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PACKAGE LEAFLET: INFORMATION FOR THE USER    saraoooLrooo

Epoprostenol Sodium 0.5 mg Powder and Solvent for Solution for Infusion Epoprostenol Sodium 1.5 mg Powder and Solvent for Solution for Infusion

Epoprostenol

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 or 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 or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Epoprostenol is and what it is used for

2.    What you need to know before you use Epoprostenol

3.    How to use Epoprostenol

4.    Possible side effects

5.    How to store Epoprostenol

6.    Contents of the pack and other information

What Epoprostenol is and what it is used for

Epoprostenol contains the active substance epoprostenol which belongs to a group of medicines called prostaglandin, which stops blood from clotting and widens the blood vessels.

Epoprostenol is used to treat a lung condition called ‘pulmonary arterial hypertension'. This is where the pressure is high in the blood vessels in the lungs. Epoprostenol widens the blood vessels to lower the blood pressure in the lungs.

Epoprostenol is used to prevent blood clotting during kidney dialysis when heparin cannot be used.

2 What you need to know before you use Epoprostenol

Do not use Epoprostenol

•    if you are allergic to epoprostenol or any of the other ingredients of this medicine (listed in section 6).

•    if you have heart failure.

•    if you start to develop a build-up of fluid in your lungs causing breathlessness after starting this treatment.

If you think any of these apply to you, don’t take Epoprostenol until you have checked with your doctor.

Warnings and precautions

Before you are given Epoprostenol your doctor needs to know:

•    if you have any problems with bleeding.

Skin damage at the injection site

Epoprostenol is injected into a vein. It is important that the medicine does not leak out of the vein into the surrounding tissue. If it does, the skin could be damaged. The symptoms of this are:

•    tenderness

•    burning

•    stinging

•    swelling

•    redness.

This may be followed by blistering and shedding of the skin. While you are being treated with Epoprostenol it is important that you check the injection area.

Contact the hospital immediately for advice if the area becomes sore, painful or swollen or you notice any blistering or shedding.

Effect of Epoprostenol on blood pressure and heart rate

Epoprostenol can cause your heart to beat faster or slower. Also your blood pressure can become too low. While you are being treated with Epoprostenol your heart rate and blood pressure will be checked. The symptoms of low blood pressure include dizziness and fainting.

Tell your doctor if you get these symptoms. Your dose may need to be reduced or your infusion stopped.

Other medicines and Epoprostenol

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

Some medicines may affect how Epoprostenol works, or make it more likely that you'll have side effects. Epoprostenol can also affect how some other medicines work if taken at the same time.

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These include:

•    medicines used to treat high blood pressure

•    medicines used to prevent blood clots

•    medicines used to dissolve blood clots

•    medicines to treat inflammation or pain (also called ‘NSAIDs')

•    digoxin (used to treat heart disease).

Tell your doctor or pharmacist if you are taking any of these.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine as your symptoms could worsen during pregnancy.

It is not known whether the ingredients of Epoprostenol can pass into breast-milk. You should stop breast-feeding your child during treatment with Epoprostenol.

Driving and using machines

Your treatment may have an effect on the ability to drive or use machinery.

Don’t drive or use machines unless you're feeling well.

Epoprostenol contains sodium

Epoprostenol Sodium 0.5 mg Powder and Solvent for Solution for Infusion contains 2.4 mmol (or 54.7 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Epoprostenol Sodium 1.5 mg Powder and Solvent for Solution for Infusion contains 2.4 mmol (or 54.8 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

How to use Epoprostenol

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor will decide how much Epoprostenol is right for you. The amount you are given is based on your body weight, and your type of illness. Your dose may be increased or decreased depending on how well you respond to treatment.

Epoprostenol is given by slow infusion (drip) into a vein.

Pulmonary arterial hypertension

Your first treatment will be given to you in a hospital. This is because your doctor needs to monitor you and find the best dose for you.

