Iloprost 100 micrograms/ml concentrate for solution for infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
• The full name of this medicine is Iloprost 100 micrograms/ml Concentrate for solution for infusion but within the leaflet it will be referred to as Iloprost 100 micrograms/ml.

What is in this leaflet

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

Do not use Iloprost 100 micrograms/ml if you:

• have hypersensitivity (allergy) to iloprost or any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”)
• are at increased risk of bleeding – for example, if you have an active gastric (stomach) or duodenal ulcer, bleeding from wounds or had bleeding inside the skull
• have suspected fluid build-up in the lungs (pulmonary oedema) accompanied by difficulty in breathing
• had a heart attack within the last six months
• have an irregular heart rate
• have poor blood flow to the heart muscle (severe coronary artery disease or unstable angina)
• are suffering with angina or chest pain
• had an acute or chronic congestive heart failure
• have congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension
• had a stroke in the past 3 months
• are pregnant or breast feeding

Warnings and precautions

Talk to your doctor before using Iloprost 100 micrograms/ml if you:

• require urgent amputation. Surgery should not be delayed if you need urgent amputation (e.g. in case of infected gangrene).
• are a smoker. You should stop smoking.
• have liver problems or severe kidney problems, tell your doctor. You may be prescribed a lower dose of Iloprost 100 micrograms/ml and your doctor will monitor you closely.
• have low blood pressure, care should be taken so as not to further reduce blood pressure (hypotension).
• have severe heart disease, you will be monitored closely.

After administration, when moving from a lying to upright position, your blood pressure may fall. This can make you feel dizzy for a while until your blood pressure returns to normal values (this is called "orthostatic hypotension"). Stand up slowly when you get out of bed.

This will help your body get used to this change in position and blood pressure.

If undiluted Iloprost 100 micrograms/ml is infused in the veins this can lead to local changes at the injection site due to extravasation.

If Iloprost 100 micrograms/ml comes into contact with your skin:

Iloprost 100 micrograms/ml solution should not come into contact with your skin or eyes. On contact with the skin, iloprost may cause long-lasting but painless redness of the skin (erythema). In the event of such contact, wash immediately the skin or the eyes with water or saline.

This medicinal product contains small amounts of ethanol (alcohol), less than 100mg per dose.

Other medicines and Iloprost 100 micrograms/ml

Tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Iloprost 100 micrograms/ml and some other medicines may affect each other in the way they work in your body. Take special care to mention any of the following:

• Medicines used to treat high blood pressure or heart disease. Your blood pressure may drop much further. Tell your doctor if you are taking any of these. He/she may change the dose of Iloprost 100 micrograms/ml you should take.
• Medicines that thin the blood or inhibit blood clotting (e.g Aspirin® or acetylsalicylic acid, ticlopidine, clopidogrel). The risk of bleeding may be increased. If you suffer from bleeding, treatment with Iloprost 100 micrograms/ml should be discontinued.

Pregnancy, breast-feeding and fertility:

Iloprost 100 micrograms/ml is not indicated for pregnant or breast-feeding women.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. Women of childbearing potential have to use effective contraception during treatment.

Driving and using machines:

Iloprost 100 micrograms/ml lowers blood pressure and may cause dizziness or light-headedness in some people. Do not drive or operate any tools or machines if you feel these effects.

How Iloprost 100 micrograms/ml is prepared for administration

Iloprost 100 micrograms/ml is a solution contained in a glass ampoule. The content of the ampoule is diluted with 0.9% physiological sodium chloride solution or a 5% glucose solution.

The infusion solution should be prepared just before the infusion daily, to ensure sterility. The content of the ampoule and the diluent must be mixed thoroughly. Iloprost 100 micrograms/ml must be used only after dilution. For further information for physicians or healthcare professionals on the preparation of the dilution see section "The following information is intended for medical and healthcare professionals only" at the end of this leaflet.

How Iloprost 100 micrograms/ml is given

The solution is infused intravenously with a venous catheter directly into one of the veins in your arm or into a central intravenous catheter inserted into a vein near your neck. Iloprost 100 micrograms/ml is administered as infusion over 6 hours daily.

The dose is adjusted according to individual tolerability within the range of 0.5 to 2.0 ng iloprost/kg body weight/min. Your blood pressure and heart rate will be measured at the start of the infusion and after every dose increase.

How much Iloprost 100 micrograms/ml is given

During the first 2-3 days, the individually tolerated dose is established.

For this purpose, your doctor will start the treatment at a low dose. Treatment should be started at an infusion rate of 0.5 ng/kg/min for 30 minutes. The dose should then be increased at intervals of 30 minutes in steps of 0.5 ng/kg/min up to 2.0 ng/kg/min. The exact infusion speed should be calculated on the basis of body weight to reach an infusion within the range of 0.5 to 2.0 ng/kg/min (see tables below for use with infusion pump or syringe driver).

If adverse effects occur, such as headache and nausea or an undesirable drop in blood pressure, tell your doctor immediately. The infusion rate should be reduced until the tolerable dose is found. If the adverse effects are severe, the infusion should be interrupted. For the remaining duration, the treatment should be continued with the dose found to be tolerated in the first 2 to 3 days.

