PACKAGE LEAFLET: constriction of the muscles in the walls of INFORMATION FOR THE USER the small airways) and wheezing. Tell your doctor if you have a lung infection, severe Iloprost 10 microgram/ml , or chronic lung disease (chronic obstructive pulmonary disease). Your doctor nebuliser solution will monitor you closely. iloprost • Your blood pressure will be checked before treatment and if it is too low (less Read all of this leafl et carefully before you than 85 mmHg for the upper value) then start using this medicine because it contains therapy with iloprost should not be started. important information for you. • In general, you will need to take special − Keep this leafl et. You may need to read it care to try and avoid eff ects of low blood again. pressure, such as fainting and dizziness: − If you have any further questions, ask your • Tell your doctor if you are taking any doctor, pharmacist or nurse. other because the combined − This medicine has been prescribed for you eff ect with iloprost may lower your only. Do not pass it on to others. It may harm blood pressure further (see below “Other them, even if their signs of illness are the medicines and iloprost”). same as yours. • Stand up slowly when you get out of − If you get any side eff ects, talk to your doctor, chairs or bed. pharmacist or nurse. This includes any • If you tend to faint as soon as you get out possible side eff ects not listed in this leafl et of bed, it may be helpful to take your fi rst (see section 4). dose of the day while you are still lying down. What is in this leafl et • If you tend to experience fainting 1. What iloprost is and what it is used for episodes, avoid any exceptional straining, 2. What you need to know before you use for example during physical exertion; it iloprost might be useful to inhale iloprost before. 3. How to use iloprost Fainting episodes may be due to the 4. Possible side eff ects underlying disease. Tell your doctor if they 5. How to store iloprost get worse. He/she may consider adjusting 6. Contents of the pack and other information your dose or changing your treatment. • If you suff er from a weak heart condition 1. What iloprost is and what it is used for such as right , and feel that your disease is worsening, tell your doctor. What iloprost is Symptoms can include swelling of feet and The active substance of Iloprost 10 microgram/ ankles, , palpitations, ml nebuliser solution is iloprost. It imitates urinating more frequently at night or a natural substance in the body called oedema. Your doctor will consider changing . Iloprost inhibits unwanted your treatment. blocking or narrowing of blood vessels and • If you experience diffi culty breathing, allows more blood to fl ow through the vessels. cough up blood, and/or sweat excessively these may be signs that you have water in What iloprost is used for the lungs (lung oedema). Stop using iloprost Iloprost is used to treat moderate cases of and tell your doctor immediately. He/she primary (PPH) in will look for the cause and take appropriate adult patients. PPH is a category of pulmonary measures. hypertension where the cause of the high • If you have liver problems or very severe blood pressure is not known. kidney problems, requiring dialysis, This is a condition where blood pressure is too tell your doctor. You may be gradually high in the blood vessels between the heart introduced to the prescribed dose or be and the lungs. prescribed a lower dose of iloprost than for Iloprost is used to improve exercise capacity other patients (see section 3. “How to use (the ability to carry out physical activity) and iloprost”). symptoms. Contact of iloprost with skin or swallowing How iloprost works iloprost Breathing in the mist carries iloprost to the • Do NOT let iloprost solution come into lungs, where it can work most eff ectively in contact with your skin or eyes. If it does, rinse the artery between heart and lungs. Improved the skin or your eyes immediately with plenty blood fl ow leads to a better supply of oxygen to of water. the body and reduced strain on the heart. • Do NOT drink or swallow iloprost solution. If you swallow it accidentally, drink plenty of 2. What you need to know before you use water and tell your doctor. iloprost Children and adolescents Do not use iloprost The safety and effi cacy of iloprost in children • if you are allergic to iloprost or any of the aged up to 18 years have not been established. other ingredients of this medicine (listed in section 6). Other medicines and iloprost • if you are at risk of bleeding – for example, Tell your doctor or pharmacist if you are if you have an active ulcer of the stomach using, have recently used or might use any or of the fi rst part of the small intestine other medicines. Iloprost and certain other (duodenal ulcers), if you have suff ered medicines may aff ect each other in the way a physical injury (trauma), if you are at risk of they work