ILOPROST 100 MICROGRAMMI/ML Koncentrat do sporządzania roztworu infuzyjnego

Treść ulotki

1. Iloprost Teva 100 micrograms/ml concentrate for solution for infusion
   1. What is Iloprost Teva and what is it used for
   2. What you need to know before you take Iloprost Teva
   3. How to use Iloprost Teva
   4. Possible side effects
   5. How to store Iloprost Teva
   6. Contents of the pack and other information

Iloprost Teva 100 micrograms/ml concentrate for solution for infusion

iloprost

Equivalent medicinal product

Read this leaflet carefully before you start to use 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, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

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

Iloprost Teva belongs to a group of medicines called antiplatelet agents.
Iloprost Teva is used to treat the following conditions:

• obliterating thromboangiitis (Buerger's disease) in an advanced stage with severe limb ischemia in cases where revascularization surgery cannot be performed;
• severe peripheral obliterating arteriopathy (POA), particularly in patients at risk of amputation in whom surgical or angioplasty intervention is not possible;
• severe Raynaud's phenomenon and in patients who do not respond to other therapeutic measures.

2. What you need to know before you take Iloprost Teva

Do not take Iloprost Teva:

• 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;
• if you suffer from a condition for which the use of Iloprost Teva could increase the risk of bleeding (for example, in case of active peptic ulcer, trauma or bleeding inside the skull);
• if you suffer from severe coronary artery disease or unstable angina;
• if you have had a heart attack in the last 6 months;
• if you suffer from heart failure;
• if you suffer from severe arrhythmias (irregular heartbeats);
• if you suffer from suspected pulmonary congestion (excess fluid in the lungs).

If you need urgent amputation (e.g. in case of infected gangrene), the surgical intervention should not be postponed in favour of an attempt to treat with Iloprost Teva.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Iloprost Teva.

• If you smoke, it is strongly recommended that you quit smoking.
• Tell your doctor if you have liver or kidney problems, as the dose of Iloprost Teva may need to be reduced.
• Tell your doctor if you suffer from low blood pressure. Your doctor will pay particular attention to avoid Iloprost Teva causing further drops in blood pressure. If you suffer from heart disease, you will be carefully monitored.
• Be careful when getting up after the administration of this medicine, as there is a risk of experiencing a sudden drop in blood pressure.
• Tell your doctor if you have had a stroke or a transient ischemic attack (often called “TIA” or “mini-stroke”) in the last 3 months.

If Iloprost Teva, undiluted, is injected near a vein (perivasal injection), this can cause local changes at the injection site.
Iloprost Teva must not be swallowed.
Avoid getting Iloprost Teva on your skin and eyes. If Iloprost Teva comes into contact with the skin, it can cause a persistent redness of the skin (erythema), without pain. If Iloprost Teva comes into contact with the skin or eyes, the affected area should be washed immediately with plenty of water or saline solution.
In women, the possibility of pregnancy must be excluded before starting treatment.

Children and adolescents
The safety and efficacy of Iloprost Teva in children and adolescents have not yet been established. No data are available.

Other medicines and Iloprost Teva
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Some medicines can interact with Iloprost Teva. In these cases, your doctor may need to adjust the dose or stop the treatment. It is particularly important that you tell your doctor if you are taking any of the following medicines:

• Medicines used to treat high blood pressure or heart disease, such as beta-blockers, calcium channel blockers, vasodilators or ACE inhibitors; Iloprost Teva may result in a further lowering of blood pressure.
• Medicines including anticoagulants (such as heparin or coumarin-type anticoagulants) used to thin the blood, antiplatelet agents (such as acetylsalicylic acid, non-steroidal anti-inflammatory drugs, phosphodiesterase inhibitors [e.g. dipyridamole] and nitro-vasodilators [e.g. glyceryl trinitrate, isosorbide mononitrate, isosorbide dinitrate or molsidomine]). The administration of Iloprost Teva in conjunction with any of these medicines may increase the risk of bleeding. If you should bleed, treatment with Iloprost Teva should be stopped.
• Medicines to treat inflammation, such as steroids (corticosteroids). It is possible that the effect of Iloprost Teva may be reduced.

