Ilomedin 50 micrograms/0.5 ml, concentrate for solution for infusion

Patient Information Leaflet

Introduction

PACKAGE LEAFLET: Information for the user

Ilomedin 50 micrograms / 0.5 ml, concentrate for solution for infusion

iloprost trometamol

Package leaflet

1. What Ilomedin is and what it is used for

2. What you need to know before using Ilomedin

3. How to use Ilomedin

4. Possible side effects

5. How to store Ilomedin

6. Contents of the pack and other information

1. What Ilomedin is and what it is used for

Ilomedin belongs to the group of medicinal products known as anti-thrombotic agents that inhibit platelet aggregation, excluding heparin.

Ilomedin is a prostacyclin analogue indicated for the treatment of:

Advanced thromboangiitis obliterans (Buerger's disease) with severe limb ischaemia in cases where revascularization is not indicated.

Patients with severe occlusive peripheral arterial disease, particularly in those cases at risk of amputation and in whom surgery or angioplasty is not feasible.

Patients with severe and disabling Raynaud's phenomenon unresponsive to other therapeutic measures.

2. What you need to know before starting to use Ilomedin

Do not use Ilomedin

• If you are allergic to iloprost or to any of the other components of this medicine (listed in section 6).

• If you are pregnant or breastfeeding.

• In situations where the effects of Ilomedin may increase the risk of bleeding (e.g., active peptic ulcers, trauma, intracranial hemorrhage).

• If you suffer from severe coronary heart disease or unstable angina; myocardial infarction within the last six months; acute or chronic congestive heart failure (NYHA classes II-IV); prognostically significant arrhythmias; suspected pulmonary congestion.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Ilomedin.

• If you require urgent amputation (e.g., in case of infected gangrene), surgical intervention must not be delayed.

• If you smoke, you must be strongly advised to stop smoking.

• If you have low blood pressure, special care must be taken to avoid further hypotension; and if you have significant heart disease, you must be closely monitored.

• You should be aware of the possibility of hypotension occurring when moving from a lying to a standing position after completion of the infusion.

• You should know that paravascular perfusion of the undiluted Ilomedin solution may cause local reactions at the injection site.

Consult your doctor, even if any of the above-mentioned conditions ever applied to you.

Other medicines and Ilomedin

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Certain medicines may interact, and in such cases it may be necessary to adjust the dose or discontinue treatment with one of the medicines. It is especially important that you inform your doctor if you are taking any of the following medicines.

If you are being treated with heparin or coumarin anticoagulants, treatment with Ilomedin may increase the risk of bleeding. If this occurs, infusion of this medicine must be stopped.

If you are being treated with other platelet aggregation inhibitors (acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, phosphodiesterase inhibitors, and nitrate vasodilators – e.g., molsidomine), administration of Ilomedin may have an additive or synergistic effect on platelet function.

In addition, you should be aware that pharmacological studies have shown that iloprost has an additive effect on the antihypertensive activity of beta-blockers, calcium antagonists, and vasodilators, as well as a potentiating effect on the antihypertensive activity of angiotensin-converting enzyme inhibitors (ACE inhibitors). If significant hypotension occurs, it can be corrected by reducing the dose of iloprost.

Ilomedin contains ethanol

This medicine contains 4.05 mg of alcohol (ethanol) per ampoule. The amount of this medicine is equivalent to less than 1 ml of beer or wine. The small amount of alcohol contained in this medicine does not produce any noticeable effect.

Ilomedin contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ampoule; hence, it is essentially “sodium-free”.

Pregnancy, lactation and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Ilomedin must not be administered during pregnancy. The potential risk of using iloprost therapeutically during pregnancy is unknown; therefore, if you are of childbearing age, you must use an effective method of contraception during treatment.

Ilomedin must not be administered during breastfeeding. It is unknown whether iloprost passes into breast milk.

Driving and use of machines

Not applicable.

3. How to use Ilomedin

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor again.

This medicine should only be used in properly equipped hospitals and healthcare centers and under strict monitoring.

The infusion solution must be prepared daily to ensure sterility.

This medicine is administered daily for 6 hours as an intravenous infusion, after dilution, through a central venous catheter or a peripheral vein. The dose is adjusted according to individual tolerance within the range of 0.5 - 2.0 ng of iloprost/kg body weight/min. The exact infusion rate must be calculated based on body weight (for further information, see section “6. Additional information of interest for the physician supervising the treatment”).

During the first 2 - 3 days, the dose you can tolerate will be established. If side effects such as headache and nausea occur, or an undesirable drop in blood pressure, the infusion rate will be reduced until the tolerated dose is determined. If adverse effects are severe, the infusion must be stopped. Subsequently, treatment should continue (usually for 4 weeks) at the tolerated dose established during the first 2 - 3 days.

Blood pressure and heart rate should be recorded at the beginning of the infusion and after each dose increase.