in your body. Tell your doctor if you bleeding within the skull. are taking: • if you have a heart problem, such as: • Medicines used to treat high blood - poor blood fl ow to the heart muscles pressure or heart disease, such as (severe coronary heart disease or unstable - beta blockers, angina). Symptoms can include chest pain. - nitro-vasodilators, - a heart attack within the last six months. - ACE inhibitors. - a weak heart (decompensated cardiac Your blood pressure may drop much further. failure) which is not under close medical Your doctor may change the dosage. observation. - severe unstable heartbeat . • Medicines that thin the blood or inhibit - a defect of the heart valves (inborn blood clotting, this includes or acquired) that causes the heart to - acetylsalicylic acid (ASA - a compound found work poorly (not related to pulmonary in many medicines that lower and hypertension). relieve pain), • if you have had a stroke within the last - , 3 months, or any other occurrence that - -type , such as reduced the blood supply to the brain (e.g. or , transient ischaemic attack). - non-steroidal anti-infl ammatory drugs, • if your pulmonary hypertension is due - non-selective phosphodiesterase inhibitors to a blocked or narrowed vein (venous such as pentoxifylline, occlusive disease). - selective phosphodiesterase 3 (PDE 3) inhibitors, such as or anagrelide, Warnings and precautions - , Talk to your doctor, pharmacist or nurse before - , using iloprost: - glycoprotein IIb/IIIa antagonists, such as • Inhaling iloprost might trigger breathing o , diffi culties (see section 4), especially in o eptifi batide, patients with bronchospasm (sudden o tirofi ban, -1-

- defi brotide. • Breelib nebuliser Your doctor will monitor you carefully. If you are starting iloprost treatment or if you Before taking any medicine ask your doctor switch from an alternative device your fi rst or pharmacist, who has more information on inhalation will be with Iloprost 10 microgram/ medicines to be careful with or avoid when ml. If you tolerate this dose well, your next dose using iloprost. should be increased using another available presentation on the market containing Iloprost with food and drink 20 microgram/ml of iloprost. You should Food or drink is not expected to aff ect iloprost. continue on this dose. However, you should avoid taking food or drink during inhalation. If you cannot tolerate inhalation of this higher dose talk to your doctor who may decide that Pregnancy you should take Iloprost 10 microgram/ml. • If you suff er from pulmonary hypertension, avoid getting pregnant as Most people will have 6 to 9 inhalation pregnancy may lead to a worsening of your sessions spread throughout the day. One condition and may even endanger your life. inhalation session with Breelib will usually last • If you could get pregnant, use reliable about 3 minutes. contraception from the time you start treatment and during treatment. Your doctor will supervise your treatment • If you are pregnant, think you may be when you start using the Breelib nebuliser to pregnant or are planning to have a baby, ensure that you tolerate the dose and speed of tell your doctor straight away. Iloprost should inhalation well. only be used during pregnancy if your doctor decides that the potential benefi t outweighs • I-Neb AAD nebuliser the potential risk to you and the foetus. In general, when starting iloprost treatment Breast-feeding the fi rst inhaled dose should be 2.5 microgram It is not known whether iloprost passes into iloprost as delivered at the mouthpiece. If you human milk. A potential risk to the breast- tolerate this dose well, your dose should be feeding child cannot be excluded and it is increased to 5 microgram iloprost and you preferable to avoid breast-feeding during should continue on this dose. If you are unable iloprost therapy. to tolerate the 5 microgram dose, the dose should be reduced to 2.5 microgram. Ask your doctor or pharmacist for advice before taking any medicine. Most people will have 6 to 9 inhalation sessions spread throughout the day. One inhalation Newborns, infants and pregnant women session will usually last about 4 to 10 minutes should not be in the same room while you with I-Neb AAD depending on the prescribed are inhaling iloprost. dose. Driving and using machines • Venta-Neb nebuliser (2 ampoules of Iloprost lowers blood pressure and may cause iloprost) dizziness or light-headedness in some people. Do not drive or operate any tools or machines if In general, when starting iloprost treatment you feel these eff ects. the fi rst inhaled dose should be 2.5 microgram iloprost as delivered at the mouthpiece. If Iloprost contains ethanol you tolerate this dose well, your dose should Iloprost contains small amounts of ethanol be increased to 5 microgram and you should (alcohol), less than 100 mg per dose. continue on this dose. If you are unable to tolerate the 5 microgram dose, the