ILOPROST 20 MCG/ML NEBULISER SOLUTION - patient leaflet, side effects, dosage

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1. What Iloprost is and what it is used for

What Iloprost is used for

Iloprost is used to treat moderate cases of primary pulmonary hypertension (PPH) in adult patients. PPH is a category of pulmonary hypertension where the cause of the high blood pressure is not known. This is a condition where blood pressure is too high in the blood vessels between the heart and the lungs.

Iloprost is used to improve exercise capacity (the ability to carry out physical activity) and symptoms.

How Iloprost works

Breathing in the mist carries Iloprost to the lungs, where it can work most effectively in the artery between heart and lungs. Improved blood flow leads to a better supply of oxygen to the body and reduced strain on the heart.

2. What you need to know before you use Iloprost

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- if you have liver problems or very severe kidney problems, requiring dialysis, tell your doctor. you may be gradually introduced to the prescribed dose or be prescribed a lower dose of iloprost than for other patients (see section 3. “how to use iloprost”).

Contact of Iloprost with skin or swallowing Iloprost

• – Do NOT let Iloprost solution come into contact with your skin or eyes. If it does, rinse the skin or your eyes immediately with plenty of water.

• – Do NOT drink or swallow Iloprost solution. If you swallow it accidentally, drink plenty of water and tell your doctor.

Children and adolescents

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

Other medicines and Iloprost Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Iloprost and certain 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, such as: – Beta blockers.

• – Nitro-vasodilators.

• – ACE inhibitors.

Your blood pressure may drop much further. Your doctor may change the dosage.

• - Medicines that thin the blood or inhibit blood clotting, this includes: – Acetylsalicylic acid (ASA – a compound found in many medicines that lower fever and relieve pain).

• – Heparin.

• – Coumarin-type anticoagulants, such as warfarin or phenprocoumon.

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• – Non-steroidal antiinflammatory drugs.

• – Non-selective phosphodiesterase inhibitors such as pentoxifylline.

• – Selective phosphodiesterase 3 (PDE 3) inhibitors, such as cilostazol or anagrelide.

• – Ticlopidine.

• – Clopidogrel.

• – Glycoprotein IIb/IIIa antagonists, such as:

• Abciximab.
• Eptifibatide.
• Tirofiban.
• Defibrotide.

Your doctor will monitor you carefully. Before taking any medicine ask your doctor or pharmacist, who has more information on medicines to be careful with or avoid when using Iloprost.

Iloprost with food and drink

Food or drink is not expected to affect Iloprost. However, you should avoid taking food or drink during inhalation.

Pregnancy

• - If you suffer from pulmonary hypertension, avoid getting pregnant as pregnancy may lead to a worsening of your condition and may even endanger your life.

• - If you could get pregnant, use reliable contraception from the time you start treatment and during treatment.

• - If you are pregnant, think you may be pregnant or are planning to have a baby, tell your doctor straight away. Iloprost should only be used during pregnancy if your doctor decides that the potential benefit outweighs the potential risk to you and the foetus.

Breast-feeding

It is not known whether Iloprost passes into human milk. A potential risk to the breast-feeding child cannot be excluded and it is preferable to avoid breastfeeding during Iloprost therapy.

Ask your doctor or pharmacist for advice before taking any medicine.

Newborns, infants and pregnant women should not be in the same room while you are inhaling Iloprost.

Driving and using machines

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.

Iloprost contains ethanol

This medicine contains 1.5 mg of alcohol (ethanol) in each ampoule which is equivalent to 1.62 mg/ml (96% ethanol v/v). The amount in 1 ml of this medicine is equivalent to less than 1 ml beer or 1 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects.

3. How to use Iloprost

Iloprost therapy should only be initiated by a physician experienced in treatment of pulmonary hypertension.

The following information is intended for healthcare professionals only

Instructions for use and handling

Patients stabilised on one nebuliser should not switch to another nebuliser without close supervision by the treating doctor as different nebulisers have been shown to produce aerosols with slightly different physical characteristics and may have faster delivery of the solution (see section 5.2 of the Summary of Product Characteristics).

To minimise accidental exposure, it is recommended to keep the room well ventilated.

• - Breelib

When using the Breelib nebuliser please follow the instructions for use provided with the device. Fill the medication chamber with Iloprost immediately before use.

Device	Drug product	Dose of iloprost at mouthpiece	Estimated inhalation time
Breelib	Iloprost 20 mcg/ml	5 mcg	3 minutes

How much to inhale and for how long Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

The dose of Iloprost and the duration of treatment that is right for you depend on your individual condition. Your doctor will advise you. Do not change the recommended dose without consulting your doctor first.

Different nebuliser devices can be used to administer Iloprost 20 microgram/ml.

• - Breelib nebuliser

If you are starting Iloprost treatment or if you switch from an alternative device your first inhalation will be with Iloprost 10 microgram/ml. If you tolerate this dose well, your next inhalation will be with Iloprost 20 microgram/ml. You should continue on this dose.