You will start with an infusion of Epoprostenol. The dose will be increased, until your symptoms are relieved, and any side effects are manageable.

Once the best dose has been found, a permanent tube (line) will be fitted into one of your veins. You can then be treated using an infusion pump.

Kidney dialysis

You will be given an infusion of Epoprostenol for the duration of your dialysis.

Using Epoprostenol at home (only for treatment of Pulmonary Arterial Hypertension)

If you are treating yourself at home, your doctor or nurse will show you how to prepare and use Epoprostenol. They will also advise you how to stop treatment if necessary. Stopping Epoprostenol must be done gradually. It is very important that you follow all their instructions carefully.

Continued on the next page >>

The following information is intended for medical or healthcare professionals only 7. INFORMATION FOR HEALTHCARE PROFESSIONALS Renal Dialysis

There is only one pack available for use in renal dialysis:

One 0.5 mg powder vial and one solvent vial Reconstitution:

1.    Use only the solvent provided for reconstitution

2.    Withdraw approximately 10mL of the solvent into a sterile syringe, inject it into the vial containing 0.5 mg freeze-dried Epoprostenol powder and shake gently until the powder has dissolved

3.    Draw up the resulting Epoprostenol solution into the syringe, re-inject it into the remaining volume of the solvent and mix thoroughly.

This solution is now referred to as the concentrated solution and contains 10,000 nanogram per mL Epoprostenol. Only this concentrated solution is suitable for further dilution prior to use. When 0.5 mg Epoprostenol powder is reconstituted with 50 mL of the solvent, the final injection has a pH of approximately 10.5 and a sodium ion content of approximately 54.7 mg.

Dilution:

The concentrated solution is normally further diluted before use. It may be diluted with sodium chloride 0.9% w/v solution, provided a ratio of 6 volumes of sodium chloride 0.9% w/v solution to 1 volume of concentrated solution is not exceeded e.g. 50 mL of concentrated solution further diluted with a maximum of 300 mL sodium chloride 0.9% w/v solution.

Other common intravenous fluids are unsatisfactory for the dilution of the concentrated solution as the required pH is not attained. Epoprostenol solutions are less stable at low pH.

To dilute the concentrated solution, draw it up into a larger syringe and then attach the sterile filter provided to the syringe.

Dispense the concentrated solution directly into the chosen infusion solution using firm but not excessive pressure; the typical time taken for filtration of 50 mL of concentrated solution is 70 seconds. Mix well.

The filter unit must be used once only and then discarded.

When reconstituted and diluted as directed above, Epoprostenol infusion solutions have a pH of approximately 10 and will retain 90% of their initial potency for approximately 12 hours at 25°C.

Calculation of infusion rate:

The infusion rate may be calculated from the following formula:

Infusion rate = dosage (nanogram/kg/min) x bodyweight (kg)

(mL/min)    concentration of solution (nanogram/mL)

Infusion rate (mL/h) = Infusion rate (mL/min) x 60

For administration using a pump capable of delivering small volume constant infusions, suitable aliquots of concentrated solution may be diluted with sterile sodium chloride 0.9% w/v solution.

Pulmonary arterial hypertension

There are four packs available for use in the treatment of pulmonary arterial hypertension, as follows:

One 0.5 mg powder vial and one or two solvent vials and a filter unit.

One 1.5 mg powder vial and one or two solvent vials and a filter unit.

One 0.5 mg powder vial.

One 1.5 mg powder vial.

Not all pack sizes are available in all markets.

Initially, a pack containing solvent must be used. During chronic therapy with Epoprostenol the final concentration of solution may be increased by the addition of a further 0.5 mg or 1.5 mg vial of freeze-dried Epoprostenol.

Only vials of the same amount as that included in the initial starter pack may be used to increase the final ^{concentration of solution}.    SZoooooLTooo Continued on the next page >>

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Epoprostenol comes as a powder in a glass vial. Before use, the powder needs to be dissolved in the liquid provided. The liquid does not contain a preservative. If you have any of the liquid left over, it must be thrown away.

