EPOPROSTENOL SUN 1.5 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Epoprostenol SUN 0.5 mg powder for solution for infusion

Epoprostenol SUN 1.5 mg powder 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, 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Epoprostenol SUN and what is it used for
2. What you need to know before you use Epoprostenol SUN
3. How to use Epoprostenol SUN
4. Possible side effects
5. Storage of Epoprostenol SUN
6. Contents of the pack and other information

1. What is Epoprostenol SUN and what is it used for

Epoprostenol Sun contains the active substance epoprostenol, which belongs to a group of medicines called prostaglandins, which prevent blood clotting and widen blood vessels.

Epoprostenol Sun is used to treat a lung disease known as "pulmonary arterial hypertension". This occurs when the pressure of the blood vessels in the lungs is high. Epoprostenol Sun widens the blood vessels to decrease the blood pressure in the lungs.

Epoprostenol Sun is also used to prevent blood clotting during kidney dialysis in emergency situations where heparin cannot be used.

2. What you need to know before you use Epoprostenol SUN

Do not use Epoprostenol Sun

• if you are allergicto epoprostenol or any of the other ingredients of this medicine (listed in section 6)
• if you have heart failure.
• if you start to develop fluid accumulation in the lungs that causes difficulty breathing after starting treatment.

If you think any of these situations apply to you, do not use Epoprostenol Sununtil you have consulted your doctor.

Warnings and precautions

Consult your doctor before starting to use Epoprostenol Sun

• if you bleed easily(e.g. from the nose).

Skin and injection site damage

Epoprostenol Sun is injected into a vein. It is essential that the medicine does not leak or spill out of the vein into the surrounding tissues. If it does, it can damage the skin. The symptoms are:

• sensitivity
• burning
• itching
• swelling
• redness.

This can be followed by blistering and peeling of the skin. It is essential that you monitor the injection site while being treated with Epoprostenol Sun.

Contact the hospital immediatelyif the injection site becomes painful, itchy, or inflamed, or if you notice any blistering or peeling of the skin.

Effect of Epoprostenol Sun on blood pressure and heart rate

Epoprostenol Sun can speed up or slow down your heart rate. Your blood pressure may also become very low. While being treated with Epoprostenol Sun, your heart rate and blood pressure will be monitored. The symptoms of low blood pressure include dizzinessand fainting.

Tell your doctorif you have any of these symptoms. It may be necessary to decrease your dose or interrupt the infusion.

Children and adolescents

The safety and efficacy of Epoprostenol Sun in children have not been established.

Using Epoprostenol Sun with other medicines

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines.

Some medicines may affect how Epoprostenol Sun works or make it more likely that you will get side effects.

Epoprostenol Sun may also affect how 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 used to treat inflammation or pain(also called NSAIDs), e.g. ibuprofen
• digoxin (used to treat heart conditions).

Tell your doctor or nurseif you are taking any of these medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

It is not knownif the components of Epoprostenol Sun can pass into breast milk. You must stop breastfeeding while being treated with Epoprostenol Sun.

Driving and using machines

Treatment may affect your ability to drive or use machines.

Do not drive or use machinesif you do not feel well.

Epoprostenol Sun contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially "sodium-free".

The diluted solution of Epoprostenol Sun (pH 12) must not be used with administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG).

3. How to use Epoprostenol SUN

Follow exactly the administration instructions of this medicine given by your doctor, nurse, or pharmacist. If you are unsure, consult your doctor or nurse again.

Epoprostenol Sun comes as a powder in a small glass vial. The powder must be dissolved before use.

Epoprostenol Sun must not be administered as a rapid injection into the vein. It must always be administered as an intravenous infusion (drip).

Your doctor will tell you how much Epoprostenol Sun is suitable for you. The amount you are given is based on your body weight and the type of disease. Your dose may be increased or decreased depending on how well you respond to treatment.

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

Pulmonary arterial hypertension

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

You will start with an infusion of Epoprostenol Sun. The dose will be increased until your symptoms are relieved and any side effects are controlled. Once the best dose is identified, a permanent catheter (line) will be placed in one of your veins. You can then be treated using an infusion pump.

Kidney dialysis

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

Using Epoprostenol Sun at home (only for the treatment of pulmonary arterial hypertension)

If you are being treated at home, your doctor or nurse will teach you how to prepare and use Epoprostenol Sun. They will also tell you how to stop treatment if necessary. Stopping Epoprostenol Sun must be done gradually. It is very important that you carefully follow allthe instructions.

Epoprostenol Sun comes as a powder in a glass vial. Before using it, the powder must be dissolved in a liquid. The liquid does not contain preservatives. You must discard any liquid that you do not use.