If you cannot tolerate inhalation of Iloprost 20 microgram/ml talk to your doctor who may decide that you should take Iloprost 10 microgram/ml.

Most people will have 6 – 9 inhalation sessions spread throughout the day. One inhalation session with Breelib will usually last about 3 minutes.

Your doctor will supervise your treatment when you start using the Breelib nebuliser to ensure that you tolerate dose and speed of inhalation well.

• - I-Neb AAD nebuliser

As you repeatedly experience extended inhalation treatment times with Iloprost 10 microgram/ml, your doctor decided to switch to Iloprost 20 microgram/ml. Iloprost 20 microgram/ml is double the concentration of Iloprost 10 microgram/ ml. The active substance can be delivered more rapidly to your lungs. Your doctor will supervise your treatment if switching from Iloprost 10 microgram/ml to Iloprost 20 microgram/ml to monitor how well you tolerate the higher concentration.

You should administer the dose 6 – 9 times per day according to individual needs and tolerability. Depending on your individual needs, Iloprost can be used for long term treatment.

• - I-Neb AAD

The I-Neb AAD System is a portable, hand-held, vibrating mesh technology nebuliser system. This system generates droplets by ultrasound, which forces the solution through a mesh.

This nebuliser monitors the breathing pattern to determine the aerosol pulse time required to deliver the pre-set dose of 5 microgram iloprost of the Iloprost 20 mcg/ml nebuliser solution. The nebulising device delivers 5 microgram iloprost at the mouthpiece. The Mass Median Aerodynamic Diameter (MMAD) of the aerosol is between 1 and 5 micrometers.

When using the I-Neb AAD system the following instructions need to be followed. The dose delivered by the I-Neb AAD system is controlled by the medication chamber in combination with a control disc.

For each medication chamber there is a corresponding colour coded control disc. For each inhalation session with the I-Neb AAD, the content of one 1 ml ampoule of Iloprost 20 microgram/ml you tolerate the treatment.

If you feel that the effect of Iloprost is too strong or too weak, talk to your doctor or pharmacist.

Ask your doctor to have someone help you become thoroughly familiar with the use of the nebuliser. You should not switch to another nebuliser without consulting the doctor who is treating you. How to inhale

For each inhalation session you should use a new ampoule of Iloprost. Just before you start to inhale, break the glass ampoule and pour the solution into the medication chamber following the instructions for use of the nebuliser.

Follow carefully the instructions that come with the nebuliser especially the instructions on hygiene and cleaning of the nebuliser.

Always take Iloprost exactly as your doctor has told you.

• – Iloprost 20 microgram/ml nebuliser solution is inhaled using the nebulisers your doctor prescribed (either the Breelib or the I-Neb AAD nebuliser).

• – The nebuliser turns Iloprost solution into a mist which you breathe in through your mouth.

• – For the inhalation you should use a mouthpiece to prevent Iloprost coming into contact with your skin. Do not use a facial mask.

• – Follow carefully any instructions that come with the nebuliser. Check with your doctor or pharmacist if you are unsure.

• – Any Iloprost solution remaining in the nebuliser after inhalation must be thrown away (see section 5).

Room ventilation

Be sure to ventilate or air the room in which you have taken your Iloprost treatment. Other people might accidentally be exposed to Iloprost through the room air. In particular, newborns, infants and pregnant women should not be in the same room while you are inhaling Iloprost.

• - Breelib

Fill the medication chamber with Iloprost immediately before use. For filling please follow the instructions for use of the nebuliser.

Device	Drug product	Dose of iloprost at mouthpiece	Estimated inhalation time
Breelib	Iloprost 20 mcg/ml	5 mcg	3 minutes

• - I-Neb AAD

• 1. Just before you start to inhale, break the glass ampoule of Iloprost 20 mcg/ ml and pour the complete contents of 1 ml into the nebuliser medication golden chamber.

• 2. The pre-set dose provided by the I-Neb AAD system is controlled by the medication chamber in combination with a control disc.

For Iloprost 20 microgram/ml (5 microgram dose) , the medication chamber with the golden coloured latch is used together with the golden control disc.

• 3. To ensure that you receive the prescribed dose, check the colour of the medication chamber and the colour of the control disc. They should both have the same colour.

Since the I-Neb AAD nebuliser can be used for Iloprost 10 microgram/ml and Iloprost 20 microgram/ ml, the table below provides a summary of the user instructions of the I-Neb for the 2 concentrations of Iloprost:

Drug product	Dosage	I-Neb AAD
		Medication chamber latch	Control disc
Iloprost 10 mcg/ml	2.5 mcg	red	red
	5 mcg	purple	purple
Iloprost 20 mcg/ml	5 mcg	golden	golden

For further details please refer to the instruction manual of the nebuliser device or ask your doctor.

