Prospect: information for theuser

Epoprostenol NORMON 1.5 mg powder for solution for infusion

Read this prospect carefully before starting tousethis medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor,pharmacist or nurse.
• This medication has been prescribed to you alone, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

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

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

Do not use Epoprostenol NORMON

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

If you consider that 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 problems.
• if you are on a low-sodium diet.

Skin lesion at the injection site:

Epoprostenol NORMON is injected into a vein. It is essential that the medication does not leak or filter out of the vein into the surrounding tissues. If it does, it will damage the skin. The symptoms are:

• sensitivity,
• burning,
• itching,
• swelling,
• redness.

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

Contact the hospital immediately if the injection site becomes painful, itches, or becomes inflamed or if you notice any blister formation or skin peeling.

Effect of Epoprostenol NORMON on blood pressure and heart rate:

Epoprostenol NORMON may accelerate or slow down 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 discontinue infusion.

Use of Epoprostenol NORMON with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription.

Some medications may affect the functioning of Epoprostenol NORMON, or make it more likely that you will experience adverse effects. Epoprostenol NORMON may also affect the functioning of other medications if taken at the same time. These include:

• medications used to treat high blood pressure,
• medications used to prevent blood clot formation,
• medications used to dissolve blood clots,
• medications used to treat inflammation or pain (also known as NSAIDs),
• digoxin (used to treat heart disorders).

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

Pregnancy, breastfeeding, and fertility

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

The components of Epoprostenol NORMON are unknown to pass into human milk. You should discontinue breastfeeding while being treated with Epoprostenol NORMON.

Driving and operating machinery

The treatment may affect your ability to drive and operate machinery.

Do not drive or operate machinery unless you feel well.

Epoprostenol NORMON contains sodium

This medication contains less than 23 mg (1 mmol) of sodium per vial, making it essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will tell you how much Epoprostenol NORMON is suitable for you. The amount you are 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 through slow infusion (drip) in a vein.

Pulmonary arterial hypertension

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

Start with a infusion of Epoprostenol NORMON. The dose will be increased until your symptoms improve and side effects are controlled. Once the best dose is identified, a permanent catheter (line) will be placed in one of your veins. You will then be treated with a pump for infusion.

Renal dialysis

You will be administered an infusion of Epoprostenol NORMON during the duration of your dialysis.

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 tell you how to interrupt treatment if necessary. Discontinuation of Epoprostenol NORMON should be done gradually. It is essential that you carefully follow all instructions.

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

Care of the catheter

If a catheter has been placed in a vein, it is very important to keep this area clean, or it could become infected. Your doctor or nurse will teach you how to clean the catheter and the area around it. 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 administered too much Epoprostenol NORMON. In case of overdose or accidental injection, consult your doctor, nurse, or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount injected.The symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, heat or tingling, or a sensation of dizziness or vertigo.

If you forgot to use Epoprostenol NORMON

Do not use a double dose to compensate for the missed doses.

If you interrupt treatment with Epoprostenol NORMON

Discontinuation of Epoprostenol NORMON should be done gradually. If you interrupt treatment too quickly, you may experience severe 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 NORMON, contact your doctor, nurse, or hospital immediately.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

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

Very common side effects

These may affect more than 1 in 10 people:

• headache,
• jaw pain,
• unspecified pain,
• vomiting,
• nausea,
• diarrhea,
• flushing of the face (facial flushing)

Common side effects

These may affect up to 1 in 10 people:

• blood infection (septicemia),
• rapid heartbeats,
• slow heartbeats,
• low blood pressure,
• bleeding in various locations and increased ease of bruising, for example, nosebleeds or gum bleeding,
• uncomfortable or stomach pain,
• chest pain,
• joint pain,
• sensation of anxiety, sensation of nervousness,
• skin rash,
• pain at the injection site

Common side effects that may appear in your blood tests

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

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:

• sensation of chest tightness,
• fatigue, weakness,
• agitation,
• pallor,
• flushing at the injection site,
• hyperactive thyroid glands,
• occlusion of the intravenous catheter

Other side effects

We do not know how many people are affected:

• enlarged or hyperactive spleen,
• accumulation of fluid in the lungs (pulmonary edema),
• increase in blood sugar (glucose)
• swelling due to the accumulation of fluid around the stomach
• excessive pumping of blood from the heart that leads to difficulty breathing, fatigue, swelling of the legs and abdomen due to fluid accumulation, persistent cough.

