ILOPROST

Iloprost concentrate for solution for infusion is NOT ready to use and requires dilution before administration. Iloprost concentrate for solution for infusion should be administered under strict monitoring in a hospital or out-patient clinic setting with adequate facilities.

Pregnancy should be excluded before the start of treatment in women. 6 as an intravenous infusion over 6 hours via a peripheral vein or a central venous catheter. 0 nanograms iloprost /kg body weight/min. The infusion solution should be made up just before the infusion to ensure sterility.

Iloprost concentrate for solution for infusion should only be used diluted. To avoid incompatibility, no other products should be added to the infusion prepared for injection. The content of the ampoule and the diluent must be mixed thoroughly.

Posology Blood pressure and heart rate should be monitored at the start of the infusion and subsequently at every dose increase. During the first 2-3 days, the individually tolerated dose is established. 5 nanograms /kg/min for 30 minutes.

0 nanograms /kg/min. 0 nanograms /kg/min (see tables below for use with infusion pump or syringe driver). Method of administration Iloprost concentrate for solution for infusion is NOT ready to use and requires dilution before administration.

Depending on the occurrence of adverse effects such as headache and nausea or an undesired blood pressure drop, the infusion rate should be reduced until the optimal tolerated dose is found. If the adverse effects are severe, the infusion should be temporarily interrupted.

The treatment course can then be continued with the dose based on the optimal tolerated dose reached in the first 2 to 3 days of treatment. Depending on the infusion technique used, there are two different methods to dilute the content of the ampoule.

g. Infusomat®). A more concentrated solution may be administered via a syringe driver. 6. Infusion rates (ml/hour) for different doses using an automatic infusion pump. 6). 0 nanograms /kg/min. The following table (Table 1) can be used to calculate the infusion rate corresponding to the individual weight of the patient and the dose to be administered.

Match the 3 patient's actual body weight on the table, then set the infusion rate on the pump, based on the desired dose in nanograms/kg/min. g. Perfusor®) may also be used to infuse iloprost. 6. 0 nanograms/kg/min. The following table (Table 2) can be used to calculate the infusion rate corresponding to the individual weight of the patient and the dose to be infused.

Summary of safety profile The overall safety profile of iloprost is based on data from post-marketing surveillance as well as on pooled clinical trial data. The raw incidence was based on the cumulative database of 3,325 patients having received iloprost either in controlled or uncontrolled clinical trials or in a compassionate use program from generally elderly and multimorbid patients with peripheral arterial occlusive disease (PAOD) in advanced stages III and IV, and patients with thromboangitis obliterans (TAO); for details see Table 1.

The most common observed adverse events (≥ 10%) in patients receiving iloprost in clinical trials are headache, flushing, nausea, vomiting and hyperhidrosis. These undesirable effects are likely to occur during the dose titration at the start of treatment to identify the best tolerable dose for the individual patient.

Usually, these undesirable effects resolve with dose reduction. Overall, the most severe undesirable effects (life-threatening or fatal) in patients receiving iloprost are cerebrovascular stroke, myocardial infarction, pulmonary embolism, cardiac failure, convulsion, hypotension, tachycardia, asthma, angina pectoris, dyspnoea, and pulmonary oedema.

Another group of side effects is related to the local infusion site reactions. For example, infusion site redness and infusion site pain may occur or a cutaneous vasodilation may give rise to a linear erythema above the infusion vein.

Tabulated list of adverse reactions The table below shows the frequencies of adverse reactions which have been reported in clinical studies and post-marketing experience. known (frequency cannot be estimated from available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥1/10,000 to <1/1,000) Blood and lymphatic disorders Thrombocytopenia Immune system disorders Hypersensitivity Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Bradypsychia Confusional state Anxiety Depression Hallucination 8 Nervous system disorders Headache Dizziness/Vertigo Paraesthesia/ Palpitations/ Hyperaesthesia/ Burning sensation, Nervousness/Restle ssness/ drowsiness Convulsion* Syncope Tremor Migraine Eye disorders Vision blurred Eye irritation Eye pain Cardiac disorders Tachycardia* Bradycardia Angina pectoris* Myocardial infarction* Cardiac failure* Arrhythmia/ Extrasystoles* Vascular disorders Flushing Hypotension* Blood pressure increased Cerebrovascular event*/ Cerebral ischaemia Pulmonary embolism* Deep vein thrombosis Respiratory, thoracic and mediastinal disorders Dyspnoea* Asthma* Pulmonary oedema* Cough Gastrointestinal disorders Nausea Vomiting Diarrhoea Abdominal discomfort/ Abdominal pain Diarrhoea Haemorrhagic Rectal haemorrhage Dyspepsia Rectal tenesmus Constipation Dysphagia Dry mouth/Dysgeusia Proctitis Hepatobiliary disorders Hepatic impairment Skin and subcutaneous disorders Hyperhidrosis Pruritus Musculoskeletal Pain in Tetany/Muscle System organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥1/10,000 to <1/1,000) and connective jaw/Trismus spasms 9 tissue disorders Myalgia/Arthralgia Renal and urinary disorders Kidney pain Dysuria General disorders and administration site conditions Pain, Pyrexia/Body temperature increased, Feeling hot, Asthenia, Chills, generalised warmth, Thirst Infusion site reactions (infusion site erythema, infusion site pain, infusion site phlebitis) Injury, poisoning and procedural complications *life-threatening and/or fatal cases have been reported Iloprost may cause angina pectoris, especially in patients with coronary artery disease.

g. in cases of infected gangrene). Patients who are smokers should be strongly advised to stop smoking. 2). 2) and close clinical monitoring are required. In patients with low blood pressure care should be taken to avoid further hypotension.

Also, patients with significant heart disease should be closely monitored. The possibility of orthostatic hypotension should be considered in patients getting up from the lying to an upright position after the end of administration.

3 risk of haemorrhage, intracranial haemorrhage). Special precautions Accidental infusion of undiluted iloprost may result in local changes at the injection site. Therefore, a dedicated intravenous cannula should be placed for the infusion of iloprost and the patency of the line should be checked during infusion.

Oral ingestion and contact with the mucous membranes should be avoided. On contact with the skin, iloprost may cause long-lasting but painless erythema. Suitable precautions should therefore be taken to avoid iloprost contact with the skin.

In the event of such contact, the affected area should be washed immediately with copious amounts of water or saline. 5 ml vial of concentrate respectively. The amount in 1 ml of this medicinal product is equivalent to less than 1 ml beer or wine.

The small amount of alcohol in this medicinal product will not have any noticeable effects. 08 mg sodium in 1 ml of the concentrate, that is to say essentially “sodium-free”. 6

1. g. active peptic ulcer, trauma, intracranial haemorrhage). g. transient ischemic attack, stroke) within the last 3 months • Pulmonary oedema • Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.