ILOPROST 100 MICROGRAMS/ML Concentrate for infusion solution

Зміст інструкції

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

Iloprost Zentiva Italia 100 micrograms/ml concentrate for solution for infusion
Generic medicine

Read this leaflet carefully before using this medicine as 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.
• If you experience any side effects, including those not listed in this leaflet, ask your doctor, pharmacist or nurse. See section 4. Contents of this leaflet
• 1. What Iloprost Zentiva Italia is and what it is used for
• 2. What you need to know before you are given Iloprost Zentiva Italia
• 3. How to use Iloprost Zentiva Italia
• 4. Possible side effects
• 5. How to store Iloprost Zentiva Italia
• 6. Contents of the pack and other information

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

Iloprost Zentiva Italia contains the active ingredient iloprost, a substance that mimics a natural substance
called prostacyclin. Iloprost and prostacyclin exert numerous actions including the inhibition of
blood coagulation when there is a risk of thrombosis and embolisms in veins or arteries, a
dilation of small blood vessels and a stimulation of the physiological mechanisms that dissolve blood clots (thrombi).
Iloprost Zentiva Italia is used to treat:

• Obliterating thromboangiitis in advanced stage (Bürger's disease - an inflammatory disease of the veins that causes obstruction of blood vessels and damage to the veins of the extremities such as hands and feet), in cases where revascularization surgery cannot be performed;
• Raynaud's phenomenon (extreme contraction of the blood vessels in the fingers of the hands and feet) in patients who do not respond to other therapeutic measures.
• Severe occlusive peripheral arteriopathy (severe reduction of blood flow to the lower limbs), particularly in patients at risk of amputation in whom surgery or angioplasty cannot be performed.

2. What you need to know before you take Iloprost Zentiva Italia

Do not take Iloprost Zentiva Italia:

• if you are allergic to iloprost or any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or breastfeeding (see “Pregnancy, breastfeeding and fertility”);
• if you have a condition with an increased risk of bleeding - for example, in case of gastric (stomach) or duodenal ulcer, trauma or bleeding inside the skull;
• if you suffer from poor blood flow to the heart muscle (severe coronary heart disease or unstable angina), causing chest tightness due to lack of oxygen in the heart muscle;
• if you have had a heart attack in the last 6 months;
• if you suffer from a weak heart (heart failure) in NYHA classes II - IV;
• if you suffer from irregular heartbeats (arrhythmias);
• if you suspect fluid overload in the lungs (pulmonary congestion) accompanied by difficulty breathing. Talk to your doctor if you think any of the above situations apply to you.

Warnings and precautions
Talk to your doctor before taking Iloprost Zentiva Italia.

• If you need an urgent amputation (e.g. in case of infected gangrene), surgery should not be postponed.
• If you smoke, it is strongly recommended that you quit smoking.
• If you have liver or kidney problems, the dose of Iloprost Zentiva Italia may need to be reduced.
• If you suffer from low blood pressure, in this case you must pay particular attention to avoid a further drop in blood pressure (hypotension).
• Pay attention to the possibility of hypotension when getting up from a lying position to an upright position after the infusion has been completed. You should get up slowly in order to help your body adjust to its new position and blood pressure.
• If you suffer from heart disease, you will be carefully monitored.
• If you have had a stroke or an interruption of blood flow to the brain (a transient ischemic attack) in the last 3 months.
• If undiluted Iloprost Zentiva Italia is injected near a vein, this may cause local changes at the injection site.

If Iloprost Zentiva Italia comes into contact with the skin and eyes.
Avoid contact of this medicine with the skin and eyes. If it comes into contact with the skin, Iloprost can
cause a persistent redness of the skin (erythema). If contact occurs, immediately rinse
skin and eyes with plenty of water or saline solution.
Iloprost Zentiva Italia should not be swallowed.

Children and adolescents
No data are available on the use of iloprost in children.

