Iloprost Zentiva 100 micrograms/ml concentrate for solution for infusion

• 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. See section 4.

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

• are allergic to iloprost or any of the other ingredients of this medicine (listed in section 6).
• are at increased risk of bleeding - for example if you have a 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 (arrhythmias).
• 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 clinical relevant myocardial function disorders not related to pulmonary hypotension.
• had a stroke in the past three months.
• are pregnant or breast-feeding (see ‘Pregnancy, breast-feeding and fertility’).

If you think that any of the above applies to you, talk to your doctor.

Talk to your doctor before Iloprost is given to you 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 and your doctor will monitor 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 is infused in the veins, this may lead to local changes at the injection site due to extravasation.

If Iloprost comes into contact with your skin or eyes:

This medicine 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.

The safety and efficacy of iloprost in children aged up to 18 years have not been established.

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Iloprost and some other medicines may affect each other in the way they work in your body. Tell your doctor if you are taking:

• 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 you are given.
• 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 bleeding, treatment with Iloprost should be discontinued.

Iloprost is not indicated for pregnant or breastfeeding 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 this medicine is given to you.

This medicine must not be used during pregnancy or while breast-feeding.

Women of childbearing potential have to use effective contraception during treatment.

Iloprost 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.

Important information about some of the ingredients of Iloprost Ethanol This medicine contains 8.10 mg of alcohol (ethanol) in each ml of the concentrate. The small amount of alcohol in this medicine will not have any noticeable effects.

This medicine contains 7.08 mg sodium in 1 ml of the concentrate, that is to say essentially “sodium-free”.

Iloprost concentrate for solution for infusion is NOT ready to use and requires dilution before administration.

Iloprost is a solution contained in a glass ampoule. The content of the ampoule is diluted with physiological saline solution or a 5% glucose solution. The infusion should be prepared just before it is administered to ensure sterility.

The content of the ampoule and the diluent must be mixed thoroughly.

Iloprost 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.

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 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 nanograms iloprost/kg body weight/min. iloprost/kg/min.

Your blood pressure and heart rate will be measured at the start of the infusion and after every dose increase.

During the first 2 to 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 nanograms/kg/min for 30 minutes. The dose should then be increased at intervals of 30 minutes in steps of 0.5 nanograms/kg/min up to a maximum of 2.0 nanograms/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 nanograms/kg/min.

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 will be infused intravenously by an infusion pump or with an injector. If Iloprost is administered with an infusion pump, it will be diluted before infusion to a final concentration of 0.2 micrograms/ml.

If Iloprost is administered with an injector, it will be diluted before infusion to a final concentration of 2 micrograms/ml.

If you have kidney problems 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.

The duration of the treatment is up to 4 weeks.

The safety and efficacy of Iloprost has not been studied for treatment for longer than 4 weeks or after repetitive 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 is too strong or too weak, tell your doctor.

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

Common (may affect up to 1 in 10 people):

• Decreased appetite.
• Apathy
• Confused state
• Dizziness/vertigo (feeling of spinning)
• Paraesthesia (numbness and tingling)/ palpitations/ hyperaesthesia (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 pain/ 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
• Thirst
• Infusion site reactions such as infusion of 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, hallucinations
• 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 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 difficult urinating)

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

• Cough
• Proctitis (rectal irritation)

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

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

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 the Yellow Card Scheme at: 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.

• The active substance is iloprost. Each ampoule contains 0.5 ml concentrate for solution for infusion containing 50 micrograms Iloprost (as Iloprost trometamol). Each 1 ml of concentrate for solution for infusion contains 100 micrograms Iloprost (as Iloprost trometamol).
• The other ingredients are, trometamol, ethanol 96%, sodium chloride, hydrochloric acid dilute (as pH adjusting agent), water for injection.

Clear and colourless solution free of visible particles.

Clear Type I glass 1 ml ampoule, in a PVC blister and paper folding carton.

Pack sizes: 1 ampoule and 5 ampoules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Manufacturer