dose should 3. How to use iloprost be reduced to 2.5 microgram. Iloprost therapy should only be initiated Most people will have 6 to 9 inhalation by a physician experienced in treatment of sessions spread throughout the day. One pulmonary hypertension. inhalation session with Venta-Neb will usually last about 4 to 10 minutes depending on the How much to inhale and for how long prescribed dose. Always use this medicine exactly as your doctor has told you. Check with your doctor if you are Depending on your individual needs, iloprost not sure. can be used for long term treatment. The dose of iloprost and the duration of If you have kidney or liver problems treatment that is right for you depend on your individual condition. Your doctor will advise There is no need to alter the dose in patients you. Do not change the recommended dose with mild or moderate kidney problems without consulting your doctor fi rst. (patients with a creatinine clearance >30 ml/ min). Diff erent nebuliser devices can be used to If you have very severe kidney problems and administer iloprost. Depending on the type of require dialysis or if you have liver problems, device used and dose prescribed, 1 ml or 2 ml of your doctor will introduce you to iloprost iloprost are appropriate. gradually and possibly prescribe fewer daily inhalations. Start therapy by inhaling -2- The following information is intended for • I-Neb AAD healthcare professionals only: The I-Neb AAD System is a portable, hand-held, vibrating mesh technology nebuliser system. This Instructions for use and handling system generates droplets by ultrasound, which Patients stabilised on one nebuliser should forces the solution through a mesh. The I-Neb not switch to another nebuliser without close AAD nebuliser has also been shown to be suitable supervision by the treating doctor as diff erent for the administration of iloprost 10 mcg/ml. The nebulisers have been shown to produce aerosols measured MMAD of the aerosol droplets was 2.1 with slightly diff erent physical characteristics micrometres. and may have faster delivery of the solution (see section 5.2 of the Summary of Product This nebuliser monitors the breathing pattern Characteristics). to determine the aerosol pulse time required to To minimise accidental exposure, it is deliver the pre-set dose of 2.5 or 5 microgram recommended to keep the room well ventilated. iloprost. The dose delivered by the I-Neb AAD system • Breelib is controlled by the medication chamber in When using the Breelib nebuliser please follow the combination with a control disc. Each medication instructions for use provided with the device. chamber is colour coded and has a corresponding Fill the medication chamber with Iloprost colour coded control disc: immediately before use. • For the 2.5 microgram dose the medication Dose of chamber with the red latch is used together Drug Iloprost Estimated with the red control disc. Device product at mouth- inhalation time piece • For the 5 microgram dose the medication Iloprost chamber with the purple coloured latch is Breelib 10 mcg/ml 2.5 mcg 3 minutes used together with the purple control disc. 2.5 microgram iloprost using 1 ml ampoule of The table below provides a summary of the iloprost. Use dosing intervals of 3 – 4 hours (this user instructions of the I-Neb: corresponds to a maximum of 6 administrations Drug Dos- I-Neb AAD per day). Thereafter, your doctor may cautiously products age shorten the dosing intervals depending on Medication Control how you tolerate the treatment. If your doctor chamber disc decides to further increase the dose up to latch 5 microgram, again dosing intervals of 3 - 4 Iloprost 2.5 red red hours should be chosen initially and shortened 10 mcg/ml mcg depending on how you tolerate the treatment. 5 mcg purple purple If you feel that the eff ect of iloprost is too • Venta-Neb strong or too weak, talk to your doctor or 1. Just before you start to inhale, break the pharmacist. glass of 2 ampoules containing 1 ml solution Ask your doctor to have someone help you and pour the complete contents into the become thoroughly familiar with the use nebuliser medication chamber. of the nebuliser. You should not switch to 2. Two programmes can be operated another nebuliser without consulting the 3. Your doctor will adjust Venta-Neb to the doctor who is treating you. programme you need to receive the dose prescribed for you. How to inhale • P1 Programme 1: 5 microgram active substance on the mouth piece 25 For each inhalation session you should use inhalation cycles. a new ampoule of iloprost. Just before you start • P2 Programme 2: 2.5 microgram active to inhale, break the glass ampoule and pour the substance on the mouth piece 10 solution into the medication chamber following inhalation cycles. the instructions for use of the nebuliser. 