Veletri 0.5 mg powder and solvent for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

VELETRI 0.5 mg powder and solvent for solution for infusion

VELETRI 1.5 mg powder and solvent for solution for infusion

epoprostenol

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as 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 could harm them.

  • If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What VELETRI is and what it is used for

2. What you need to know before you start using VELETRI

3. How to use VELETRI

4. Possible side effects

   1. Storage of VELETRI

5. Contents of the pack and other information

1. What VELETRI is and what it is used for

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

VELETRI 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. VELETRI widens the blood vessels to reduce blood pressure in the lungs.

VELETRI is used to prevent blood clotting during renal dialysis when heparin cannot be used.

2. What you need to know before you start using VELETRI

Do not use VELETRI

• if you are allergic to VELETRI 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 the lungs causing difficulty in breathing after starting treatment.

If you think you are in any of these situations, do not use VELETRI until you have consulted your doctor.

Warnings and precautions

Talk to your doctor before starting to use VELETRI.

Before you are given VELETRI, your doctor needs to know:

• if you have problems with bleeding.

Skin injuries at the injection site

VELETRI is injected into a vein. It is important that the medicine does not leak or infiltrate from the vein into the surrounding tissues. If it does, skin damage may occur. Symptoms include:

• tenderness
• burning
• stinging
• swelling
• redness.

This may progress to blister formation and skin peeling. It is important to monitor the injection site while receiving treatment with VELETRI.

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

Effect of VELETRI on blood pressure and heart rate

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

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

Children and adolescents

The safety and efficacy of VELETRI in children have not yet been established.

Other medicines and VELETRI

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 VELETRI works, or may make it more likely that you experience side effects. VELETRI 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 conditions).

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

Pregnancy and breastfeeding

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

It is unknown whether the components of VELETRI pass into breast milk. You must stop breastfeeding while being treated with VELETRI.

Driving and using machines

This treatment may affect your ability to drive and use machines.

Do not drive or operate machinery unless you feel well.

VELETRI contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; essentially, it is “sodium-free”.

3. How to use VELETRI

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

VELETRI is supplied as a powder in a small glass vial. The powder must be dissolved before use.

VELETRI must not be administered by rapid intravenous injection. It must always be administered by intravenous infusion.

Your doctor will decide the appropriate dose of VELETRI for you. The dose you receive is based on your body weight and the type of condition you have. Your dose may be increased or decreased depending on how well you respond to treatment.

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

Pulmonary arterial hypertension

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

Treatment will start with an infusion of VELETRI. The dose will be gradually increased until your symptoms are relieved and side effects are controlled. Once the optimal dose has been identified, a permanent catheter (venous access) will be placed in one of your veins. Then, treatment can be continued using an infusion pump.

Renal dialysis

You will receive a VELETRI infusion during dialysis.

Use of VELETRI at home (only for the treatment of Pulmonary Arterial Hypertension)

If you are receiving treatment at home, your doctor or nurse will teach you how to prepare and use VELETRI. They will also instruct you on how to stop treatment if necessary. Discontinuation of VELETRI must be done gradually. It is very important that you carefully follow all instructions.

VELETRI is supplied as a powder in a glass vial. The powder must be dissolved in a liquid before use. The liquid does not contain preservatives. Any unused liquid must be discarded.

Catheter care

If a catheter has been placed in your vein, it is very important to keep this area clean; otherwise, it could become infected. Your doctor or nurse will teach you how to clean the catheter and the area around it. It is very important that you carefully follow all instructions. It is also very important that you strictly follow all instructions regarding changing the drug delivery system of the pump (cassette), and that you always use an infusion set with an in-line filter, as instructed by your doctor, to reduce the risk of infection. When reconnecting your infusion set, always make sure to clear any excess drops so that no liquid remains in the outer space between the infusion set and the catheter connectors, as this may damage the materials.

If you use more VELETRI than you should

Seek urgent medical attention if you think you have used or been given too much VELETRI. Symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, warmth or tingling, or feeling like you might faint (dizziness/vertigo).

If you forget to use VELETRI

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

If you stop using VELETRI

Discontinuation of VELETRI must be done gradually. If treatment is stopped too quickly, you may experience serious adverse effects, including dizziness, feeling weak, and difficulty breathing. If you have problems with the infusion pump or catheter, such as it stops or prevents treatment with VELETRI, 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 can cause adverse effects, although not everyone will experience them.