Looking afterthe injection line

If you have been fitted with a ‘line’ into a vein it is very important to keep this area clean, otherwise you could get an infection. Your doctor or nurse will show you how to clean your ‘line’ and the area around it. It is very important that you follow all of their instructions carefully.

Ifyou use more Epoprostenol than you should Seek urgent medical attention if you think you have used or been given too much Epoprostenol. Symptoms of overdose may include headache, nausea, vomiting, fast heart rate, warmth or tingling, or feeling like you might pass out (feeling faint/dizziness).

If you forget to use Epoprostenol

Do not take a double dose to make up for a forgotten dose.

Ifyou stop using Epoprostenol

Stopping Epoprostenol must be done gradually. If the treatment is stopped too quickly you may get serious side effects, including dizziness, feeling weak and breathing difficulties. If you have problems with the infusion pump or injection line that stops, or prevents treatment with Epoprostenol, contact your doctor, nurse or hospital immediately.

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

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: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5

How to store Epoprostenol

Keep this medicine out of the sight and reach of children.

Powder for solution for infusion: Keep the vial in the outer carton in order to protect from light.

Solvent: Do not freeze.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

The reconstituted solution should not be used if particles are present. Glycine buffer diluent contains no preservative, consequently a vial should be used once only and then discarded.

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.

Contents of the pack and other information

4

Possible side effects

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

Tell your doctor or nurse immediately, as these may be signs of infection of the blood or low blood pressure or serious bleeding:

•    You feel that your heart is beating faster, or you have chest pain or shortness of breath.

•    You feel dizzy or feel faint, especially on standing.

•    You have fevers or chills.

•    You have more frequent, or longer periods of bleeding.

Talk to your doctor or pharmacist or nurse about any other side effects, including those not listed in this leaflet.

Very common side effects (may affect more than 1 in 10 people):

•    headache

•    redness of your face

•    feeling sick (nausea)

•    being sick (vomiting)

•    diarrhoea

•    jaw pain

•    pain

Common side effects (may affect up to 1 in10 people):

•    infection of the blood (septicaemia)

•    bleeding at various sites and bruising more easily than normal, for example from the nose or gums

•    feeling anxious, feeling nervous

•    heart beating faster

•    slow heart beat

•    stomach discomfort or pain

•    rash

•    joint pain

•    pain at the injection site

•    chest pain

•    low blood pressure

Common side effects that may show up in blood tests

•    decrease in the number of blood platelets (cells that help the blood to clot)

Uncommon side effects (may affect up to 1 in 100 people):

•    dry mouth

•    sweating

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

•    infection at the injection site

Very rare side effects (may affect up to 1 in 10,000 people):

•    feeling agitated

•    pale skin

•    redness at the injection site

•    feeling tired, weak

•    feeling of tightness around the chest

•    overactive thyroid gland

•    blockage of the injection catheter

Other side effects

It is not known how many people are affected:

•    build up of fluid in the lungs (pulmonary oedema)

•    increase in sugar (glucose) in the blood

What Epoprostenol contains Epoprostenol Sodium 0.5 mg Powder and Solvent for Solution for Infusion

•    The active substance is epoprostenol (as epoprostenol sodium). Each vial contains epoprostenol sodium equivalent to 0.5 mg epoprostenol.

One ml of reconstituted concentrate solution contains epoprostenol (as epoprostenol sodium)

10.000    nanogrammes.

Epoprostenol Sodium 1.5 mg Powder and Solvent for Solution for Infusion

•    The active substance is epoprostenol (as epoprostenol sodium). Each vial contains epoprostenol sodium equivalent to 1.5 mg epoprostenol.

One ml of reconstituted concentrate solution contains epoprostenol (as epoprostenol sodium)

30.000    nanogrammes.

