Epoprostenol Normon 1.5 mg powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Epoprostenol NORMON 1.5 mg powder for solution for infusion

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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

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

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

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

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

Epoprostenol NORMON is used to prevent blood clotting during renal dialysis, in emergency situations when heparin cannot be used.

2. What you need to know before using Epoprostenol NORMON

Do not use Epoprostenol NORMON

• if you are allergic to epoprostenol or to any of the other ingredients of this medicine (listed in section 6),
• if you have heart failure,
• if you begin to develop fluid accumulation in your lungs causing difficulty in breathing after starting treatment.

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

Warnings and precautions

Inform your doctor before using Epoprostenol NORMON:

• if you have bleeding disorders,
• if you are on a low-sodium diet.

Skin injury at the injection site:

Epoprostenol NORMON is injected into a vein. It is important that the medicine does not leak or seep out of the vein into the surrounding tissues. If it does, it may damage the skin. Symptoms include:

• tenderness,
• burning,
• itching,
• swelling,
• redness.

This may progress to blister formation and skin peeling. It is important that you monitor the injection site while being treated with Epoprostenol NORMON.

Contact the hospital immediately if the injection site becomes painful, stings, swells, or if you notice any blistering or skin peeling.

Effect of Epoprostenol NORMON on blood pressure and heart rate:

Epoprostenol NORMON may increase or decrease your heart rate. Your blood pressure may also become very low. While being treated with Epoprostenol NORMON, your heart rate and blood pressure should be monitored. Symptoms of low blood pressure include dizziness and fainting.

Inform your doctor if you experience any of these symptoms. It may be necessary to reduce your dose or interrupt the infusion.

Use of Epoprostenol NORMON with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Some medicines may affect how Epoprostenol NORMON works, or may make it more likely that you experience side effects. Epoprostenol NORMON 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 known as NSAIDs),
• digoxin (used to treat heart disorders).

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine, as symptoms may worsen during pregnancy.

It is unknown whether the components of Epoprostenol NORMON pass into human milk. Breastfeeding must be discontinued while being treated with Epoprostenol NORMON.

Driving and using machines

This treatment may affect your ability to drive or operate machinery.

Do not drive or use machines unless you feel well.

Epoprostenol NORMON contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per vial and is therefore considered essentially “sodium-free”.

3. How to use Epoprostenol NORMON

Follow exactly the instructions given by your doctor or pharmacist for the administration of this medicine. If in doubt, consult your doctor or pharmacist again.

Your doctor will determine how much Epoprostenol NORMON is appropriate for you. The amount administered 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 NORMON is administered by slow infusion (drip) into a vein.

Pulmonary arterial hypertension

Your initial treatment will be given in a hospital. This is because your doctor needs to monitor you and identify the most suitable dose for you.

Treatment will begin with an infusion of Epoprostenol NORMON. The dose will be gradually increased until your symptoms are relieved and side effects are controlled. Once the optimal dose has been determined, a permanent catheter (venous access) will be placed in one of your veins. After this, you may be treated using an infusion pump.

Renal dialysis

You will receive an Epoprostenol NORMON infusion throughout the duration of your dialysis session.

Use of Epoprostenol NORMON 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 NORMON. They will also instruct you on how to stop the treatment if necessary. Discontinuation of Epoprostenol NORMON must be done gradually. It is important that you carefully follow all instructions.

Epoprostenol NORMON comes as a powder in a glass vial. Before use, the powder must be dissolved.

Catheter care

If a catheter has been placed in your vein, it is very important to keep this area clean, as otherwise it could become infected. Your doctor or nurse will teach you how to clean the catheter and the surrounding area. It is essential that you carefully follow all instructions.

If you use more Epoprostenol NORMON than you should

Seek urgent medical attention if you think you have used or been given too much Epoprostenol NORMON. In case of overdose or accidental injection, contact your doctor, nurse, or pharmacist immediately, or call the Toxicology Information Service at telephone number: 91 562 04 20, stating the name of the medicine and the amount injected. Symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, feeling of warmth or tingling, or feeling like you might faint (dizziness/vertigo).

If you forget to use Epoprostenol NORMON

Do not use a double dose to make up for a missed dose.

If you stop using Epoprostenol NORMON

Stopping Epoprostenol NORMON treatment must be done gradually. If you stop treatment too quickly, you may experience serious adverse effects, including dizziness, weakness, and difficulty breathing. If you have problems with the infusion pump or catheter, such as a stoppage preventing Epoprostenol NORMON administration, contact your doctor, nurse, or hospital immediately.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

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

• You feel your heart beating faster, or have chest pain or difficulty breathing.
• You feel dizzy or faint, especially when standing up.
• You have fever or chills.
• You bleed more often, or for longer periods.

