Epoprostenol 0.5 mg powder and solvent for solution for infusion – patient leaflet, side effects, dosage

1. 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 take Epoprostenol

Do not take 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

Talk to your doctor or nurse before taking Epoprostenol:

• If you have any problems with bleeding.
• if you are on a controlled sodium diet.

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 or pharmacist if you are taking, have recently taken or might take 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. 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, NSAID’s)
• 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

This medicinal product contains 1.3 mmol (or 30 milligrams) sodium (main component of cooking/table salt) in each dose. This is equivalent to 1.50% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to take 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. 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 after the 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.

If you take 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 take Epoprostenol

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

Infusion rate (ml/min) dosage (ng/kg/min) x bodyweight (kg)

concentration of solution (ng/ml) =

Infusion rate (ml/min) x 60 =

The following information is intended for medical or healthcare professionals only:

Infusion rate (ml/h)

PAGE 1 OF 2 Dimension: 190 x 420 mm Commodity No.: N/A

AMS Component No.: AW-LF-0000446

(v0.7)

Product Description: Epoprostenol 0.5 mg Pdr fr Inf UK 1Vial

Component: Leaflet

Product Code: 101934

Country: UK

Vendor Name: Karmed

Revision Date: 26-May-2025 Revised by: NRV

and technical approval needs to be taken, from the CMO, before Implementation. Primary and secondary Pulmonary Hypertension

The following pack unit is available for use in the treatment of primary pulmonary hypertension:

One vial containing sterile freeze-dried epoprostenol sodium equivalent to 0.5 mg epoprostenol supplied with one 50 ml vial of sterile Glycine Buffer Diluent solution.

Initially a pack unit containing diluent buffer must be used. During chronic epoprostenol therapy 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.

Reconstitution:

This should be carried out according to the instructions given for renal dialysis. Where a pack containing 0.5 mg epoprostenol is reconstituted with 50 ml sterile diluent the resultant concentration is 10,000 nanograms per ml. Dilution:

Epoprostenol 0.5 mg may be used either as concentrated solution or in a diluted form for the treatment of PPH/SPH. Only the Glycine Buffer Diluent provided may be used for the further dilution of reconstituted Epoprostenol 0.5 mg. Physiological saline must not be used when Epoprostenol 0.5 mg is to be used for the treatment of primary pulmonary hypertension.

Concentrations commonly used in the treatment of primary or secondary pulmonary hypertension are as follows:

• 15,000 ng/ml – 3vials of 0.5mg epoprostenol or one vial of 1.5mg

  epoprostenol reconstituted and diluted to a total volume of 100ml in the Glycine Buffer Diluent.

• 10,000 ng/ml – two vials containing 0.5mg epoprostenol reconstituted

  and diluted to a total volume of 100ml in the Glycine Buffer Diluent. The maximum recommended concentration for administration in primary pulmonary hypertension is 60,000ng/ml.

Epoprostenol 0.5 mg must not be administered with other parenteral solutions or medications when used for primary or secondary pulmonary 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 pump cassette using firm but not excessive pressure; the typical time taken for filtration of 50 ml of concentrated solution is 70 seconds.

Remove the filter from the syringe and draw up the additional volume of the Glycine Buffer Diluent required to achieve the desired dilution. Refit the filter to the syringe and dispense the additional buffer through this into the concentrated Epoprostenol 0.5 mg solution in the cassette. Mix well.

The filter unit must be used for the dilution of one pack only and then discarded.

The ambulatory pump used to administer Epoprostenol 0.5 mg should (1)

be small and lightweight, (2) be able to adjust infusion rates in ng/kg/min increments, (3) have occlusion, end of infusion, and low battery alarms, (4) be accurate to ± 6% of the programmed rate (5) be positive pressure driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver Epoprostenol 0.5 mg, and (6) include a cold pouch system. The reservoir should be made of polyvinyl chloride, polypropylene, or glass.

Protect infusion bags from light during infusion.

CALCULATION OF INFUSION RATE:

The infusion rate may be calculated from the formula given above for renal dialysis.

An example of a concentration commonly used in primary or secondary pulmonary hypertension is shown below.

Infusion rates for a concentration of 15,000 nanograms/ml: Concentration of solution = 15,000 ng/ml epoprostenol

Flow rates in ml/hr

If you stop taking 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.

4. Possible side effects

Like all medicines, this medicine 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.