Pregnancy and breastfeeding
Iloprost Teva should not be administered during pregnancy or while breastfeeding.

If you are pregnant or suspect you may be pregnanttell your doctor immediately. You should not take Iloprost Teva if you are pregnant.

If you are a woman of childbearing potential and could become pregnant, make sure to use a reliable method of contraception during treatment with Iloprost Teva.

Stop breastfeeding at the beginning of treatment with Iloprost Teva.
Iloprost Teva should not be used by women who are breastfeeding, as it is not known whether the active ingredient passes into breast milk.

Iloprost Teva contains ethanol
This medicine contains 8.10 mg of alcohol (ethanol) in each 1 ml vial of concentrate and 4.05 mg in each 0.5 ml vial of concentrate. The amount in 1 ml of this medicine is equivalent to less than 1 ml of beer or wine. The small amount of alcohol contained in this medicine will not have significant effects.

Iloprost Teva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to use Iloprost Teva

Iloprost Teva will be administered to you by a healthcare professional.
Iloprost Teva must be administered only in hospital facilities or adequately
equipped outpatient clinics and under strict supervision.
After dilution, Iloprost Teva will be administered by infusion into a vein. The infusion
will last approximately 6 hours and will be administered once a day.
During the first 2-3 days of treatment, the doctor will determine the correct dose for you. During this period, you
will be closely monitored for the detection of undesirable effects such as headache, nausea and
low blood pressure. If any of these effects occur, the dose will be adjusted accordingly. If
undesirable effects are severe, the infusion will be stopped.
After the doctor has determined the correct dose for you, treatment will continue at this dose.
Treatment with Iloprost Teva can last up to 4 weeks.
However, when Iloprost Teva is used to treat Raynaud's phenomenon, shorter treatment periods (3-5 days) are often sufficient
to achieve improvement for several weeks.
The doctor will tell you how long to continue treatment with Iloprost Teva. Do not stop treatment
before the time.

If you are given more Iloprost Teva than you should
Symptoms of overdose are decreased blood pressure, 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 Teva, contact
your doctor, pharmacist or nurse immediately.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects observed most frequently are headache, flushing (sudden redness of the face), nausea, vomiting and excessive sweating (hyperhidrosis). These side effects are likely to occur at the beginning of treatment, during dose adjustment. However, they usually disappear quickly by reducing the dose.
In patients treated with iloprost, the following serious side effects have been observed. Inform your doctor, pharmacist or nurse immediately if you notice the occurrence of any of these side effects, as some reported cases have proven to be potentially life-threatening:

Common(may affect up to 1 in 10 people)

• acceleration of the heartbeat
• chest pain/discomfort caused by insufficient blood flow to the heart (angina pectoris)
• low blood pressure
• difficulty breathing (dyspnea).

Uncommon(may affect up to 1 in 100 people)

• convulsions
• heart attack
• heart failure
• stroke
• breathing problems or chest pain caused by the presence of blood clots in the lungs (pulmonary embolism)
• asthma
• fluid accumulation in the lungs (pulmonary edema).

Other possible side effects are:

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

• headache
• flushing
• nausea
• vomiting
• excessive sweating.

Common(may affect up to 1 in 10 people)

• loss of appetite
• apathy
• confusional state
• dizziness/vertigo
• tingling, pulsating sensation, increased sensitivity to pain or touch, burning sensation
• restlessness, agitation
• sedation
• drowsiness
• slowed heartbeat
• high blood pressure
• diarrhea
• abdominal discomfort, stomach pain
• jaw pain, trismus
• muscle pain, joint pain
• pain
• fever/increased body temperature
• feeling of warmth
• weakness, feeling unwell
• chills
• tiredness, fatigue
• thirst
• redness of the skin, pain and inflammation of the vein at the infusion site (which can cause a reddish, streaky rash on the skin along the course of the vein used for the infusion).