Catheter care

If you have a "line" placed in a vein, it is very importantto keep the area clean; otherwise, you may get an infection. Your doctor or nurse will teach you how to clean the "line" and the surrounding area. It is very important that you carefully follow allthe instructions. It is also very importantthat you carefully follow allthe instructions regarding changing the drug reservoir of the pump (cassette) and that you always use an extension set with an internal filter, as instructed by your doctor to reduce the risk of infection.

If you use more Epoprostenol Sun than you should

Seek urgent medical attentionif you think you have used or been given too much Epoprostenol Sun. The symptoms of overdose may include headache, nausea, vomiting, fast heart rate, warmth, or tingling, or feeling like you may faint (dizziness/vertigo).

If you forget to use Epoprostenol Sun

Do not use a double dose to make up for forgotten doses.

If you stop treatment with Epoprostenol Sun

Stopping Epoprostenol Sun must be done gradually. If you stop treatment too quickly, you may have serious side effects, including dizziness, weakness, and difficulty breathing. If you have problems with the infusion pump or catheter because it stops or prevents treatment with Epoprostenol Sun, contact your doctor, nurse, or hospital immediately.

If you have any other questions about 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.

Tell your doctor or nurse immediately if you get any of the following signs of blood infection, low blood pressure, or severe bleeding:

• You feel your heart beating faster, or you have chest pain or difficulty breathing.
• You feel dizzy or faint, especially when standing up.
• You have a fever or chills.
• You bleed more easily or for longer periods, e.g. from the nose.
• The injection site becomes painful, itchy, or inflamed, or you notice any blistering or peeling of the skin (see section 2).

Other possible side effects

Very common (affect more than 1 in 10 people)

• headache
• jaw pain
• general pain
• being sick (vomiting)
• feeling sick (nausea)
• diarrhea
• flushing

Common (may affect up to 1 in 10 people)

• blood infection (septicemia)
• fast heart rate
• slow heart rate
• low blood pressure
• bleeding at various sites and increased risk of bruising, e.g. nosebleeds or gum bleeding
• discomfort or pain in the stomach
• chest pain
• joint pain
• feeling anxious or nervous
• rash
• pain at the injection site
• decrease in the number of platelets in the blood (cells that help blood clot). This may be seen in blood tests.

Uncommon (may affect up to 1 in 100 people)

• sweating
• dry mouth

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

• infection at the injection site

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

• feeling of pressure in the chest
• fatigue, weakness
• agitation
• pallor
• redness at the injection site
• overactivity of the thyroid gland
• blockage of the intravenous catheter

Frequency not known (cannot be estimated from the available data)

• enlargement or overactivity of the spleen
• fluid accumulation in the lungs (pulmonary edema)
• increased blood sugar (glucose) levels
• swelling due to fluid accumulation around the stomach
• excessive blood flow from the heart leading to difficult breathing, fatigue, swelling of the legs and abdomen due to fluid retention, persistent cough

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Epoprostenol SUN

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

Do not use Epoprostenol Sun after the expiry date which is stated on the label of the vial and on the carton after EXP. The expiry date is the last day of the month shown.

Do not freeze.

Store the vial in the outer carton to protect it from light.

The reconstituted solution must be diluted to the final concentration within the first hour after reconstitution (see Information for Healthcare Professionals).

For information on storage conditions after reconstitution and dilution of the medicine, see Information for Healthcare Professionals.

Do not use this medicine if you notice the presence of particles in the reconstituted solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Epoprostenol Sun

Epoprostenol SUN 0.5 mg, powder for solution for infusion:

• The active ingredient is epoprostenol (as epoprostenol sodium). Each vial contains 0.531 mg of epoprostenol sodium equivalent to 0.5 mg of epoprostenol. One ml of reconstituted solution contains 0.1 mg of epoprostenol (as epoprostenol sodium).

Epoprostenol SUN 1.5 mg, powder for solution for infusion:

• The active ingredient is epoprostenol (as epoprostenol sodium). Each vial contains 1.593 mg of epoprostenol sodium equivalent to 1.5 mg of epoprostenol. One ml of reconstituted solution contains 0.3 mg of epoprostenol (as epoprostenol sodium).

The other components are glycine, sucrose, and sodium hydroxide (for pH adjustment).

Appearance of Epoprostenol Sun and Container Content

White or off-white powder in a transparent glass vial with a rubber stopper and an aluminum press-on cap.

Each container holds a vial containing 0.5 mg of powder.