Other possible side effects include:

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

• Headache
• Jaw pain
• Pain
• Being sick (vomiting)
• Feeling sick (nausea)
• Diarrhoea
• Redness of your face (flushing)

Common side effects: These may affect up to 1 in 10 people

• Infection of the blood (septicaemia)
• Heart beating faster
• Slow heart beat
• Low blood pressure

• Bleeding at various sites and bruising more easily than normal, for

  example from the nose or gums

• Stomach discomfort or pain
• Chest pain
• Joint pain
• Feeling anxious, feeling nervous
• Rash
• Pain at the injection site

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: These may affect up to 1 in 100 people
• Sweating
• Dry mouth

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

• Infection at the injection site

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

• Feeling of tightness around the chest
• Feeling tired, weak
• Feeling agitated
• Pale skin
• Redness at the injection site
• Overactive thyroid gland
• Blockage of the injection catheter

Other side effects: It is not known how many people are affected (frequency cannot be estimated from the available data):

• Enlarged or overactive spleen
• Build up of fluid in the lungs (pulmonary oedema)
• Increase in sugar (glucose) in the blood
• Swelling due to build up of fluid around the stomach

• Too much pumping of blood form the heart leading to shortness of

  breath, fatigue, swelling of the legs and abdomen due to fluid build-up, persistent cough.

Reporting of side effects

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. You can also report side effects directly via the Yellow Card Scheme. Website: 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.

5. How to store Epoprostenol

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. The expiry date refers to the last day of that month.

Powder for solution for infusion:

Keep the vial in the outer carton in order to protect from light. Keep the vial tightly closed in order to protect from moisture. Store below 25°C

Solvent:

Keep the vial in the outer carton in order to protect from light. Store below 25°C

Shelf-life after reconstitution:

Pulmonary arterial hypertension

Once Epoprostenol powder has been dissolved, and diluted, it should ideally be used immediately. If you are being given Epoprostenol using an infusion pump, a ‘cold pouch’ may be used to maintain the temperature of the solution. When using a ‘cold pouch’, the solution can be stored in the pump for up to 24 hours at 2-8°C if necessary. The cold pouch must be regularly changed throughout the day, to maintain the temperature of the solution. If you are not using a ‘cold pouch’, the solution can be stored in the pump:

• for up to 12 hours at 25°C, if it has just been made up
• for a maximum of 8 hours if it was made previously and has been stored at 2-8°C.

Renal Dialysis:

Once Epoprostenol has been dissolved and diluted, any unused solution can be stored at 25°C and used within 12 hours.

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 to protect the environment.

6. Contents of the pack and other information

What Epoprostenol contains

Powder for solution for infusion

• The active substance is Epoprostenol (as Sodium).

  1 vial contains 0.531 milligrams Epoprostenol Sodium, corresponding to 0.5 milligrams Epoprostenol.

• The other ingredients are:

  Powder for solution for infusion: Mannitol, Glycine, Sodium Chloride, Sodium Hydroxide (for pH adjustment)

  Solvent: Glycine, Sodium Chloride, Sodium Hydroxide (for pH adjustment), Water for Injection

When 1 vial with 0.5 mg epoprostenol is reconstituted with 50 ml of sterile buffer, the resultant concentration is 10,000 nanograms per ml. Solvent

Each vial of solvent contains 50 ml of a sterile glycine buffer solution containing approximately 28.9 milligram sodium.

What Epoprostenol looks like and contents of the pack

Epoprostenol is a white lyophilised powder cake packed in clear glass vials with grey lyo stopper and aluminium caps with blue flip-off inserts. The solvent is a clear, colourless solution packed in clear glass vials. After reconstitution Epoprostenol is a colourless solution, practically free of particles.

Each pack unit contains

• one vial Epoprostenol 0.5 mg, containing a white freeze-dried powder cake packed in a 15 ml clear glass vial Type I with grey lyo stopper and aluminium caps with blue flip-off inserts.
• one 50ml sterile Glycine buffer solution, pH 10.5 in a clear glass vial
• one single unit sterile filter device for aseptic preparation of infusion solution

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Mercury Pharmaceuticals Ltd., Dashwood House, 69 Old Broad Street, London, EC2M 1QS, United Kingdom

Manufacturer

Prestige Promotion Verkaufsförderung & Werbeservice GmbH Lindigstraße 6

D-63801 Kleinostheim

This leaflet was last revised in May 2025

AW-LF-0000446 (v0.7)

PAGE 2 OF 2 Dimension: 190 x 420 mm Commodity No.: N/A

AMS Component No.: AW-LF-0000446

(v0.7)

Product Description: Epoprostenol 0.5 mg Pdr fr Inf UK 1Vial

Component: Leaflet

Product Code: 101934

Country: UK

Vendor Name: Karmed

Revision Date: 26-May-2025 Revised by: NRV

and technical approval needs to be taken, from the CMO, before Implementation.