Other medicines and Iloprost Zentiva Italia
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines.
Iloprost Zentiva Italia can affect how other medicines work and vice versa.
Tell your doctor if you are taking:

• Medicines used to treat high blood pressure or heart disease (such as beta-blockers, calcium channel blockers, vasodilators, ACE inhibitors). Your blood pressure may drop further. Your doctor may adjust the dose of Iloprost Zentiva Italia.
• Medicines that thin the blood or prevent blood clotting. This may increase the risk of bleeding. These include: acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs), heparin, or coumarin-like anticoagulants, phosphodiesterase inhibitors and nitro-vasodilators. If bleeding occurs, treatment with Iloprost Zentiva Italia should be stopped.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
This medicine should not be given during pregnancy or while breastfeeding.
If you are of childbearing potential, use adequate contraception during treatment.

Iloprost Zentiva Italia contains ethanol and sodium
This medicine contains 7.66 mg of alcohol (ethanol) in each ml of concentrate which is equivalent to 8.1 mg
of ethanol 96%. The amount of ethanol in this medicine is equivalent to less than 0.2 ml of beer or 0.08
ml of wine. The small amount of alcohol in this medicine will not produce significant effects.
This medicine contains 3.54 mg of sodium in 1 ml of the concentrate, i.e. essentially “sodium-free”.

3. How to use Iloprost Zentiva Italia

Iloprost Zentiva Italia must be administered only in hospital settings or in adequately equipped outpatient clinics
under strict supervision.
The infusion solution must be prepared immediately before daily infusion to ensure
sterility.
Iloprost Zentiva Italia must be administered only after dilution.
Iloprost Zentiva Italia after dilution will be administered to you through a vein by infusion,
for approximately 6 hours a day through a central venous catheter or peripheral vein.
The dose will be adjusted based on individual tolerability within a range of 0.5 to 0.2 ng iloprost/kg/min.
The exact infusion rate will be calculated based on body weight.
For further information for the doctor or healthcare professional regarding the preparation of the
dilution, see section 6 “The following information is intended exclusively for healthcare professionals”.
During the first 2-3 days of treatment, the individually tolerated dose will be determined. For this
purpose, your doctor will start treatment with a low dose. If you experience adverse
effects such as headache, nausea and low blood pressure, inform your doctor immediately.
The infusion rate must be reduced until a tolerated dose is found. If the adverse effects are
severe, the infusion will be stopped. Treatment should then continue (usually up to 4 weeks) with the
dose identified as tolerable in the first 2-3 days.
Blood pressure and
heart rate will be measured at the beginning of the infusion and after each dose increase.
The duration of treatment is 4 weeks. In the case of treatment for Raynaud's phenomenon, shorter treatment periods (3-5 days) are often
sufficient to achieve improvement for several weeks.

Patients with kidney or liver problems
If you have kidney problems requiring dialysis or liver cirrhosis, the elimination of iloprost is reduced and a
dose reduction will be necessary (e.g. half the recommended dose). Tell your doctor if you have liver or kidney problems.

If you are given more Iloprost Zentiva Italia than you should
The symptoms of overdose may include: low blood pressure
(hypotension), headache, flushing (sudden redness of the face), nausea, vomiting and diarrhea.
Other possible symptoms are increased blood pressure, slowed or accelerated heartbeat,
pain in the limbs or back.
If you experience symptoms that may indicate that you have been given too much Iloprost Zentiva Italia,
the infusion of Iloprost Zentiva Italia must be stopped, and the symptoms must be treated. A specific antidote is not known.
In case of accidental ingestion, contact your doctor immediately.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
In patients treated with iloprost, the most serious side effects that have been reported as fatal
or life-threatening are:

• Common(may affect up to 1 in 10 people): particularly low blood pressure (hypotension), fast heartbeat (tachycardia), chest pain/discomfort caused by insufficient blood flow to the heart (angina pectoris) - especially in patients with heart failure,

difficulty breathing (dyspnea).