Very common adverse effects

May affect more than 1 in 10 people:

• headache
• jaw pain
• pain
• feeling sick (nausea)
• vomiting
• diarrhea
• redness of the face (facial flushing)

Common adverse effects

May affect up to 1 in 10 people:

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

Common adverse effects that may appear in blood tests

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

Uncommon adverse effects

May affect up to 1 in 100 people:

• sweating
• dry mouth

Rare adverse effects

May affect up to 1 in 1,000 people:

• infection at the injection site

Very rare adverse effects

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
• intravenous catheter blockage

Other adverse effects

Frequency unknown:

• increase in size or activity of the spleen

• fluid accumulation in the lungs (pulmonary edema)

• increased levels of sugar (glucose) in the blood

• ascites (accumulation of fluid in the abdomen)

• excessive pumping of blood from the heart leading to difficulty breathing, fatigue, swelling of the legs and abdomen due to fluid accumulation, persistent cough

• hives (urticaria)

Reporting of adverse effects

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

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

If you experience any adverse effect, talk to 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: Website: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of VELETRI

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

Do not use this medicine after the expiry date stated on the carton, vial of powder and vial of solvent, after EXP. The expiry date refers to the last day of the month indicated.

Do not freeze.

The solvent does not contain preservatives; therefore, each vial must be used only once and then discarded.

The reconstituted solution must be immediately diluted to the final concentration (see Information for Healthcare Professionals).

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

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

Medicines should not be disposed of via wastewater or household waste. If you are unsure how to dispose of unused or expired containers and medicines, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of VELETRI

VELETRI 0.5 mg powder and solvent for solution for infusion

• The active substance 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).

VELETRI 1.5 mg powder and solvent for solution for infusion

• The active substance 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 Sucrose, Arginine, and Sodium Hydroxide (for pH adjustment).

Solvent:

Each solvent vial contains 100 mL of Water for Injections.

Nature of the product and pack contents

White or almost white powder in a clear glass vial with a rubber stopper and aluminum seal.

Each pack contains one vial of 0.5 mg powder.

Each pack contains one vial of 1.5 mg powder.

Each pack contains one 100 mL bottle of solvent. The solvent is a clear, colourless solution.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Janssen‑Cilag International NV
Turnhoutseweg 30
B‑2340 Beerse
Belgium

Manufacturer:

Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Janssen-Cilag, S.A.
Paseo del Club Deportivo 1, Edificio 16
28223 Pozuelo de Alarcón (Madrid)
Spain

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

Belgium, Czech Republic, France, Germany, Greece, Hungary, Ireland, Luxembourg, Netherlands, Poland, Portugal, Slovakia, Spain, United Kingdom (Northern Ireland): VELETRI

Italy: CARIPUL

Date of most recent review of this leaflet: July 2025.

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This information is intended for healthcare professionals only:

INFORMATION FOR HEALTHCARE PROFESSIONALS

Renal dialysis

Two pack sizes are available for use in renal dialysis treatment:

• 1 vial containing sterile lyophilized VELETRI, equivalent to 0.5 mg of VELETRI, supplied with a 100 mL bottle of solvent.
• 1 vial containing sterile lyophilized VELETRI, equivalent to 0.5 mg of VELETRI, supplied without solvent.

Reconstitution:

Withdraw 5 mL of the solvent into a sterile syringe, inject the syringe contents into the vial containing VELETRI, and gently shake until the powder is completely dissolved. The reconstituted solution should be inspected before proceeding to dilution. Do not use if particulate matter is present or if there is any discoloration. Any unused reconstituted solution must be disposed of in accordance with local regulations.

Dilution:

The reconstituted solution must be diluted immediately to the final concentration. Any further dilution must be performed using the same solvent used for reconstitution of the sterile lyophilized powder.

Infusion rate calculation:

The infusion rate can be calculated using 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

Four pack sizes are available for use in the treatment of pulmonary arterial hypertension:

• 1 vial containing sterile lyophilized VELETRI, equivalent to 0.5 mg of VELETRI supplied with a 100 ml solvent vial.
• 1 vial containing sterile lyophilized VELETRI, equivalent to 1.5 mg of VELETRI supplied with a 100 ml solvent vial.
• 1 vial containing sterile lyophilized VELETRI, equivalent to 0.5 mg of VELETRI supplied alone.
• 1 vial containing sterile lyophilized VELETRI, equivalent to 1.5 mg of VELETRI supplied alone.

Initially, the pack containing the parenteral solvent should be used. During chronic treatment with VELETRI, the final concentration of the solution may be increased by adding another 0.5 mg or 1.5 mg vial of lyophilized VELETRI.

