PROSPECTO: Information for the user

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

iloprost trometamol

1.What Ilomedin is and for what it is used.

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

3.How to use Ilomedin.

4.Possible adverse effects.

1. Storage of Ilomedin.

6. Contents of the pack and additional information

Ilomedin belongs to a group of medications known as antithrombotic agents that inhibit platelet aggregation, excluding heparin.

Ilomedin is a prostacyclin analog indicated for the treatment of:

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

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

Patients with severe and debilitating Raynaud's phenomenon who do not respond to other therapeutic measures.

No use Ilomedin

• If you are allergic to iloprost or any of the other components of this medication (including those 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 have severe coronary heart disease or unstable angina; myocardial infarction in the last six months; acute or chronic congestive heart failure (NYHA classes II-IV); arrhythmias of prognostic significance; suspected pulmonary congestion.

Advertencias y precauciones

Consult your doctor or pharmacist before starting to use Ilomedin.

• If you need an urgent amputation (e.g., in the case of infected gangrene), the surgical intervention should not be delayed.

• If you smoke, you should be strongly advised to quit smoking.

• If you have low blood pressure, you should be closely monitored to avoid a further drop in blood pressure, and if you have significant heart disease, you should be closely monitored.

• You should be aware of the possibility of hypotension if you change from a lying down to a standing position after the infusion is completed.

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

Consult your doctor, even if any of the circumstances mentioned above have occurred at any time.

Otros medicamentos e Ilomedin

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Certain medications may interact, in these cases, it may be necessary to change the dose or discontinue treatment with one of the medications. It is especially important to inform your doctor if you are using any of the following medications.

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

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

You should also be aware that in pharmacological studies, iloprost has been shown to have 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 medication contains 4.05 mg of alcohol (ethanol) in each ampule. The amount of this medication is equivalent to less than 1 ml of beer or wine.The small amount of alcohol contained in this medication does not produce any perceptible effect.

Ilomedin contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per ampule; it is essentially "sodium-free".

Embarazo, lactancia y fertilidad

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Ilomedin should not be administered during pregnancy. The potential risk of therapeutic use of iloprost during pregnancy is unknown, so if you are of childbearing age, you should use an effective contraceptive method during treatment.

Ilomedin should not be administered during lactation. It is unknown whether iloprost can pass into breast milk.

Conducción y uso de máquinas

No applicable.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

This medication should only be used in hospitals and properly equipped healthcare centers under strict surveillance.

The perfusion solution must be prepared daily to ensure sterility.

This medication is administered daily for 6 hours as an intravenous perfusion, 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 of body weight/min. The exact perfusion rate must be calculated based on body weight (for more information, see section “6. Additional information of interest to the supervising physician”).

During the first 2 - 3 days, the tolerated dose is established. If side effects such as headache and nausea, or an undesirable decrease in blood pressure appear, the perfusion rate will be reduced to establish the tolerated dose. If severe adverse effects occur, the perfusion must be interrupted. Subsequently, treatment (usually for 4 weeks) should continue with the established tolerated dose during the first 2 - 3 days.

Record blood pressure and heart rate at the beginning of perfusion and after each dose increase.

The treatment duration is up to 4 weeks. In the case of Raynaud's phenomenon (crisis of pallor followed by cyanosis and erythema of the extremities in relation to cold or emotional tension) periods of treatment as short as 3 to 5 days are often sufficient to achieve improvement for several weeks.

Consider if you have renal insufficiency requiring dialysis or liver cirrhosis, as in these situations iloprost elimination decreases and a reduced dose is necessary (e.g., half the recommended dose).

It is not recommended to perform continuous perfusion for several days, given the possibility of an immunization phenomenon on platelet effects or a rebound effect with hyperaggregability of platelets at the end of treatment, although no clinical complications associated with these phenomena have been reported.

Your doctor will indicate the duration of your treatment with Ilomedin. Do not discontinue treatment before.

If you use more Ilomedin than you should

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

In case of presenting symptoms indicating that you have been administered more Ilomedin than necessary, the perfusion of Ilomedin must be interrupted and you must be treated with symptomatic measures. No specific antidote is known.

In the case of overdose or accidental ingestion, consult the Toxicological Information Service; Telephone 91 562 04 20

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

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

The most frequently observed side effects in patients treated with Iloprost (may affect 1 or more than 1 in 10 patients) are headache, flushing (face redness), excessive sweating (hyperhidrosis), and gastrointestinal symptoms such as nausea (urge to vomit) and vomiting.

These are expected to occur at the beginning of treatment while adjusting and establishing the best tolerated dose. However, all these side effects usually disappear quickly with a reduction in dose.

The most serious adverse reactions in which a fatal outcome or life-threatening risk to patients treated with Iloprost have been observed were:

• stroke (cerebrovascular accident)
• myocardial infarction (heart attack)
• pulmonary embolism (difficulty breathing or chest pain when inhaling caused by a blood clot in the lung)
• heart failure (heart insufficiency)
• seizures
• hypotension (abnormally low blood pressure)
• tachycardia (acceleration of heart rhythm)
• asthma
• angina pectoris (chest pain or pressure caused by insufficient blood flow to the heart)
• shortness of breath (dyspnea)
• pulmonary edema (difficulty breathing or coughing up blood caused by fluid accumulation in the lung)

Another group of side effects is related to local reactions at the infusion site. For example, redness and pain at the infusion site or cutaneous vasodilation that causes a linear erythema (redness) over the infusion vein may appear.

The possible side effects are listed below according to their frequency.