• Uncommon(may affect up to 1 in 100): Stroke (cerebrovascular accident), heart attack, breathing problems or chest pain caused by the presence of blood clots in the lungs (pulmonary embolism), heart failure, convulsions (seizures), asthma, difficulty breathing or coughing up blood due to fluid accumulation in the lungs (pulmonary edema). Another group of side effects relates to local reactions at the infusion site. For example, redness and pain may appear at the infusion site or cutaneous vasodilation which can lead to the appearance of superficial streaked redness along the course of the vein.

Other possible side effects are listed below according to their frequency:

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

• headache
• facial flushing (redness)
• nausea, vomiting
• excessive sweating (hyperhidrosis).

These side effects are likely to occur at the beginning of treatment, during dose adjustment,
to identify the best tolerable dose for the individual patient. However, they generally disappear
quickly by reducing the dose.

Common(may affect up to 1 in 10 people)

• Loss of appetite.
• Apathy, confusion.
• Dizziness/vertigo, numbness or tingling (paresthesia), palpitations, increased sensitivity to pain or touch (hyperesthesia), burning sensation, restlessness/agitation, sedation, drowsiness.
• Slowed heartbeat.
• High blood pressure.
• Diarrhea, abdominal discomfort, stomach pain.
• Jaw pain, jaw spasm, locked jaw (trismus), muscle pain, joint pain.
• Pain, fever, increased body temperature, feeling of warmth, weakness, general feeling of being unwell (malaise), chills, fatigue, thirst, skin redness (erythema), pain and inflammation of the vein at the infusion site (phlebitis). Uncommon(may affect up to 1 in 100)
• Bleeding disorder with bruising and easy bleeding (thrombocytopenia).
• Allergy (hypersensitivity).
• Anxiety, depression, hallucinations.
• Fainting (syncope), tremor, migraine.
• Blurred vision, eye irritation, eye pain.
• Irregular heartbeat (arrhythmia, extrasystoles).
• Pain in the legs caused by blood clots in a leg vein (deep vein thrombosis).
• Diarrhea with blood in the stool, rectal bleeding, heartburn or stomach pain, pain due to constipation, constipation, belching, difficulty swallowing, dry mouth, altered taste.
• Yellowing of the skin or whites of the eyes and/or itching (jaundice).
• Itching
• Painful muscle spasms, muscle spasms, muscle stiffness.
• Kidney pain, constant urge to urinate (vesical tenesmus), difficult or painful urination, urinary tract disorders. Rare(may affect up to 1 in 1,000)
• dizziness caused by inner ear disorders.
• Cough
• Inflammation of the lining of the rectum (proctitis).

The risk of bleeding is greater in patients who are also receiving antiplatelet agents, heparin or coumarin anticoagulants.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system available 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 Italia

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 label and on the
pack. The expiry date refers to the last day of that month.
This medicine does not require any particular storage conditions. Do not freeze.
Storage conditions after dilution
The chemical-physical stability during use has been demonstrated for 24 hours at 2-8°C.
From a microbiological point of view, the medicine must be used immediately. If not
used immediately, the duration and conditions of storage during use are under the
responsibility of the user and normally should not exceed 24 hours at 2 – 8°C
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Iloprost Zentiva Italia contains

• The active substance is iloprost. Each 0.5 ml vial of concentrate for solution for infusion contains 50 micrograms of iloprost (as iloprost trometamol). Each ml of concentrate for solution for infusion contains 100 micrograms of iloprost (as iloprost trometamol).
• The other ingredients are 96% ethanol, trometamol, sodium chloride, dilute hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Iloprost Zentiva Italia and contents of the pack
Clear and colourless solution, free from visible particles. Iloprost Zentiva Italia is supplied in transparent glass vials
of hydrolytic class I, with coloured identification rings: red, green in PVC blisters, in
cardboard box.
Each pack contains 1, 5 vials of 0.5 ml.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Marketing authorisation holder
Zentiva Italia Srl
Viale Bodio 37/b
20158 Milan

