iloprost Zentiva, 10 micrograms/ml, should be introduced into the medication chamber of the nebulizer. Two types of programs can be used:
• P1 Program 1: 5 micrograms of active substance at the mouthpiece; 25 inhalations.
• P2 Program 2: 2.5 micrograms of active substance at the mouthpiece; 10 inhalations.

The physician selects the appropriate program.
The Venta-Neb device provides visual and acoustic signals indicating the inhalation moment. Nebulization is automatically stopped after the predetermined dose has been delivered. To achieve the optimal particle size of the medicinal product Iloprost Zentiva, the green deflector must be used. Detailed information is provided in the Venta-Neb nebulizer user manual.

The efficacy and safety of iloprost inhalations administered using other nebulization systems with different characteristics of iloprost solution nebulization have not been established.