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

• headache
• flushing (face redness)
• nausea (urge to vomit)
• vomiting
• excessive sweating (hyperhidrosis)

Common(may affect 1 to 10 patients per 100)

• decreased appetite
• apathy
• confusion
• dizziness / vertigo
• paresthesia (numbness and tingling) / pulsating sensation / hyperesthesia (increased sensation of pain or touch) / burning sensation
• restlessness / agitation
• sedation
• drowsiness
• tachycardia (acceleration of heart rhythm)
• bradycardia (decrease in heart rhythm)
• angina pectoris (chest pain or pressure caused by insufficient blood flow to the heart)
• hypotension (abnormally low blood pressure)
• increased blood pressure
• shortness of breath (dyspnea)
• diarrhea
• abdominal discomfort / abdominal pain
• mandibular pain / trismus (jaw spasms)
• muscle pain / arthralgia (joint pain)
• pain
• fever / increased body temperature
• sensation of heat
• asthenia (weakness) / feeling of discomfort
• chills
• fatigue / tiredness
• thirst
• erythema, pain, and phlebitis at the infusion site (inflammation of the vein)

Uncommon(may affect 1 to 10 patients per 1000)

• thrombocytopenia (blood disorder characterized by ease of 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)
• heart failure (heart insufficiency)
• arrhythmia / extrasystoles (irregular heart rhythm)
• stroke / cerebral ischemia (cerebrovascular accident)
• pulmonary embolism (difficulty breathing or chest pain when inhaling caused by a blood clot in the lung)
• deep vein thrombosis (blood clot formation and displacement into the bloodstream)
• asthma
• pulmonary edema (fluid accumulation in the lungs)
• hemorrhagic diarrhea (diarrhea with blood) rectal bleeding
• indigestion (stomach burning or pain)
• rectal tenesmus (pain due to constipation)
• constipation
• eructation
• difficulty swallowing (dysphagia)
• dry mouth / dysgeusia (alteration of the sense of taste)
• jaundice (yellow discoloration of the skin or white of the eyes and/or itching due to liver alteration)
• pruritus (itching)
• tetany (muscle spasm attack) / muscle spasms
• hypertonia (increase in muscle tension)
• renal pain
• vesical tenesmus (sensation of continuous urge to urinate)
• urinary alterations
• difficulty urinating (dysuria)
• urinary tract alterations

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

• vestibular alteration (dizziness caused by inner ear alteration)
• cough
• proctitis (rectal inflammation)

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 being treated concomitantly with antiplatelet aggregation inhibitors, heparin, or coumarin anticoagulants.

If you experience side effects, consult your doctor or pharmacist, even if they are side effects that do not appear in this prospectus.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Ilomedin

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

Aspect of the product and content of the package

Ilomedin is a clear particle-free solution. A vial contains 0.5ml of solution.

Holder of the marketing authorization:

Bayer Hispania, S.L.

Av. Baix Llobregat 3-5

08970 – Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing:

Berlimed, S.A

Francisco Alonso, s/n. Industrial Park Sta. Rosa.

28806 - Alcalá de Henares

Spain

Date of the last review of thisleaflet: January 2014

Other sources of information

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

This information is intended solely for doctors or healthcare professionals.

Dosage and administration

Ilomedin is administered daily for 6 hours as an intravenous infusion, after dilution, through a central venous catheter or a peripheral vein. During the first 2-3 days, the dose that the patient can tolerate is established. To this end, the treatment must be started at a perfusion rate of 0.5ng/kg/min for 30 minutes. Subsequently, the dose must be increased by 0.5ng/kg/min at approximately 30-minute intervals, until a dose of 2.0ng/kg/min is reached. The exact perfusion rate must be calculated based on body weight to achieve a perfusion rate within the range of 0.5-2.0ng/kg/min (for use with a perfusion pump or injector, see the tables below).

Heart rate and blood pressure must be recorded at the start of the infusion and after each dose increase.

Perfusion rates (ml/h) for different doses for administration via perfusion pump

In general, the ready-to-use solution for perfusion is administered intravenously via a perfusion pump (e.g., Infusomat?). For this purpose, the contents of a 0.5 ml vial of Ilomedin are diluted with 250 ml of sterile physiological saline solution or 5% glucose solution. The contents of the vial and the diluent must be mixed completely. In the case of administering a concentration of Ilomedin of 2?g/ml, the required perfusion rate must be established according to the scheme described previously to achieve a dose within the range of 0.5-2.0ng/kg/min.

(To establish the intermediate perfusion rate and match the patient's body weight with the desired dose in ng/kg/min).

Perfusion rates (ml/h) for different doses for administration via injector

A pump injector with a 50ml syringe (e.g., Perfusor?) can also be used. In this case, the contents of a 0.5ml vial of Ilomedin are diluted with 25ml of sterile physiological saline solution or 5% glucose solution. The contents of the vial and the diluent must be mixed completely. In the case of administering a concentration of Ilomedin of 2?g/ml, the required perfusion rate must be determined according to the scheme described previously to achieve a dose within the range of 0.5-2.0ng/kg/min.

For establishing the intermediate perfusion rate and matching the patient's body weight with the desired dose in ng/kg/min).

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

Pregnancy and lactation

• Pregnancy

Ilomedin must not be administered during pregnancy. There are no sufficient data on 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 medicine must not be mixed or added to any other substance with the ready-to-use solution for perfusion.

Period of validity

4 years.

Instructions for use and handling

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

The ready-to-use solution for perfusion must be prepared daily before administration to ensure its sterility.

• Handling

Oral ingestion and contact with mucous membranes must be avoided.

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