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If you use more Iloprost than you should

Using more Iloprost than you should may lead to dizziness, headache, flushing (reddening of the face), nausea (feeling sick), jaw pain or back pain. You may also experience a decrease or an increase in blood pressure, bradycardia (reduced heart rate), tachycardia (increased heart rate), vomiting, diarrhoea or limb pain. If any of these happen when you have used more Iloprost than you should: – Stop the inhalation session.

• – Talk to your doctor.

Your doctor will monitor you and treat any resulting symptoms. A specific antidote is not known.

If you forget to use Iloprost

Do not take a double dose to make up for a forgotten dose. Please ask your doctor what you should do.

If you stop taking Iloprost

If you stop or wish to stop treatment, discuss it with your doctor first.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following serious side effects may occur. In this case talk to your doctor immediately.

Very common (may affect more than

1 in 10 people):

– Bleeding events (mostly nosebleed (epistaxis) and coughing up blood (haemoptysis)) may very commonly occur, especially if you are also taking blood-thinning medicines (anticoagulants). The risk of bleeding may be increased in patients when inhibitors of platelet aggregation or anticoagulants are given at the same time (see also section 2). Very rarely, fatal cases including bleeding in the brain (cerebral and intracranial haemorrhage) have been reported.

Common (may affect up to

1 in 10 people):

• – Fainting (syncope) is a symptom of the illness itself but can also occur during treatment with iloprost (see also section 2 “Warnings and precautions”, for advice on what you can do to avoid this).

• – Low blood pressure (hypotension).

Not known (cannot be estimated from the available data):

• – Bronchospasm (sudden constriction of the muscles in the walls of the small airways) and wheezing (see also section 2 “Warnings and precautions”).

Below we list other possible side effects by how likely they are:

Very common (may affect more than

• 1 in 10 people):

• – Widening of the blood vessels (vasodilatation). Symptoms can be flushing or reddening of the face.

• – Chest discomfort / chest pain.

• – Coughing.

• – Headache.

• – Nausea.

• – Pain in jaw / spasm of the jaw muscles (trismus).

• – Swelling of the limbs (peripheral oedema).

Common (may affect up to

1 in 10 people):

• – Breathing difficulties (dyspnoea).

• – Dizziness.

• – Vomiting.

• – Diarrhoea.

• – Pain when swallowing (pharyngolaryngeal irritation).

• – Throat irritation.

• – Mouth and tongue irritation including pain.

• – Rash.

• – Fast heartbeat (tachycardia).

• – Awareness of fast or hard heartbeat (palpitations).

Not known (frequency cannot be estimated from the available data): – Reduction in the number of blood platelets (thrombocytopenia).

• – Hypersensitivity (i.e. allergy).

• – Disturbed sense of taste (dysgeusia).

Other possible effects

• – Swelling, mainly of the ankles and legs, due to fluid retention (peripheral oedema) is a very common symptom of the illness itself but can also occur during treatment with iloprost.

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 the Yellow Card Scheme at: 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.

Marketing Authorisation Holder Zentiva Pharma UK Limited, 12 New Fetter Lane, London, EC4A 1JP, UK

Manufacturer

Zentiva, k.s., U kabelovny 130,

Dolni' Mecholupy, 102 37, Prague 10, Czech Republic

This leaflet was last revised in January 2021

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 wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Iloprost contains

• - The active substance is iloprost.

Each ampoule with 1 ml contains 20 microgram iloprost (as iloprost trometamol).

• - The other ingredients are trometamol, ethanol 96%, sodium chloride, hydrochloric acid for pH adjustment, and water for injection.

What Iloprost looks like and contents of the pack

Iloprost is clear and colourless solution free of visible particles for inhalation with the Breelib or the I-Neb nebuliser.

Iloprost is available in packs containing: 30×1 ml (6 blisters with 5 ampoules). 42×1 ml (8 blisters with 5 ampoules and 1 blister with 2 ampoules).

168×1 ml (33 blisters with 5 ampoules and 1 blister with 3 ampoules).

Multipacks containing 160 ampoules (4 inner boxes containing 8 blisters with 5 ampoules).

Not all pack sizes may be marketed.

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will be transferred into the appropriate of iloprost solution, have not nebuliser medication chamber with been established.

golden coloured latch together with the golden colour disc immediately before use.

Since the I-Neb AAD system can be used for Iloprost 10 microgram/ml and Iloprost 20 microgram/ml, the table below provides a summary of the user instructions of the I-Neb for the 2 concentrations of Iloprost:

Drug product	Dosage	I-Neb AAD
		Medication chamber latch	Control disc
Iloprost 10 mcg/ml	2.5 mcg	red	red
	5 mcg	purple	purple
Iloprost 20 mcg/ml	5 mcg	golden	golden

The efficacy and tolerability of inhaled iloprost when administered with other nebulising systems, which provide different nebulisation characteristics