The doctor will determine whether Iloprost 100 micrograms/ml will be infused intravenously by an infusion pump or with syringe driver. If Iloprost 100 micrograms/ml is administered with an infusion pump, it will be diluted before infusion to a final concentration of 0.2 micrograms/ml. If Iloprost 100 micrograms/ml is administered with a syringe driver, it will be diluted before infusion to a final concentration of 2 micrograms /ml.

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

How long Iloprost 100 micrograms/ml is given:

The duration of treatment is up to 4 weeks.

The safety and efficacy of Iloprost 100 micrograms/ml have not been studied for treatment longer than 4 weeks or after repetitive treatment cycles.

Continuous infusion over several days is not recommended, because it can lead to reduced effect on platelets and increased platelet aggregation (platelet hyperaggregability) at the end of treatment. No clinical complications associated with these phenomena have been reported.

If you feel that the effect of Iloprost 100 micrograms/ml is too strong or too weak, tell your doctor or pharmacist.

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

If you use more Iloprost 100 micrograms/ml than you should:

Drop in blood pressure (hypotensive reaction) can be expected, as well as headache, redness of the face (flushing), nausea, vomiting and diarrhoea. An increase in blood pressure, reduced or increased heart rate and limb or back pain may also occur.

No specific antidote is known.

In case of overdose, your doctor is advised to discontinue infusion of iloprost, to monitor you and treat your symptoms.

If you stop using Iloprost 100 micrograms/ml:

If the infusion therapy with Iloprost 100 micrograms/ml is discontinued, your doctor will take care to restore the changes that might have been made to other medicines you take, due to Iloprost 100 micrograms/ml administration (e.g. dose reductions).

Possible side effects are listed below according to their frequency:

Common (may affect up to 1 in 10 people)

• Decreased appetite
• Apathy
• Confusional state
• Dizziness/vertigo (feeling of ‘spinning’)
• Paraesthesia (numbness and tingling)/palpitations/hyperesthesia (increased sensitivity to pain or touch)
• Agitation
• Drowsiness
• Tachycardia (fast heart rate)
• Bradycardia (slow heart rate)
• Angina pectoris (chest pain or discomfort due to insufficient blood flow to the heart)
• Hypotension (abnormally low blood pressure)
• Blood pressure increased
• Dyspnoea (difficulty breathing)
• Diarrhoea
• Abdominal discomfort/abdominal pain
• Pain in jaw/trismus (jaw spasm, locking jaw)
• Myalgia (muscle pain)/arthralgia (joint pain)
• Pain
• Fever/body temperature increased
• Burning sensation
• Asthenia (weakness)/malaise (feeling of major weakness)
• Chills
• Fatigue
• Thirst
• Infusion site reactions such as infusion site erythema, infusion site pain or infusion site phlebitis (vein irritation)

Uncommon (may affect up to 1 in 100 people)

• Thrombocytopenia (blood disorder characterized by easy bruising or bleeding)
• Hypersensitivity (allergy)
• Anxiety, depression, hallucination
• Syncope (short loss of consciousness)
• Tremor (trembling or shaking)
• Migraine
• Blurred vision
• Eye irritation
• Eye pain
• Arrhythmia/extrasystoles (abnormal heart rate)
• Deep vein thrombosis (pain in the legs due to a blood clot in the blood vessels of the legs)
• Haemorrhagic diarrhoea (diarrhoea with blood in stools)
• Rectal haemorrhage
• Dyspepsia (heartburn or stomach pain)
• Rectal tenesmus (pain due to constipation)
• Constipation
• Dysphagia (difficulty swallowing)
• Dry mouth
• Dyspepsia (sense of taste disorder)
• Liver disorder (hepatic impairment)
• Jaundice (yellowing of the skin and white of the eye and/or itching due to hepatic disorder)
• Pruritus (itching)
• Tetany (prolonged painful muscle spasm), muscle spasms
• Hypertonia (increased muscle tension)
• Kidney pain
• Vesical tenesmus (failed urinary urgency)
• Abnormal urine
• Dysuria (painful urination or difficulty urinating)

Rare (may affect up to 1 in 10,000 people)

• Cough
• Proctitis (rectal irritation)

Iloprost may cause chest pain or discomfort due to angina pectoris, especially in patients with coronary artery disease.

The risk of bleeding is increased in patients when inhibitors of platelet aggregation, heparin or anticoagulants of the coumarin-type are given concomitantly.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

What Iloprost 100 micrograms/ml contains:

• The active substance is iloprost
  1 ml of Iloprost 100 micrograms/ml contains 100 micrograms of iloprost (equivalent to 134 micrograms iloprost trometamol).
• The other ingredients are: trometamol, ethanol 96% (v/v), sodium chloride, hydrochloric acid for pH adjustment and water for injection.

What Iloprost 100 micrograms/ml looks like and contents of the pack

• Iloprost 100 micrograms/ml is a clear colourless solution, free of visible particles which is diluted prior to infusion via a vein. It is supplied in glass ampoules.
• Iloprost 100 micrograms/ml is available in the following pack sizes:

1 Box of 1 or 5 ampoules, each with 0.5 ml concentrate for solution for infusion or 1 box of 1 or 5 ampoules, each with 1 ml concentrate for solution for infusion.

Not all pack sizes may be marketed.

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