Very common adverse effects

These may affect more than 1 in 10 people:

• headache,
• jaw pain,
• non-specific pain,
• vomiting,
• nausea,
• diarrhoea,
• redness of the face (facial flushing)

Common adverse effects

These may affect up to 1 in 10 people:

• blood infection (septicaemia),
• rapid heartbeat,
• slow heartbeat,
• low blood pressure,
• bleeding in various locations and increased tendency to bruising, for example nosebleeds or bleeding gums,
• stomach discomfort or stomach pain,
• chest pain,
• joint pain,
• feeling anxious, feeling nervous,
• skin rash,
• pain at the injection site

Common adverse effects that may appear in your blood tests

• decrease in the number of platelets in the blood (cells that help blood clotting).

Uncommon adverse effects

These may affect up to 1 in 100 people:

• sweating,
• dry mouth

Rare adverse effects

These may affect up to 1 in 1,000 people:

• infection at the injection site

Very rare adverse effects

These may affect up to 1 in 10,000 people:

• feeling of tightness around the chest,
• tiredness, weakness,
• restlessness,
• paleness,
• redness at the injection site,
• overactive thyroid glands,
• blockage of the intravenous catheter

Other adverse effects

The frequency is unknown (cannot be estimated from the available data):

• enlarged or overactive spleen,
• fluid accumulation in the lungs (pulmonary oedema),
• increased blood sugar (glucose) levels,
• swelling due to fluid accumulation around the stomach,
• excessive pumping of blood from the heart leading to shortness of breath, fatigue, swelling of the legs and abdomen due to fluid accumulation, persistent cough.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Epoprostenol NORMON

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

Do not use this medicine after the expiry date stated on the container after “EXP”. The expiry date refers to the last day of the month indicated.

Do not store above 25°C. Store in the original packaging to protect from light and moisture. Do not freeze.

Use after storage of the reconstituted solution:

Prior to use, reconstituted Epoprostenol NORMON solutions prepared with 5 ml of water for injection or 0.9% sodium chloride should be protected from light and are chemically stable for 5 days if stored refrigerated at 2–8°C or up to 48 hours if stored at 25°C. Do not freeze reconstituted Epoprostenol NORMON solutions; discard any reconstituted solution that has been frozen. Likewise, discard any reconstituted solution that has been refrigerated for more than 5 days or kept at 25°C for longer than 48 hours.

Prior to administration, reconstituted Epoprostenol NORMON solutions must be further diluted to the final concentration using the same diluent used for reconstitution. During use, a diluted Epoprostenol NORMON solution of 15,000 ng/ml or higher concentration may be administered for up to 24 hours at room temperature (if lower concentrations are used, the pump reservoir must be changed every 12 hours when administered at room temperature). These solutions must be protected from light.

From a microbiological standpoint: The product should be used immediately. If not used immediately, the duration and conditions of in-use storage are the responsibility of the user and should not exceed 24 hours at 2–8°C, unless reconstitution was carried out under controlled and validated aseptic conditions.

Use after reconstitution and immediate dilution to final concentration:

Reconstituted Epoprostenol NORMON with 5 ml of water for injection or 0.9% sodium chloride, immediately diluted to final concentration in the drug administration reservoir, may be administered under the use conditions specified in the following table:

These solutions must be protected from light.

Disposal of unused medication and of all materials that have come into contact with it should be carried out in accordance with local regulations.

6. Package contents and other information

Composition of Epoprostenol NORMON

The active substance is epoprostenol. Each vial contains 1.5 mg of epoprostenol (as sodium epoprostenol).

The other components are: mannitol, arginine, and sodium hydroxide (for pH adjustment).