4. You should use the green baffl e plate to obtain the optimal droplet size for the Follow carefully the instructions that come with administration of iloprost. the nebuliser especially the instructions on Device Dose of iloprost Estimated hygiene and cleaning of the nebuliser. at mouthpiece inhalation time Always take iloprost exactly as your doctor has Venta- 2.5 microgram 4 min told you. Neb 5 microgram 8 min - Iloprost nebuliser solution is inhaled using For further details please refer to the instruction the nebulisers your doctor prescribed (either manual of the nebuliser device or ask your the Breelib, the Venta-Neb or the I-Neb AAD doctor. system). - The nebuliser turns iloprost solution into If you use more iloprost than you should a mist which you breathe in through your Using more iloprost than you should may lead mouth. to dizziness, headache, fl ushing (reddening - For the inhalation you should use of the face), nausea (feeling sick), jaw pain or a mouthpiece to prevent iloprost coming back pain. You may also experience a decrease into contact with your skin. Do not use or an increase in blood pressure, bradycardia a facial mask. (reduced heart rate), tachycardia (increased - Follow carefully any instructions that come heart rate), vomiting, diarrhoea or limb pain. If with the nebuliser. Check with your doctor or any of these happen when you have used more pharmacist if you are unsure. iloprost than you should: - Any iloprost solution remaining in the • stop the inhalation session nebuliser after inhalation must be thrown • talk to your doctor away (see section 5). Your doctor will monitor you and treat any resulting symptoms. A specifi c antidote is not Room ventilation known. Be sure to ventilate or air the room in which you have taken your iloprost treatment. Other If you forget to use iloprost people might accidentally be exposed to Do not take a double dose to make up for iloprost through the room air. In particular, a forgotten dose. Please ask your doctor what newborns, infants and pregnant women should you should do. not be in the same room while you are inhaling iloprost. If you stop using iloprost If you stop or wish to stop treatment, discuss it • Breelib with your doctor fi rst. Fill the medication chamber with Iloprost immediately before use. For fi lling please follow If you have any further questions on the use of the instructions for use of the nebuliser. this medicine, ask your doctor, pharmacist or Dose of Estimated nurse. Device Drug Iloprost at inhalation product mouthpiece time 4. Possible side eff ects Iloprost Breelib 10 mcg/ml 2.5 mcg 3 minutes Like all medicines, this medicine can cause side eff ects, although not everybody gets them. • I-Neb AAD The following serious side eff ects may occur. In 1. Just before you start to inhale, break the this case talk to your doctor immediately. glass ampoule containing 1 ml solution and pour the complete contents into the Very common (may aff ect more than 1 in 10 nebuliser medication chamber. people): 2. The pre-set dose provided by the I-Neb • Bleeding events (mostly nosebleed (epistaxis) AAD system is controlled by the medication and coughing up blood (haemoptysis)) chamber in combination with a control may very commonly occur, especially if you disc. There are two diff erent colour coded are also taking blood-thinning medicines medication chambers. For each medication (anticoagulants). The risk of bleeding may chamber there is a corresponding colour be increased in patients when inhibitors of coded control disc: aggregation or anticoagulants are - For the 2.5 microgram dose the medication given at the same time (see also section 2). chamber with the red coloured latch is Very rarely, fatal cases including bleeding used together with the red control disc. in the brain (cerebral and intracranial - For the 5 microgram dose the medication haemorrhage) have been reported. chamber with the purple coloured latch is used together with the purple control disc. Common (may aff ect up to 1 in 10 people): 3. In order to ensure that you receive the • Fainting () is a symptom of the illness prescribed dose, check the colour of the itself but can also occur during treatment medication chamber and the colour of the with iloprost (see also section 2 “Warnings control disc. and precautions”, for advice on what you can They should both have the same colour, either do to avoid this). red for the 2.5 microgram dose or purple for the • Low blood pressure () 5 microgram dose. Device Dose of iloprost Estimated Not known (frequency cannot be estimated at mouthpiece inhalation time from the available data): • Bronchospasm (sudden constriction of the I-Neb AAD 2.5 microgram 3.2 min muscles in the walls of the small airways) and 5 microgram 6.5 min wheezing (see also section 2 “Warnings and precautions”). -3-