Reporting of side effects:

If you experience any type of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after “CAD.” The expiration date is the last day of the month indicated.

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

Use after storage of the reconstituted solution:

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

Before administration, reconstituted solutions of Epoprostenol NORMON must be further diluted to the final concentration with the same diluent used for reconstitution. During use, a diluted solution of Epoprostenol NORMON of 15,000 ng/ml or higher concentration can be administered for a period of 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 point of view:The product must be used immediately. In case it is not used immediately, the times and conditions of storage in use are the responsibility of the user and should not be extended beyond 24 hours at 2 to 8°C, unless reconstitution was carried out in controlled and validated aseptic conditions.

Use after reconstitution and immediate dilution to the final concentration:

Epoprostenol NORMON reconstituted with 5 ml of injection water or sodium chloride 0.9% and immediately diluted to the final concentration in the medication administration reservoir can be administered according to the conditions of use indicated in the table below:

These solutions must be protected from light.

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

Composition of Epoprostenol NORMON

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

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

Appearance of the product and contents of the package

Epoprostenol NORMON is presented in the form of a powder for solution for infusion. Each package contains a vial of lyophilized powder.

Holder of the marketing authorization and responsible for manufacturing

Laboratorios NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Last review date of this leaflet: February 2023

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Deviceshttp://www.aemps.gob.es

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This information is intended solely for healthcare professionals:

Renal dialysis

The epoprostenol solution reconstituted with solvent (pH 11.5-13.5) should not be used with any preparation or administration material containing polyethylene terephthalate (PET) or polyethylene terephthalate modified with glycol (PETG). Based on published literature, compatible preparation and administration materials likely include:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Nylon
• Polysulfone
• Polyethylene
• Isoprene
• Polyolefin
• Polpropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Chlorinated polyvinyl chloride (PVC) (plasticized with bis(2-ethylhexyl) phthalate (DEHP)
• Fluorinated polyvinylidene (PVDF)
• Silicone

Reconstitution:

Inject with a sterile syringe 5 ml of injection water or sodium chloride 0.9% into the vial containing 1.5 mg of lyophilized Epoprostenol NORMON and gently agitate until the powder has dissolved. This solution is now called the concentrated solution and contains 300,000 ng per ml of epoprostenol. Only this concentrated solution is suitable for subsequent dilutions before use.

Dilution:

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

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

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

Calculation of infusion rate:

The infusion rate can be calculated from the following formula:

dose (ng/kg/min) x body weight (kg)

Infusion rate (ml/min) = -----------------------------------------------------

concentration of the solution (ng/ml)

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

Pulmonary arterial hypertension

The epoprostenol solution reconstituted with solvent (pH 11.5-13.5) should not be used with any preparation or administration material containing polyethylene terephthalate (PET) or polyethylene terephthalate modified with glycol (PETG). Based on available literature data, compatible preparation and administration materials include:

• Modified acrylic
• Acrylonitrile butadiene styrene (ABS)
• Cyclic olefin polymer
• Nylon
• Polysulfone
• Polyethylene
• Isoprene
• Polyolefin
• Polpropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Chlorinated polyvinyl chloride (PVC) (plasticized with bis(2-ethylhexyl) phthalate (DEHP)
• Fluorinated polyvinylidene (PVDF)
• Silicone

Compatible ambulatory pumps for use include:

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

Manufactured by Smiths Medical.

Compatible accessories for the pumps include:

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

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

Reconstitution:

Will be carried out in accordance with the instructions described for renal dialysis.

Dilution:

The concentrated solution must be diluted to be used in the treatment of pulmonary arterial hypertension.

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

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

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

Epoprostenol NORMON should not be administered with other solutions or parenteral medications when administered in pulmonary arterial hypertension

To dilute the concentrated solution, pass it to a syringe and dispense it directly into the pump cassette. Then, dispense the additional diluent into the Epoprostenol NORMON concentrated solution in the cassette. Mix well.

The portable pump used to administer Epoprostenol NORMON 1.5 mg must (1) be small and light, (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) start with positive pressures (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at the infusion rates used to administer Epoprostenol NORMON 1.5 mg. The reservoir must be made of polpropylene or glass.

Protect the infusion bags from light during infusion.

Calculation of infusion rate:

The infusion rate can be calculated from 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.