Appearance of the medicinal product and contents of the pack

Epoprostenol NORMON is presented as a powder for solution for infusion. Each package contains one vial of lyophilized powder.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.
Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of the most recent review of this leaflet: February 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicinal Products and Health Products: http://www.aemps.gob.es

This information is intended for healthcare professionals only:

Renal dialysis

Reconstituted epoprostenol solution (pH 11.5–13.5) must not be used with any preparation or administration material containing polyethylene terephthalate (PET) or glycol-modified polyethylene terephthalate (PETG). Based on published literature, the following preparation and administration materials are considered likely to be compatible:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Polyamide
• Polyethersulfone
• Polyethylene
• Polyisoprene
• Polyolefin
• Polypropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Polyvinyl chloride (PVC) (plasticized with bis(2-ethylhexyl) phthalate (DEHP))
• Polyvinylidene fluoride (PVDF)
• Silicone

Reconstitution:

Using a sterile syringe, inject 5 ml of water for injection or 0.9% sodium chloride into the vial containing 1.5 mg of lyophilized Epoprostenol NORMON and gently shake until the powder is completely dissolved. This solution is now referred to as the concentrated solution and contains 300,000 ng per ml of epoprostenol. Only this concentrated solution is suitable for further dilution prior to use.

Dilution:

To obtain a solution with an epoprostenol concentration of 30,000 ng per ml: Withdraw the concentrated solution using a syringe and add it to a sufficient volume of the same diluent to achieve a total final volume of 50 ml. Mix thoroughly.

To obtain a solution with an epoprostenol concentration of 5,000 ng per ml: Withdraw the concentrated solution using a syringe and add it to a sufficient volume of the same diluent to achieve a total final volume of 300 ml. Mix thoroughly.

If reconstituted and diluted as described above, epoprostenol infusion solutions will retain 90% of their initial potency.

Infusion rate calculation:

The infusion rate can be calculated using the following formula:

dose (ng/kg/min) × body weight (kg)
Infusion rate (ml/min) = -----------------------------------------------------
concentration of solution (ng/ml)

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

Pulmonary arterial hypertension

Reconstituted epoprostenol solution (pH 11.5–13.5) must not be used with any preparation or administration material containing polyethylene terephthalate (PET) or glycol-modified polyethylene terephthalate (PETG). Based on available data from published literature, the following preparation and administration materials are compatible:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Polyamide
• Polyethersulfone
• Polyethylene
• Polyisoprene
• Polyolefin
• Polypropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Polyvinyl chloride (PVC) (plasticized with bis(2-ethylhexyl) phthalate (DEHP))
• Polyvinylidene fluoride (PVDF)
• Silicone

Suitable ambulatory pumps for use include:

• CADD-Legacy 1
• CADD-Legacy PLUS
• CADD-Solis VIP (variable infusion profile)

Manufactured by Smiths Medical.

Compatible pump accessories include:

• CADD medication cassette “reservoir” 50 ml and 100 ml from Smiths Medical.
• CADD extension set with in-line 0.2-micron filter (CADD extension set with male luer; 0.2-micron air-elimination filter, clamp, and integral anti-siphon valve with male luer) from Smiths Medical.

The extension set and in-line filter must be changed at least every 48 hours.

Reconstitution:

Reconstitution shall be performed according to the instructions described for renal dialysis.

Dilution:

The concentrated solution must be diluted for use in the treatment of pulmonary arterial hypertension.

The concentrations commonly used in the treatment of pulmonary arterial hypertension are as follows:

• 30,000 ng/ml: 1.5 mg of epoprostenol reconstituted with 5 ml of water for injection or 0.9% sodium chloride and diluted to a total volume of 50 ml with the same diluent.
• 15,000 ng/ml: 1.5 mg of epoprostenol reconstituted with 5 ml of water for injection or 0.9% sodium chloride and diluted to a total volume of 100 ml with the same diluent.

The maximum recommended concentration for administration in primary or secondary pulmonary hypertension is 60,000 ng/ml.

Epoprostenol NORMON must not be administered with other solutions or parenteral medicinal products when used for pulmonary arterial hypertension.

To dilute the concentrated solution, transfer it into a syringe and dispense it directly into the pump cassette. Then, add the required volume of diluent to the concentrated Epoprostenol NORMON solution in the cassette. Mix well.

The portable pump used to administer Epoprostenol NORMON 1.5 mg must: (1) be small and lightweight, (2) allow adjustment of infusion rates in increments of nanograms/kg/min, (3) have alarms for occlusion, end of infusion, and low battery, (4) provide an accuracy of ±6% of the programmed rate, (5) operate with positive pressures (continuous or pulsatile), with pulse intervals not exceeding 3 minutes at the infusion rates used for administering Epoprostenol NORMON 1.5 mg. The reservoir must be made of polypropylene or glass.

Protect infusion bags from light during infusion.

Infusion rate calculation:

The infusion rate can be calculated using the formula described above for renal dialysis. In long-term administration of Epoprostenol NORMON, higher infusion rates may be required, and therefore more concentrated solutions may be needed.