The duration of treatment is up to 4 weeks. In the case of Raynaud's phenomenon (episodes of pallor followed by cyanosis and redness of the extremities related to cold or emotional stress), shorter treatment periods (3 to 5 days) are often sufficient to achieve improvement lasting for several weeks.

Consideration should be given if you have renal insufficiency requiring dialysis or hepatic cirrhosis, as in these conditions the elimination of iloprost is reduced and the dose should be decreased (e.g., to half the recommended dose).

Continuous infusion over several days is not recommended due to the possibility of developing immunization against platelet effects or a rebound effect with platelet hyperaggregation at the end of treatment, although no clinical complications associated with these phenomena have been reported.

Your doctor will determine the duration of your Ilomedin treatment. Do not stop treatment prematurely.

If you use more Ilomedin than you should

You may experience the following symptoms: marked facial flushing, severe headache, nausea, vomiting and diarrhea, and possibly pain in the limbs or back. Decreased or increased blood pressure, bradycardia (decrease below normal heart rate) or tachycardia (increase above normal heart rate).

If symptoms indicate that you have received more Ilomedin than appropriate, Ilomedin infusion should be stopped and symptomatic treatment administered. There is no known specific antidote.

In case of overdose or accidental ingestion, contact the Toxicology Information Service; Telephone 91 562 04 20.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The most frequently observed adverse effects in patients treated with Iloprost (may affect 1 or more out of every 10 patients) are headache, flushing (redness of the face), hyperhidrosis (sweating), and gastrointestinal symptoms such as nausea (feeling sick) and vomiting.

These are expected to occur at the beginning of treatment while the dose is being adjusted and the best tolerated dose is being established. However, all these adverse effects usually disappear rapidly with dose reduction.

The most serious adverse reactions in which fatal outcomes or life-threatening events have been observed in patients treated with Iloprost were:

• stroke (cerebrovascular accident)
• myocardial infarction (heart attack)
• pulmonary embolism (difficulty breathing or chest pain on inspiration caused by a blood clot in the lung)
• cardiac failure (heart failure)
• seizures
• hypotension (abnormally low blood pressure)
• tachycardia (increased heart rate)
• asthma
• angina pectoris (chest pain or pressure caused by insufficient blood flow to the heart)
• dyspnea (difficulty breathing)
• pulmonary edema (difficulty breathing or coughing up blood caused by fluid accumulation in the lungs)

Another group of adverse effects relates to local reactions at the infusion site. For example, redness and pain at the infusion site or cutaneous vasodilation causing a linear erythema (redness) along the infused vein may occur.

The possible adverse effects are listed below by frequency.

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

• headache
• flushing (facial redness)
• nausea (feeling sick)
• vomiting
• hyperhidrosis (sweating)

Common (may affect 1 to 10 patients in 100)

• decreased appetite
• apathy
• confusion
• dizziness / vertigo
• paresthesia (numbness and tingling) / pulsatile sensation / hyperesthesia (increased sensitivity to pain or touch) / burning sensation
• restlessness / agitation
• sedation
• somnolence
• tachycardia (increased heart rate)
• bradycardia (decreased heart rate)
• angina pectoris (chest pain or pressure caused by insufficient blood flow to the heart)
• hypotension (abnormally low blood pressure)
• increased blood pressure
• dyspnea (difficulty breathing)
• diarrhea
• abdominal discomfort / abdominal pain
• jaw pain / trismus (jaw spasms)
• myalgia (muscle pain) / arthralgia (joint pain)
• pain
• fever / increased body temperature
• sensation of heat
• asthenia (weakness) / malaise
• chills
• fatigue / tiredness
• thirst
• erythema, pain and phlebitis at the infusion site (inflammation of the vein)

Uncommon (may affect 1 to 10 patients in 1,000)

• thrombocytopenia (a blood disorder characterized by easy bruising or bleeding)
• hypersensitivity (allergy)
• anxiety, depression, hallucinations
• seizures
• syncope (brief loss of consciousness)
• tremor
• migraine
• blurred vision
• eye irritation
• eye pain
• myocardial infarction (heart attack)
• cardiac failure (heart failure)
• arrhythmia / extrasystoles (irregular heartbeat)
• stroke / cerebral ischemia (cerebrovascular accident)
• pulmonary embolism (difficulty breathing or chest pain on inspiration caused by a blood clot in the lung)
• deep vein thrombosis (formation of a clot and its release into the bloodstream)
• asthma
• pulmonary edema (abnormal accumulation of fluid in the lungs)
• hemorrhagic diarrhea (diarrhea with blood) / rectal hemorrhage (bleeding)
• dyspepsia (stomach burning or pain)
• rectal tenesmus (pain due to constipation)
• constipation
• belching
• dysphagia (difficulty swallowing)
• dry mouth / dysgeusia (altered sense of taste)
• jaundice (yellowing of the skin or whites of the eyes and/or itching due to liver disorder)
• pruritus (itching)
• tetany (painful muscle spasm attack) / muscle spasms
• hypertonia (increased muscle tone)
• kidney pain
• vesical tenesmus (persistent urge to urinate)
• urinary disorders
• dysuria (pain or difficulty urinating)
• urinary tract disorders

Rare (may affect 1 to 10 patients in 10,000)

• vestibular disorder (dizziness caused by inner ear disturbance)
• cough
• proctitis (inflammation of the rectum)

Iloprost may cause chest pain or pressure due to angina pectoris, especially in patients with coronary insufficiency.