wastewater or household waste. Ask your Below we list other possible side eff ects by how pharmacist how to throw away medicines you likely they are: no longer use. These measures will help protect the environment. Very common (may aff ect more than 1 in 10 people): 6. Contents of the pack and other • widening of the blood vessels information (vasodilatation). Symptoms can be fl ushing or reddening of the face. What iloprost contains • chest discomfort / chest pain • coughing • The active substance is iloprost. • headache Each ampoule with 1 ml contains • nausea 10 microgram iloprost (as iloprost • pain in jaw/spasm of the jaw muscles trometamol). (trismus) • swelling of the limbs (peripheral oedema) • The other ingredients are trometamol, ethanol 96%, sodium chloride, hydrochloric Common (may aff ect up to 1 in 10 people): acid dilute for pH adjustment, and water for • breathing diffi culties (dyspnoea) injection. • dizziness • vomiting Iloprost is provided in clear glass ampoules • diarrhoea (hydrolytic class No. I), containing 1.0 ml of • pain when swallowing (pharyngolaryngeal solution, packed in blisters and paper boxes. irritation) • throat irritation What iloprost looks like and contents of the • mouth and tongue irritation including pain pack • rash • fast heartbeat (tachycardia) Iloprost is a clear and colourless solution free of • awareness of fast or hard heartbeat visible particles for inhalation with the Breelib, (palpitations) the I-Neb or the Venta-Neb nebuliser. Not known (frequency cannot be estimated Iloprost is available in packs containing: from the available data): 10 x 1 ml (2 blisters with 5 ampoules) • reduction in the number of blood 30 x 1 ml (6 blisters with 5 ampoules) (thrombocytopenia) 40 x 1 ml (8 blisters with 5 ampoules) • hypersensitivity (i.e. allergy) 42 x 1 ml (8 blisters with 5 ampoules and 1 • disturbed sense of taste (dysgeusia) blister with 2 ampoules) 168 x 1 ml (33 blisters with 5 ampoules and 1 Other possible eff ects blister with 3 ampoules) • Swelling, mainly of the ankles and legs, due Multipacks containing 160 ampoules (4 inner to fl uid retention (peripheral oedema) is boxes containing 8 blisters with 5 ampoules) a very common symptom of the illness itself Not all pack sizes may be marketed. but can also occur during treatment with iloprost. Marketing Authorisation Holder Zentiva Pharma UK Limited Reporting of side eff ects 12 New Fetter Lane If you get any side eff ects, talk to your doctor London or pharmacist. This includes any possible side EC4A 1JP eff ects not listed in this leafl et. You can also United Kingdom report side eff ects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or Manufacturer search for MHRA Yellow Card in the Google Play Zentiva, k.s., U kabelovny 130, Dolní Měcholupy, or Apple App Store. 102 37, Prague 10, Czech Republic By reporting side eff ects you can help provide more information on the safety of this This leafl et was last revised in May 2020 medicine. 5. How to store iloprost Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and on the carton after EXP. The expiry date refers to the last day of that month. This medicine does not require any special storage conditions. Do not freeze. Any iloprost solution remaining in the nebuliser after inhalation must be thrown away. Do not throw away any medicines via ZV/640 85 -4- For each inhalation session with the I-Neb AAD, transferred into the nebuliser medication chamber the content of one 1 ml ampoule of iloprost immediately before use. is transferred into the medication chamber Two programmes can be operated: immediately before use. • P1 Programme 1: 5 microgram active substance Device Dose of iloprost at Estimated on the mouth piece 25 inhalation cycles. mouthpiece inhalation • P2 Programme 2: 2.5 microgram active time substance on the mouth piece 10 inhalation I-Neb AAD 2.5 microgram 3.2 min cycles. 5 microgram 6.5 min The selection of the pre-set programme is made by the doctor. The table below provides a summary of the user instructions of the I-Neb for iloprost: Venta-Neb prompts the patient to inhale by an Drug prod- Dosage I-Neb AAD optical and an acoustic signal. It stops after the uct pre-set dose has been administered. To obtain Medication Control disc the optimal droplet size for the administration of chamber latch iloprost the green baffl e plate should be used. For Iloprost 2.5 mi- red red details refer to the instruction manual of the Venta- 10 mcg/ml crogram Neb nebuliser. 5 micro- purple purple gram Device Dose of iloprost at Estimated mouthpiece inhalation time • Venta-Neb Venta-Neb 2.5 microgram 4 min Venta-Neb, a portable ultrasonic battery-powered 5 microgram 8 min nebuliser, has also been shown to be suitable for the administration of iloprost 10 mcg/ml. The The effi cacy and tolerability of inhaled iloprost measured MMAD of the aerosol droplets was when administered with other nebulising systems, 2.6 micrometres. For each inhalation session, which provide diff erent nebulisation characteristics the content of two ampoules containing 1 ml of iloprost solution, have not been established. of iloprost 10 mcg/ml. nebuliser solution is ZV/640 85