Iloprost Teva

Package leaflet: information for the patient

Iloprost Teva 100 micrograms/ml concentrate for solution for infusion

iloprost
Generic medicinal product
Read this entire leaflet carefully before 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including any 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 using 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 Iloprost Teva is and what it is used for

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

• advanced thromboangiitis obliterans (Buerger's disease) with severe limb ischemia when revascularization surgery is not possible;
• severe peripheral arterial occlusive disease (PAOD), particularly in patients at risk of amputation when surgical or angioplasty procedures cannot be performed;
• severe Raynaud's phenomenon in patients who do not respond to other therapeutic measures.

2. What you should know before taking Iloprost Teva

Do not take Iloprost Teva:

• if you are allergic to iloprost or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or breastfeeding;
• if you have a condition for which the use of Iloprost Teva could increase the risk of bleeding (e.g., in case of active peptic ulcer, trauma, or intracranial bleeding);
• if you have severe coronary artery disease or unstable angina;
• if you have had a heart attack within the last 6 months;
• if you have heart failure;
• if you have severe arrhythmias (irregular heartbeats);
• if you have suspected pulmonary congestion (excess fluid in the lungs).

If you require urgent amputation (e.g., due to infected gangrene), surgical intervention
must not be delayed in favor of attempting treatment with Iloprost Teva.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Iloprost Teva.

• If you smoke, you are strongly advised to stop smoking.
• Inform your doctor if you have liver or kidney problems, as the dose of Iloprost Teva may need to be reduced.
• Inform your doctor if you have low blood pressure. Your doctor will pay particular attention to avoid further drops in blood pressure caused by Iloprost Teva. If you have heart disease, you will be closely monitored.
• Be cautious when standing up after administration of this medicine, as there is a risk of experiencing a sudden drop in blood pressure.
• Inform your doctor if you have had a stroke or transient ischemic attack (often called “TIA” or “mini-stroke”) within the last 3 months.

If undiluted Iloprost Teva is injected near a vein (paravascular injection), this may cause
local reactions at the injection site.
Iloprost Teva must not be ingested.
Avoid contact of Iloprost Teva with skin and eyes. In case of skin contact, Iloprost Teva
may cause persistent skin redness (erythema), without pain. If Iloprost Teva comes into contact
with skin or eyes, the affected area must be immediately rinsed with abundant water or
physiological saline solution.
In women, pregnancy must be ruled out 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
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any
other medicines.
Some medicines may interact with Iloprost Teva. In such cases, your doctor may need to adjust the
dose or discontinue treatment. It is particularly important that you inform 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 antagonists, vasodilators, or ACE inhibitors; Iloprost Teva may cause a further decrease in 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 nitrovasodilators [e.g., glyceryl trinitrate, isosorbide mononitrate, isosorbide dinitrate, or molsidomine]). Administration of Iloprost Teva together with any of these medicines may increase the risk of bleeding. If you experience bleeding, treatment with Iloprost Teva must be stopped.
• Medicines used to treat inflammation, such as steroids (corticosteroids). The effect of Iloprost Teva may be reduced.

Pregnancy and breastfeeding
Iloprost Teva must not be administered during pregnancy or while breastfeeding.
If you are pregnant or suspect you may be pregnant, inform your doctor immediately. You must
not take Iloprost Teva if you are pregnant.
If you are a woman of childbearing potential and could become pregnant, ensure you use a reliable
contraceptive method during treatment with Iloprost Teva.
Discontinue breastfeeding at the start of treatment with Iloprost Teva.
Iloprost Teva must not be used by women who are breastfeeding, as it is unknown whether the active substance 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 have no 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 only be administered in properly equipped hospital facilities or outpatient clinics and under close supervision.
After dilution, Iloprost Teva will be given by intravenous infusion. The infusion will last approximately 6 hours and will be administered once daily.
During the first 2–3 days of treatment, your doctor will determine the correct dose for you. During this period, you will be closely monitored for adverse effects such as headache, nausea, and low blood pressure. If any of these effects occur, the dose will be adjusted accordingly. If the adverse effects are severe, the infusion will be suspended.
Once your doctor has determined the correct dose for you, treatment will continue at this dose.
Treatment with Iloprost Teva may last up to a maximum of 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 lasting for several weeks.
Your doctor will inform you how long your treatment with Iloprost Teva should continue. Do not stop treatment prematurely.
If you are given more Iloprost Teva than you should
Symptoms of overdose include low blood pressure, headache, flushing (sudden redness of the face), nausea, vomiting, and diarrhoea.
Other possible symptoms include high blood pressure, slowed or rapid heartbeat, and pain in the limbs or back.
If you experience symptoms that may indicate 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, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The side effects observed most frequently are headache, flushing (sudden reddening 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 resolve quickly by reducing the dose.
The following serious side effects have been observed in patients treated with iloprost. Inform your doctor, pharmacist or nurse immediately if you notice any of these side effects, as some reported cases have been potentially fatal:
Common (may affect up to 1 in 10 people)

• increased heart rate
• chest pain or discomfort caused by insufficient blood flow to the heart (angina pectoris)
• low blood pressure
• difficulty breathing (dyspnoea).

Uncommon (may affect up to 1 in 100 people)

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

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
• confusion
• dizziness/vertigo
• tingling, pulsating sensation, increased sensitivity to pain or touch, burning sensation
• restlessness, agitation
• sedation
• somnolence
• slow heart rate
• high blood pressure
• diarrhoea
• abdominal discomfort, stomach ache
• jaw pain, trismus
• muscle pain, joint pain
• pain
• fever/increased body temperature
• feeling of warmth
• weakness, feeling unwell
• chills
• fatigue, tiredness
• thirst
• skin redness, pain and inflammation of the vein at the infusion site (which may cause a red, streak-like rash along the course of the vein used for infusion).