The risk of bleeding increases if you are receiving concomitant treatment with platelet aggregation inhibitors, heparin, or coumarin anticoagulants.

If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Pharmaceutical Precautions for Ilomedin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their containers. This helps protect the environment.

6. Contents of the pack and other information

Composition of Ilomedin

• The active substance is iloprost.
• The other components are: trometamol, ethanol, hydrochloric acid, sodium chloride, water for injections.

Appearance of the product and contents of the pack

Ilomedin is a clear, particle-free solution. One ampoule contains 0.5 ml of solution.

Marketing Authorization Holder:

Bayer Hispania, S.L.
Av. Baix Llobregat 3-5
08970 – Sant Joan Despí (Barcelona)
Spain

Manufacturer:

Berlimed, S.A
Francisco Alonso, s/n. Polígono Industrial Sta. Rosa.
28806 - Alcalá de Henares
Spain

Date of the most recent review of this product information: January 2014

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only.

Posology and method of administration

Ilomedin is administered daily for 6 hours as an intravenous infusion, after dilution, via a central venous catheter or a peripheral vein. During the first 2–3 days, the dose tolerated by the patient is established. To this end, treatment should be initiated at an infusion rate of 0.5 ng/kg/min for 30 minutes. Subsequently, the dose should be increased by 0.5 ng/kg/min approximately every 30 minutes, up to a maximum of 2.0 ng/kg/min. The exact infusion rate must be calculated based on body weight to achieve an infusion rate within the range of 0.5–2.0 ng/kg/min (for use with an infusion pump or syringe driver, see tables below).

Blood pressure and heart rate should be monitored at the beginning of the infusion and after each dose increase.

Infusion rates (ml/h) for different doses for administration via infusion pump

In general, the ready-to-use infusion solution is administered intravenously using an infusion pump (e.g., Infusomat®). For this purpose, the contents of one 0.5 ml ampoule of Ilomedin are diluted with 250 ml of sterile physiological saline or 5% glucose solution. The contents of the ampoule and the diluent must be thoroughly mixed. If a concentration of Ilomedin of 2 µg/ml is to be administered, the required infusion rate should be established according to the previously described scheme to achieve a dose within the range of 0.5–2.0 ng/kg/min.

(To determine the infusion rate, interpolate and match the patient's body weight with the desired dose in ng/kg/min).

Infusion rates (ml/h) for different doses for administration using a syringe pump

A syringe pump may also be used with a 50 ml syringe (e.g., Perfusor®). In this case, the contents of a 0.5 ml ampoule of Ilomedin are diluted with 25 ml of sterile physiological saline or 5% glucose solution. The contents of the ampoule and the diluent must be completely mixed. If an Ilomedin concentration of 2 µg/ml is to be administered, the required infusion rate must be determined according to the previously described scheme in order to achieve a dose within the range of 0.5 – 2.0 ng/kg/min.

To establish the infusion rate, interpolate and match the patient's body weight with the desired dose in ng/kg/min.

The duration of treatment is up to 4 weeks. In the case of Raynaud's phenomenon, shorter treatment periods (3 to 5 days) are often sufficient to achieve improvement lasting for several weeks.

Pregnancy and lactation

• Pregnancy

Ilomedin must not be administered during pregnancy. There are insufficient data regarding the use of iloprost in pregnant women. Preclinical studies have shown evidence of fetotoxicity in rats, but not in rabbits or monkeys.

• Lactation

Since extremely low amounts of iloprost pass into breast milk in rats, iloprost must not be administered to women who are breastfeeding.

Incompatibilities

This medicinal product must not be mixed, nor must any other substance be added to the ready-to-use infusion solution.

Shelf life

4 years.

Instructions for use and handling

Ilomedin must only be used after dilution. Due to the possibility of interactions, no other substance should be added to the ready-to-use infusion solution.

The ready-to-use infusion solution must be prepared each day prior to administration to ensure sterility.

• Handling

Oral ingestion and contact with mucous membranes must be avoided.

In case of skin contact, iloprost may cause a long-lasting, painless erythema. Therefore, appropriate precautions should be taken to avoid contact of iloprost with the skin. If such contact occurs, the affected area must be immediately washed with abundant water or physiological saline solution.