Manufacturer
Zentiva k.s.
U kabelovny130
102 37, Praha10 –Dolní Měcholupy
Czech Republic

This medicinal product is authorised in the Member States of the European Economic Area with the following
denominations:
Czech Republic Calovat
Italy Iloprost Zentiva Italia
Germany Iloprost Zentiva 100 Mikrogramm/ml Konzentrat zur Herstellung einer Infusionslösung
France Iloprost Zentiva 100 microgrammes/ml, solution à diluer pour perfusion
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The following information is intended exclusively for healthcare professionals
Instructions for handling
The ready-to-use infusion solution must be prepared immediately before use under aseptic conditions. The ready-to-use infusion solution must be prepared daily to ensure its
sterility.
Iloprost Zentiva Italia 100 micrograms/ml must be administered after dilution.
Due to possible interactions, no other medicinal products should be added to the ready-to-use infusion solution.
The ready-to-use solution must be used for a single patient and for a single infusion. The unused contents of the vial and the unused infusion solution must be discarded. Any unused medicinal product or waste material must be disposed of in accordance with local regulations.
If the ready-to-use infusion solution is not used immediately, the duration and conditions of
storage during use are the responsibility of the user. Normally it should not exceed
24 hours at 2 – 8°C.
If Iloprost Zentiva Italia 100 micrograms/ml comes into contact with the skin, the affected area should be
washed immediately with plenty of water or physiological saline
The procedure for preparing a ready-to-use infusion solution is described below based on
the infusion system used.

Use with an infusion pump
In general, the ready-to-use infusion solution should be administered intravenously with an
infusion pump.
The contents of a 0.5 ml vial of Iloprost Zentiva Italia 100 micrograms/ml (e.g. 50 μg of iloprost) must
be diluted using 250 ml of physiological saline or 5% glucose solution. The contents of the vial and
the diluent must be mixed thoroughly.
If dilution with 5% glucose solution is chosen, it should only be carried out in a
glass container.
The infusion rate required for this infusion solution (0.2 μg/mL) to achieve a dose in the range
between 0.5 and 2.0 ng/kg/min according to the scheme described in paragraph 3 of this leaflet must be
determined based on the individual patient's weight and as reported in Table 1.
Table 1: Infusion rate [ml/h] for different doses using an infusion pump.
Dose [ng/kg/min]
0,5 1,0 1,5 2,0
Infusion rate [ml/h]
40 6,0 12 18,0 24
50 7,5 15 22,5 30
60 9,0 18 27,0 36
70 10,5 21 31,5 42
80 12,0 24 36,0 48
90 13,5 27 40,5 54
100 15,0 30 45,0 60
110 16,5 33 49,5 66

Use with a syringe pump
Alternatively, a syringe pump with a 50 ml syringe can also be used for the infusion.
The contents of a 0.5 ml vial of Iloprost Zentiva Italia 100 micrograms/ml (e.g. 50 μg of iloprost) must
be diluted using 25 ml of physiological saline or 5% glucose solution. The contents of the vial and the
diluent must be mixed thoroughly.
The infusion rate required for this infusion solution (2.0 μg/mL) to achieve a dose in the range
Body weight
[kg]
between 0.5 and 2.0 ng/kg/min according to the scheme described in paragraph 3 of this leaflet must be
determined based on the individual patient's weight and as reported in Table 2.
Table 2: Infusion rate [ml/hour] for different doses using a syringe pump.
Dose (ng/kg/min)
0,5 1,0 1,5 2,0
Infusion rate (ml/hour)
40 0,60 1,2 1,80 2,4
50 0,75 1,5 2,25 3,0
60 0,90 1,8 2,70 3,6
70 1,05 2,1 3,15 4,2
80 1,20 2,4 3,60 4,8
90 1,35 2,7 4,05 5,4
100 1,50 3,0 4,50 6,0
110 1,65 3,3 4,95 6,6
Body weight
(kg)