Uncommon (may affect up to 1 in 100 people)

• reduced number of platelets in the blood, increasing 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)
• diarrhoea with blood in stools, rectal bleeding
• indigestion
• feeling of constant need to defecate
• constipation
• belching
• difficulty swallowing
• dry mouth, altered taste
• jaundice (which may cause yellowing of the skin or whites of the eyes)
• itching
• tetany (painful attack of muscle spasms)
• muscle spasms
• muscle stiffness
• kidney pain
• sensation 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 with the inner ear that may cause dizziness/vertigo)
• cough
• inflammation of the rectum.

Iloprost Teva may trigger angina pectoris (chest pain or discomfort), especially in patients with heart disease.
The risk of bleeding is higher in patients receiving Iloprost Teva together with other antiplatelet agents, heparin or vitamin K antagonists (see “Other medicines and Iloprost Teva”).
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system available at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects 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 label of the vial and on the carton after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C when diluted with 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 medicine should be used immediately. If not used immediately, the duration and conditions of in-use storage are under the responsibility of the user.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Iloprost Teva contains

• The active substance is iloprost.
• One ml contains 100 micrograms of iloprost.
• The other components are trometamol, ethanol 96%, 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, 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
TEVA B.V.
Swensweg 5,
2031 GA Haarlem
The 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 European Economic Area Member States under the following names:
France: Iloprost Teva 100 microgrammes/mL, solution to be diluted for infusion
Germany: Iloprost Rathiopharm 100 micrograms/ml concentrate for the preparation of an infusion solution
Italy: Iloprost Teva 100 microgrammi/ml concentrato per soluzione per infusione
The Netherlands: Iloprost Teva 100 microgram/ml concentrate for infusion solution

The following information is intended for healthcare professionals only
Dosage and method of administration
After dilution, Iloprost Teva must be administered by intravenous infusion over 6 hours per day, via a peripheral vein or a central venous catheter.
During the first 2–3 days of treatment, the dose tolerated by the individual patient must be determined. Initial treatment should start at an infusion rate of 0.5 ng/kg/min for 30 minutes. The dose should then be increased in increments of 0.5 ng/kg/min at approximately 30-minute intervals, up to a maximum of 2.0 ng/kg/min. The exact infusion rate must be calculated based on body weight so that it falls within the range of 0.5–2.0 ng/kg/min (see tables below for use with infusion pump or syringe pump).
Blood pressure and heart rate must be measured at the beginning of each infusion and after each dose increase.
If adverse reactions such as headache, nausea or hypotension occur, the infusion rate must be reduced until the tolerated dose is reached. In case of severe adverse reactions, administration must be suspended.
Treatment should continue (usually for 4 weeks) at the individually determined tolerated dose established during the first 2–3 days.
Depending on the infusion technique, there are two different ways to dilute the contents of one vial. One of these dilutions is 10 times less concentrated than the other (0.2 mcg/ml vs. 2 mcg/ml) and must be administered only using an infusion pump. In contrast, the more concentrated solution must be administered only using a syringe pump.
The vial contents and diluent must be thoroughly mixed.

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 using an infusion pump (e.g. Infusomat®).
The contents of one 0.5 ml vial of Iloprost Teva (50 micrograms) must be diluted with sterile physiological saline or 5% glucose solution to a final volume of 250 ml.
The contents of one 1.0 ml vial of Iloprost Teva (100 micrograms) must be diluted with sterile physiological saline or 5% glucose solution to a final volume of 500 ml.
After reconstitution, the solution must be clear, colourless and free of 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 table below to achieve a dose within the range of 0.5–2.0 ng/kg/min.
The following table can be used to calculate the infusion rate based on the patient's weight and the required dose to be infused. To determine 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 need to be interpolated to match the patient's actual body weight, and the infusion rate adjusted accordingly to achieve 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 may also be used.
The contents of one 0.5 ml vial of Iloprost Teva (50 micrograms) must be diluted with sterile physiological saline or 5% glucose solution to a final volume of 25 ml.
The contents of one 1.0 ml vial of Iloprost Teva (100 micrograms) must be diluted with sterile physiological saline or 5% glucose solution to a final volume of 50 ml.
After reconstitution, the solution must be clear, colourless, and free of 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 achieve a dose within the range of 0.5 to 2.0 ng/kg/min.
The following table can be used to calculate the infusion rate according to the patient's body weight and the dose to be infused. To determine 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 need to be calculated to adjust for the patient's actual body weight, and the infusion rate should then be adapted accordingly to achieve the target dose in ng/kg/min.

The duration of treatment may extend up to a maximum of 4 weeks. In cases of Raynaud's phenomenon, shorter treatment periods (3–5 days) are often sufficient to achieve improvement lasting for several weeks.

Pregnancy and breastfeeding

Pregnancy
Data on the use of iloprost during pregnancy are limited. Preclinical studies have shown fetotoxicity in rats, but not in rabbits or monkeys.
Since the potential risk of therapeutic use of iloprost during pregnancy is unknown, women of childbearing potential must use an effective contraceptive method during treatment.

Breastfeeding
It is not known whether iloprost is excreted in human breast milk. Since minimal amounts of the drug are excreted in rat milk, Iloprost Teva must not be administered to women who are breastfeeding.

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

Instructions for use and handling
Iloprost Teva may only be used after dilution. Due to the risk of pharmaceutical interactions, no other medicinal product must 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 of the product with the skin or eyes.
Oral ingestion and contact with mucous membranes must be avoided. In case of skin contact, iloprost may cause prolonged painless erythema. In the event of contact with skin or eyes, the affected area must be immediately washed with abundant water or physiological saline solution.