Iloprost zentiva

Package leaflet: Information for the user

Iloprost Zentiva, 20 micrograms/ml, solution for nebulisation
Iloprostum
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 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 other people, even if their symptoms are the same as yours.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

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

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

What Iloprost Zentiva is used for
Iloprost Zentiva is used to treat moderate idiopathic pulmonary arterial hypertension in adult patients. Idiopathic pulmonary arterial hypertension is a type of pulmonary hypertension where the cause of high blood pressure is unknown.
In this disease, blood pressure in the blood vessels between the heart and lungs is too high.
Iloprost Zentiva is used to improve exercise capacity (ability to perform physical activity) and reduce disease symptoms.

How Iloprost Zentiva works
Inhaling the generated aerosol allows Iloprost Zentiva to reach the lungs, where it can act most effectively on the artery between the heart and the lungs. Improved blood flow leads to better oxygen supply to the body and reduces strain 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, 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:
  • reduced 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 function (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 ischaemic 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 this 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). The doctor will closely monitor the patient.
• Blood pressure will be checked before treatment; if it is too low (below 85 mmHg for the higher 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 the patient is taking, 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 exertion. Fainting may be due to the underlying disease. If fainting worsens, inform the doctor. The doctor may consider adjusting the dose or changing the treatment.
• If the patient has heart disease, e.g. right ventricular failure, and feels 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 oedema. The doctor may consider changing the treatment.
• If the patient experiences difficulty breathing, coughing up blood, and/or excessive sweating, these may be symptoms of fluid in the lungs (pulmonary oedema). Stop using Iloprost Zentiva immediately and contact the doctor without delay. The doctor will investigate the cause and take appropriate action.
• If the patient has liver function disorders or very severe kidney disease requiring dialysis, inform the doctor. The patient may be gradually introduced to the target dose, or may be prescribed a lower dose of Iloprost Zentiva than usually given to other patients (see section 3 “How to use Iloprost Zentiva”).

Contact of Iloprost Zentiva with skin or accidental ingestion

• DO NOT allow the Iloprost Zentiva solution to come into contact with skin or eyes. If this occurs, immediately rinse the skin or eyes thoroughly 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 a doctor immediately.

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, has recently taken, or plans to take. The interaction between Iloprost Zentiva and certain medicines may affect the patient’s condition. 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,
  • 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 interaction between food and drink and the effect 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 may 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 is planning 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 is not recommended 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 may lower 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 such symptoms occur.

Iloprost Zentiva contains ethanol
This medicine contains 1.5 mg of alcohol (ethanol) per ampoule, equivalent to 1.62 mg/ml (96% v/v ethanol). The amount 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 prescribed by the doctor. In case of doubt, consult the doctor.
The appropriate dose of Iloprost Zentiva and duration of treatment depend on the individual patient's condition. The doctor will advise the patient accordingly. The patient must not change the prescribed dose without consulting the doctor.
Various nebulizers can be used to administer Iloprost Zentiva 20 micrograms/ml.

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

If tolerance to Iloprost Zentiva 20 micrograms/ml is low, the patient should consult the doctor, 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 doctor will monitor the treatment after initiation of the Breelib nebulizer to assess whether the patient tolerates the dose and inhalation rate adequately.

• I-Neb AAD nebulizer The duration of inhaled treatment with Iloprost Zentiva 10 micrograms/ml had been frequently extended in the patient, therefore the doctor decided to switch to Iloprost Zentiva 20 micrograms/ml. Iloprost Zentiva 20 micrograms/ml is twice as concentrated as Iloprost Zentiva 10 micrograms/ml. The active substance may thus be delivered to the lungs more rapidly. The doctor will supervise the patient’s treatment during the transition from Iloprost Zentiva 10 micrograms/ml to Iloprost Zentiva 20 micrograms/ml to ensure the patient tolerates the higher concentration. The dose intended for one inhalation should be administered 6 to 9 times daily, according to the patient's individual needs and tolerance. Depending on individual requirements, Iloprost Zentiva may be used for long-term treatment.

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 doctor will initiate Iloprost Zentiva gradually and may prescribe a lower number of daily inhalations. Treatment should be started at a dose of 2.5 micrograms of iloprost using one ampoule of Iloprost Zentiva. Doses should be separated by 3–4 hour intervals (corresponding to a maximum of 6 doses per day). The doctor may then cautiously reduce the interval between doses based on the patient's tolerance to treatment. If the doctor decides to further increase the dose to 5 micrograms, 3–4 hour intervals between doses should initially be maintained again, and subsequently shortened 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 doctor or pharmacist.
The patient should ask the doctor for assistance in thoroughly familiarizing themselves with the correct use of the nebulizer. The nebulizer must not be changed without consulting the treating physician.
Method of inhalation
A new ampoule of Iloprost Zentiva should be used for each inhalation. Just before starting inhalation, break the glass ampoule and transfer the solution to the medication chamber, following the nebulizer's instructions for use.
Strictly follow the instructions provided with the nebulizer, especially those concerning hygiene and cleaning of the nebulizer.
Iloprost Zentiva must always be used exactly as prescribed by the doctor.

• Iloprost Zentiva solution for nebulization is administered using nebulizers prescribed by the doctor (Breelib system, I-Neb AAD).
• The nebulizer converts the Iloprost Zentiva solution into an aerosol, which should be inhaled through the mouth.
• For inhalation, a mouthpiece should be used to prevent contact of Iloprost Zentiva with the skin. A face mask must not be used.
• Follow the instructions provided with the nebulizer. In case of doubt, contact the doctor 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 administered should be ventilated or equipped with an exhaust system. Other individuals could be inadvertently exposed to Iloprost Zentiva present in the air. In particular, newborns, infants, and pregnant women must not be exposed to Iloprost Zentiva. They should not be present in the same room during Iloprost Zentiva inhalation.