Uncommon(may affect up to 1 in 100 people)

• reduced number of platelets in the blood, which increases the risk of bleeding or bruising
• allergic reaction
• anxiety, depression, hallucinations
• fainting
• tremor
• migraine
• blurred vision
• eye irritation
• eye pain
• irregular heartbeat
• reduced blood supply to the brain
• blood clots in a vein (deep vein thrombosis)
• diarrhea with blood in the stool, rectal bleeding
• indigestion
• feeling of constant need to defecate
• constipation
• belching
• difficulty swallowing
• dry mouth, altered taste
• jaundice (which can cause yellowing of the skin or whites of the eyes)
• itching
• tetany (painful attack of muscle spasms)
• muscle spasms
• muscle stiffness
• kidney pain
• feeling of incomplete bladder emptying
• abnormal urine
• pain (or difficulty) during urination
• urinary tract disorders.

Rare(may affect up to 1 in 1,000 people)

• vestibular disorder (a problem of the inner ear that can cause dizziness/vertigo)
• cough
• rectal inflammation.

Iloprost Teva can trigger angina pectoris (chest pain/discomfort), especially in patients who suffer from heart disease.
The risk of bleeding is greater in patients to whom Iloprost Teva is administered in conjunction with other antiplatelet agents, heparin or coumarin anticoagulants (see “Other medicines and Iloprost Teva”).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. 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 Teva

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 the pack after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any particular storage conditions.
The chemical-physical stability during use has been demonstrated for 24 hours at 25°C when diluted with
0.9% sodium chloride solution or 5% dextrose.
From a microbiological point of view, unless the dilution method excludes the risk of
microbial contamination, 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.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that you no
longer use. This will help protect the environment.

6. Contents of the pack and other information

What Iloprost Teva contains

• The active ingredient is iloprost.
• 1 ml contains 100 micrograms of iloprost.
• The other components are trometamol, 96% ethanol, sodium chloride, hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Iloprost Teva and contents of the pack
Iloprost Teva is supplied as a clear, colourless and particle-free concentrate for infusion solution.
Each vial contains 0.5 ml or 1.0 ml of concentrate for infusion solution.
Each pack contains 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
TEVA B.V.
Swensweg 5,
2031 GA Haarlem
Netherlands

Manufacturer
RAFARM S.A.
Thesi Pousi-Xatzi, Agiou Louka, 19002 Paiania Attiki - Greece
Merckle GmbH
Ludwig-Merckle-Strasse 3, 89143 Blaubeuren - Germany
Actavis Italy S.P.A.
Via Pasteur 10, Nerviano, 20014 Milano - Italy

This medicinal product is authorised in the Member States of the European Economic Area under the following
denominations:
France: Iloprost Teva 100 microgrammes/mL, solution à diluer pour perfusion
Germany: Iloprost Rathiopharm 100mikrogramm/ml konzentrat zur herstellung einer infusionslosung
Italy: Iloprost Teva 100 microgrammi/ml concentrato per soluzione per infusione
Netherlands: Iloprost Teva 100 microgram/ml concentraat voor oplossing voor infusie
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The following information is intended for healthcare professionals only
Dosage and method of administration
After dilution, Iloprost Teva must be administered by intravenous infusion for 6 hours per
day, into a peripheral vein or via a catheter into a central vein.
In the first 2-3 days of treatment, the dose tolerated by the individual patient must be determined. Initial treatment must be started at an infusion rate of 0.5 ng/kg/min for 30 minutes. The dose must then be
increased in increments of 0.5 ng/kg/min at intervals of approximately 30 minutes, up to a maximum of 2.0
ng/kg/min. The exact infusion rate must be calculated based on body weight, so that it is
within the range of 0.5-2.0 ng/kg/min (see the tables below for use with an infusion pump or
for use with a syringe pump).
At the beginning of each infusion and after each dose increase, arterial pressure
and heart rate must be measured.
If adverse reactions such as headache, nausea or a decrease in blood pressure occur, the infusion rate
must be reduced until the tolerated dose is reached. In the event of severe adverse reactions, administration must be stopped.
Treatment should continue (usually for 4 weeks) at the tolerated dose identified in the first 2-3 days.
Depending on the infusion technique, there are two different ways to dilute the contents of a vial. One of
these two dilutions is 10 times less concentrated than the other (0.2 mcg/ml versus 2 mcg/ml) and can be
administered only with an infusion pump. Conversely, the more concentrated solution can be
administered only with a syringe pump.
The contents of the vial and the diluent must be mixed thoroughly.