Reconstitution:

Withdraw 5 ml of diluent into a sterile syringe, inject the syringe contents into the vial containing VELETRI, and gently shake until the powder is completely dissolved. The reconstituted solution should be inspected before proceeding to dilution. Do not use if particulate matter or discoloration is present. Any unused reconstituted solution must be discarded according to local regulations.

Dilution:

The reconstituted solution must be immediately diluted to the final concentration. Any further dilution must be performed using the same diluent used for reconstitution of the sterile lyophilized powder.

When VELETRI is administered chronically, it must be prepared in an appropriate drug delivery reservoir compatible with the infusion pump.

Suitable ambulatory pumps for use in the administration of VELETRI include:

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

Manufactured by Smiths Medical.

Compatible pump accessories for the administration of VELETRI include:

• Smiths Medical Medication CADD Cassettes (disposable 50 ml and 100 ml reservoirs)
• CADD infusion set with in-line 0.2 micron filter (CADD extension set with male luer, air elimination 0.2 micron filter, clamp, and integral anti-siphon valve with male luer) from Smiths Medical.

Based on available internal testing data and manufacturer instructions for use of the accessories, the following materials are considered possibly compatible for preparation and administration:

• Acrylics
• Acrylonitrile butadiene styrene (ABS)
• Polycarbonate
• Polyethersulfone
• Polypropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Polyvinyl chloride (PVC) (plasticized with DEHP)
• Silicone

It is unknown whether polyethylene terephthalate (PET) and polyethylene glycol terephthalate (PETG) are compatible with VELETRI, as these materials have not been tested with VELETRI; therefore, their use is not recommended.

Only infusion sets with an in-line 0.22 micron filter placed between the infusion pump and the catheter should be used. Hydrophilic polyethersulfone membrane filters are recommended. The infusion set and in-line filter must be changed at least every 48 hours.

The vial containing 0.5 mg of epoprostenol should be used for the preparation of solutions with final concentrations below 15,000 ng/ml.

Table 1 provides examples for the preparation of commonly used concentrations of VELETRI solutions. Each vial is for single use only.

Table 1: Frequently Used Concentrations – Examples of Reconstitution and Dilution
Final concentration (ng/mL)	Instructions:
3,000 ng/mL	Dissolve the contents of a 0.5 mg vial with 5 mL of solvent. Withdraw 3 mL from the vial and dilute to a final volume of 100 mL with the same diluent.
5,000 ng/mL	Dissolve the contents of a 0.5 mg vial with 5 mL of solvent. Withdraw all the contents of the vial and dilute to a final volume of 100 mL with the same diluent.
10,000 ng/mL	Dissolve the contents of two 0.5 mg vials with 5 mL of solvent each. Withdraw all the contents from the vials and dilute to a final volume of 100 mL with the same diluent.
15,000 ng/mL*	Dissolve the contents of a 1.5 mg vial with 5 mL of solvent. Withdraw all the contents of the vial and add to a sufficient volume of the same diluent to achieve a final volume of 100 mL.
30,000 ng/mL*	Dissolve the contents of two 1.5 mg vials with 5 mL of solvent each. Withdraw all the contents from the vials and dilute to a final volume of 100 mL with the same diluent.
30,000 ng/mL*	Dissolve the contents of a 1.5 mg vial with 5 mL of solvent. Withdraw all the contents of the vial and dilute to a final volume of 50 mL with the same diluent.
Higher final concentrations may be required when administering VELETRI for long-term therapy

Diluted VELETRI to the final concentration in the drug delivery reservoir as indicated can be administered immediately at room temperature (25 °C) or, if stored, for up to 8 days at a temperature of 2 °C to 8 °C, under the conditions of use specified in Table 2.

Table 2: Maximum Duration of Administration (hours) at Room Temperature (25°C) for Fully Diluted Solutions Stored in the Drug Administration Reservoir
Final Concentration Range	Immediate Administration	If Stored for up to 8 Days at 2°C to 8°C
> 3,000 ng/mL and < 15,000 ng/mL	48 hours	24 hours
> 15,000 ng/mL	48 hours	48 hours

Do not expose the fully diluted solution to direct sunlight.

Special storage precautions

Do not freeze.

The reconstituted solution must be immediately diluted to the final concentration.

Reconstitution and dilution must be performed immediately before administration.

Freshly prepared diluted solutions of epoprostenol for the treatment of pulmonary arterial hypertension can be administered immediately at 25°C, or may be stored in the drug delivery reservoir protected from light for up to 8 days at a temperature of 2°C to 8°C, under the use conditions indicated in Table 2.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.es/