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

• I-Neb AAD
  1. Immediately before starting inhalation, break and open the glass ampoule of Iloprost Zentiva, 20 micrograms/ml containing 1 ml of solution, and transfer the entire content into the medication chamber of the nebulizer.
  2. The predetermined 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 distinct color. Each medication chamber is assigned a control disc of matching color:
     • For Iloprost Zentiva, 20 micrograms/ml (5 microgram dose), the medication chamber with a gold clip and gold control disc must be used.
     • To ensure that the patient receives the recommended dose, verify that the color of the medication chamber matches the color of the control disc. Both must be of the same color.

Since the I-Neb AAD device can be used for both Iloprost Zentiva 10 micrograms/ml and Iloprost Zentiva 20 micrograms/ml, the table below summarizes the instructions for using the device with the two different concentrations of Iloprost Zentiva.

Detailed information is provided in the nebulizer user manual; you may 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 immediately,
• contact your physician. The physician will monitor the patient's condition and treat the symptoms accordingly. There is no known specific antidote.

Missed dose of Iloprost Zentiva
Do not take a double dose to make up for a missed dose. Consult your physician for further advice.
Discontinuation of Iloprost Zentiva treatment
If you discontinue or wish to discontinue treatment, discuss this first with your physician.
If you have any further doubts regarding the use of this medicine, please consult your physician, 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. 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)), especially when used concomitantly with anticoagulant medicines. 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 bleeding) have been reported very rarely.

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

• fainting (syncope) – this 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 unknown (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, grouped by 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)
• limb swelling (peripheral oedema)

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

• breathing difficulties (dyspnoea)
• dizziness
• vomiting
• diarrhoea
• pain during 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 strong heartbeat (palpitations)

Frequency unknown (cannot be estimated from the available data):

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

Other possible symptoms

• Oedema, mainly in the ankle and leg area due to fluid retention (peripheral oedema), is a very common symptom of the disease itself, but may also occur during treatment with iloprost.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 the representative of the marketing authorisation holder in Poland.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Iloprost Zentiva

Keep this medicine out of 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 conditions are required. Do not freeze.
Any remaining Iloprost Zentiva solution left 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 in use. This will help protect the environment.

6. Contents of the pack and other information

What Iloprost Zentiva contains

• The active substance is iloprost. Each 1 ml ampoule contains 20 micrograms of iloprost (as iloprost trometamol).
• The other components 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 free from particles, intended for inhalation using Breelib or I-Neb nebulisers.
Iloprost Zentiva is supplied in a 1 ml clear glass type I ampoule coded with coloured rings (yellow, red), contained in a PVC foil blister pack within a cardboard box.
Iloprost Zentiva is available in pack sizes containing:
30 x 1 ml (6 blisters of 5 ampoules or 5 blisters of 6 ampoules) in a cardboard box
42 x 1 ml (8 blisters of 5 ampoules and 1 blister with 2 ampoules, or 7 blisters of 6 ampoules) in a cardboard box
168 x 1 ml (33 blisters of 5 ampoules and 1 blister with 3 ampoules, or 28 blisters of 6 ampoules) in a cardboard box
A multipack containing 160 ampoules (comprising 4 cardboard boxes, each containing 8 blisters of 5 ampoules).
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:
Poland, Czech Republic: Iloprost Zentiva
Italy:
Germany: Iloprost Zentiva 20 Mikrogramm/ml Lösung für einen Vernebler
United Kingdom: Iloprost 20 microgram/ml nebuliser solution

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw, Poland
tel.: +48 22 375 92 00

Information intended exclusively for healthcare professionals:

Instructions for use and handling of the medicinal product
Patients treated with one type of nebulizer should not switch to a different type without close supervision by their physician, as different nebulizers have been shown to produce aerosols with slightly different physical characteristics and differ in the rate at which the solution is delivered (see section 5.2 Pharmaceutical characteristics).

To minimize unintended exposure, adequate room ventilation is recommended.

• Breelib: When using the Breelib nebulizer, follow the instructions provided with the device. The medication chamber should be filled with Iloprost Zentiva immediately before use.

• I-Neb AAD The I-Neb AAD device is a portable, handheld nebulization system utilizing vibrating mesh technology. This system generates droplets using ultrasound, forcing the solution through a mesh. The nebulizer monitors the patient's breathing pattern to determine the necessary nebulization time required to deliver a pre-set dose of 5 micrograms of iloprost from the product Iloprost Zentiva 20 micrograms/ml solution for nebulization. The nebulizer delivers 5 micrograms of iloprost at the mouthpiece. The Mass Median Aerodynamic Diameter (MMAD) of the aerosol ranges between 1–5 micrometers. When using the I-Neb AAD device, the following instructions for use must be followed. The pre-set dose in the I-Neb AAD device is controlled by the medication chamber together with a control disc. Each medication chamber is assigned a color-coded control disc. For each inhalation using the I-Neb AAD nebulization device, the contents of one ampoule containing 1 ml of Iloprost Zentiva 20 micrograms/ml solution for nebulization shall be transferred directly before use into the appropriate medication chamber of the nebulizer with a gold slider and a gold disc. Since the I-Neb AAD device can be used to administer both Iloprost Zentiva 10 micrograms/ml and Iloprost Zentiva 20 micrograms/ml products, the table below summarizes the instructions for use of I-Neb for the two concentrations of Iloprost Zentiva:

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