Each container holds a vial containing 1.5 mg of powder.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Local Representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

Tel: +34 93 342 78 90

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Germany Epoprostenol SUN

France Epoprostenol SUN

Italy Epoprostenolo SUN

Netherlands Epoprostenol SUN

Spain Epoprostenol SUN

United Kingdom (Northern Ireland) Epoprostenol

Date of last revision of this leaflet: October 2023

This information is intended solely for healthcare professionals:

Renal Dialysis

There is a container available for use in the treatment of renal dialysis:

• A vial of 0.5 mg of powder.

Reconstitution:

Remove approximately 5 ml of sterile water for injection or sodium chloride 0.9% injection solution with a sterile syringe, inject into the vial containing Epoprostenol SUN, and gently agitate until the powder is dissolved. The reconstituted solution must be inspected before proceeding with dilution. Its use is prohibited if it presents particles or discoloration. The disposal of the unused reconstituted solution will be carried out in accordance with local regulations.

Dilution:

The reconstituted solution must be diluted to the final concentration within the first hour of reconstitution. Subsequent dilution should be carried out with the same solvent used for the reconstitution of the sterile lyophilized powder.

When Epoprostenol SUN lyophilized powder is reconstituted with sterile water for injection or sodium chloride 0.9% injection solution, the final injection solution has a pH between 11.5 and 12.

Calculation of Infusion Rate:

The infusion rate can be calculated from the following formula:

Infusion rate (ml/min) = Dose (ng/kg/min) × body weight (kg) / Concentration of the solution (ng/ml)

Infusion rate (ml/h) = infusion rate (ml/min) × 60

Pulmonary Arterial Hypertension

There are two containers available for use in the treatment of pulmonary arterial hypertension:

• A vial of 0.5 mg of powder.
• A vial of 1.5 mg of powder.

Reconstitution:

Remove approximately 5 ml of sterile water for injection or sodium chloride 0.9% injection solution with a sterile syringe, inject into the vial containing Epoprostenol SUN, and gently agitate until the powder is dissolved. The reconstituted solution must be inspected before proceeding with dilution. Its use is prohibited if it presents particles or discoloration. The disposal of the unused reconstituted solution will be carried out in accordance with local regulations.

Dilution:

The reconstituted solution must be diluted to the final concentration within the first hour of reconstitution. Subsequent dilution should be carried out with the same solvent used for the reconstitution of the sterile lyophilized powder. When administered chronically, Epoprostenol SUN should be prepared in a suitable drug administration reservoir for the infusion pump.

When Epoprostenol SUN lyophilized powder is reconstituted with sterile water for injection or sodium chloride 0.9% injection solution, the final injection solution has a pH between 11.5 and 12.

Among the ambulatory pumps suitable for use in the administration of Epoprostenol SUN are:

• CADD-Legacy 1
• CADD-Legacy PLUS

Manufactured by Smiths Medical.

Among the pump accessories compatible with the administration of Epoprostenol SUN are:

• Disposable medication cassettes CADD 50 mL; 100 mL from Smiths Medical.
• Extension set with internal 0.2-micron filter (CADD extension set with male Luer, air-eliminating filter 0.2 microns, clamp, and integral anti-siphon valve with male Luer) from Smiths Medical.

Only extension sets with internal 0.22-micron filters should be used between the infusion pump and the catheter. It is recommended to use filters with a hydrophilic polyethersulfone membrane. The extension set and internal filter must be changed at least every 48 hours.

The diluted solution of Epoprostenol SUN (pH 12) should not be used with administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG).

The vial containing 0.5 mg of epoprostenol should be used for the preparation of solutions with concentrations less than 15,000 ng/mL.

Table 1 shows examples of the preparation of usual concentrations of Epoprostenol SUN solutions. Each vial is for single use only.

Table 1: Usual concentrations: examples of reconstitution and dilution

Epoprostenol SUN, diluted to the final concentration in the drug administration reservoir following the instructions, can be administered immediately at room temperature (25°C) or stored for a maximum of 8 days between 2 and 8°C according to the usage conditions described in Table 2.

Table 2: Maximum administration duration (hours) at room temperature (25°C) of fully diluted solutions stored in the drug administration reservoir.

Do not expose the fully diluted solution to direct sunlight.

Special precautions for storage

Do not freeze.

The reconstituted solution must be diluted to the final concentration within the first hour of reconstitution.

Reconstitution and dilution should be carried out immediately before use.

Freshly prepared diluted solutions of epoprostenol for the treatment of pulmonary arterial hypertension can be administered immediately at 25°C or stored in the drug administration reservoir to protect from light for a maximum of 8 days between 2 and 8°C according to the usage conditions described in Table 2.