Infusion rate [ml/hour] for different doses using an infusion pump
In general, the ready-to-use infusion solution (0.2 mcg/ml) must be administered intravenously with an
infusion pump (e.g. Infusomat®).
The contents of a 0.5 ml vial of Iloprost Teva (50 micrograms) must be diluted with sterile saline or 5% dextrose solution to a final volume of 250 ml.
The contents of a 1.0 ml vial of Iloprost Teva (100 micrograms) must be diluted with sterile saline or 5% dextrose solution to a final volume of 500 ml.
After reconstitution, the solution must be clear, colourless, and free from visible particles.
If Iloprost Teva is to be administered at a concentration of 0.2 mcg/ml, the required infusion rate
must be determined according to the scheme below, in order to obtain a dose in the range
between 0.5 and 2.0 ng/kg/min.
The following table can be used to calculate the infusion rate corresponding to the patient's weight and the dose to be infused. To establish the correct infusion rate (ml/hour), identify the
patient's actual body weight and the required dose (ng/kg/min) in the table below. Intermediate values may be
necessary to adapt them to the patient's actual body weight and then adjust
the infusion rate to the target dose in ng/kg/min.

Infusion rate [ml/hour] for different doses using a syringe pump
A syringe pump (e.g. Perfusor®) with a 50 ml syringe can also be used.
The contents of a 0.5 ml vial of Iloprost Teva (50 micrograms) must be diluted with sterile saline or 5% dextrose solution to a final volume of 25 ml.
The contents of a 1.0 ml vial of Iloprost Teva (100 micrograms) must be diluted with sterile saline or 5% dextrose solution to a final volume of 50 ml.
After reconstitution, the solution must be clear, colourless, and free from visible particles.
If Iloprost Teva is to be administered at a concentration of 2 mcg/ml, the required infusion rate
must be determined according to the scheme below, in order to obtain a dose in the range between
0.5 and 2.0 ng/kg/min.
The following table can be used to calculate the infusion rate corresponding to the patient's weight and the dose to be infused. To establish the correct infusion rate (ml/hour), identify the
patient's actual body weight and the required dose (ng/kg/min) in the table below. Intermediate values may be
necessary to adapt them to the patient's actual body weight and then adjust
the infusion rate to the target dose in ng/kg/min.
The duration of treatment can last up to 4 weeks. In the case of Raynaud's phenomenon,
shorter periods of treatment (3-5 days) are often sufficient to obtain improvement for several
weeks.

Pregnancy and breastfeeding
Iloprost Teva should not be administered during pregnancy or breastfeeding.
Pregnancy
Data relating to the use of iloprost in pregnancy are limited. Preclinical studies have shown fetotoxicity
in the rat, but not in the rabbit or monkey.

Since the potential risk of therapeutic use of iloprost in pregnancy is not known, women of childbearing potential
must use an effective method of contraception during treatment.
Breastfeeding
It is not known whether iloprost is excreted in breast milk. Since minimal amounts of the drug are excreted
in rat milk, Iloprost Teva should not be administered to women who are breastfeeding.

Shelf life

Unopened vial:5 years
Chemical and physical stability during use has been demonstrated for 24 hours at 25°C when diluted with a
0.9% sodium chloride solution or 5% dextrose solution.
From a microbiological point of view, unless the dilution method excludes the risk of
microbial contamination, the medicinal product must be used immediately. If not used
immediately, the storage times and conditions during use are the responsibility of the user.

Instructions for use and handling
Iloprost Teva can only be used after dilution. Due to the risk of drug interactions, no other medicinal products can be added to the prepared infusion.
The infusion solution must be prepared daily at the time of use,
to ensure sterility.

Handling
Appropriate precautions must be taken to avoid contact with the skin or
eyes.
Oral ingestion and contact with mucous membranes must be avoided. If it comes into contact with the skin, iloprost
can cause painless, long-lasting erythema. In the event of contact with the skin or eyes, the affected area must be washed immediately with plenty of water or saline solution.