•    The other ingredients are: Mannitol, Glycine, Sodium Chloride, Sodium Hydroxide (only for pH adjustment).

The solvent for Epoprostenol is composed of sodium chloride, glycine, sodium hydroxide (only for pH adjustment) and water for injection.

What Epoprostenol looks like and contents of the pack

Powder for solution for infusion: 15 ml colourless glass type I vials closed with rubber stopper and aluminium/propylene cap

Solvent: 55 ml colourless glass type I vials closed with rubber stopper and aluminium/propylene cap.

Pack sizes:

•    1,2,3,4,5, 6 or 10 packs containing 1 vial with powder for solution for infusion, 1 vial with solvent and 1 filter;

•    1, 2, 3, 4, 5, 6 or 10 packs containing 1 vial with powder for solution for infusion, 2 vials with solvent and 1 filter.

The powder needs to be reconstituted and diluted before infusion.

Marketing Authorisation Holder

Sandoz Ltd, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, UK.

Manufacturer

Lek Pharmaceuticals d.d., Verovskova 57, 1526 Ljubljana, Slovenia,

This leaflet was last revised in 03/2015.

Other sources of information

SZ07701 LT03A

Reconstitution:

1.    Use only the solvent provided for reconstitution.

2.    Withdraw approximately 10mL of the solvent into a sterile syringe, inject the contents of the syringe into the vial containing Epoprostenol powder and shake gently until the powder has dissolved.

3.    Draw up the resulting Epoprostenol solution into the syringe, re-inject it into the remaining volume of the solvent and mix thoroughly.

This solution is now referred to as the concentrated solution and contains either 10,000 (for the 0.5 mg strength) or 30,000 nanogram per mL Epoprostenol (for the 1.5 mg strength). Only this concentrated solution is suitable for further dilution prior to use. When 0.5 mg Epoprostenol powder is reconstituted with 50 mL of the solvent, the final injection has a pH of approximately 10.5 and a sodium ion content of approximately 54.8 mg.

Dilution:

Epoprostenol may be used either as concentrated solution or in a diluted form for the treatment of pulmonary arterial hypertension. Only the solvent provided may be used for the further dilution of reconstituted Epoprostenol. Sodium chloride 0.9% w/v solution must not be used when Epoprostenol is to be used for the treatment of pulmonary arterial hypertension.

To dilute the concentrated solution, draw it up into a larger syringe and then attach the sterile filter provided to the syringe.

Dispense the concentrated solution directly into the solvent using firm but not excessive pressure; the typical time taken for filtration of 50 mL of concentrated solution is 70 seconds. Mix well.

The filter must be used once only and then discarded.

Concentrations commonly used in the treatment pulmonary arterial hypertension are as follows:

•    5,000 nanogram/mL - One vial containing 0.5 mg Epoprostenol reconstituted and diluted to a total volume of 100 mL in solvent.

•    10,000 nanogram/mL-Two vials containing 0.5 mg Epoprostenol reconstituted and diluted to a total volume of 100 mL in solvent.

•    15,000 nanogram/mL-One vial containing 1.5 mg Epoprostenol reconstituted and diluted to a total volume of 100 mL in solvent.

Calculation of infusion rate:

The infusion rate may be calculated from the following formula:

Infusion rate = dosage (nanogram/kg/min) x bodyweight (kg)

(mL/min)    concentration of solution (nanogram/mL)

Infusion rate (mL/h) = Infusion rate (mL/min) x 60

Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of Epoprostenol.

Special precautions for storage

Don’t store above 25°C.

Keep container in the outer carton to protect from light.

Keep dry.

Do not freeze.

Any cold pouch used must be capable of maintaining the temperature of the reconstituted solution.

Store between 2 and 8°C for the full administration period.

Reconstitution and dilution should be carried out immediately prior to use. The solvent contains no preservative; consequently a vial should be used once only and then discarded.

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