Label: 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 this label carefully before starting to use this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.

-This medicine has been prescribed only for you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

1.What is VELETRI and how it is used

2.What you need to know before starting to use VELETRI

3.How to use VELETRI

4.Adverse effects

1. Storage of VELETRI
2. Contents of the package and additional information

VELETRI contains the active ingredient epoprostenol, which belongs to a group of medications called prostaglandins that prevent blood from clotting and dilate blood vessels.

VELETRI is used to treat a lung disease known as «pulmonary arterial hypertension». This occurs when the pressure in the blood vessels of the lungs is high. VELETRI dilates the blood vessels to reduce blood pressure in the lungs.

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

Do not use VELETRI

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

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

Warnings and precautions

Consult your doctor before starting to use VELETRI.

Your doctor needs to know:

• if you havebleeding problems.

Lesions on the skin at the injection site

VELETRI is injected into a vein. It is essential that the medicine does not leak or filter out of the vein into the surrounding tissues. If it does, the skin may be damaged. The symptoms are:

• sensitivity
• burning
• tingling
• swelling
• redness.

This may continue with the formation of blisters and skin peeling. It is essential that you check the injection site while receiving treatment with VELETRI.

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

Effect of VELETRI on blood pressure and heart rate

VELETRI may speed up or slow down the heartbeat. 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 includedizzinessandsyncope.

Inform your doctorif you have 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 been established yet.

Other medicines and VELETRI

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

Some medicines may affect the way VELETRI works, or make it more likely that you will experience adverse effects. VELETRI may also affect the way other medicines work if taken at the same time. These medicines include:

• medicines used totreat high blood pressure
• medicines used toprevent blood clot formation
• medicines used todissolve blood clots
• medicines used to treatinflammation or pain(also known as NSAIDs)
• digoxin (used to treatheart diseases).

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

Pregnancy and breastfeeding

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

It is unknownwhether the components of VELETRI can pass into breast milk.You should stop breastfeeding while being treated with VELETRI.

Driving and operating machinery

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

Do not drive or operate machineryunless you feel well.

VELETRI contains sodium

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

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

VELETRI is presented in the form of powder in a small glass vial. The powder must be dissolved before use.

VELETRI should not be administered by rapid injection into a vein. It must always be administered by intravenous infusion.

Your doctor will decide what amount of VELETRI is suitable for you. The amount you receive is based on your body weight and the type of disease you have. It is possible that your dose will 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

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.

You will start with a VELETRI infusion. The dose will be increased, until your symptoms improve, and side effects are controlled. Once the best dose has been identified, a permanent catheter (line) will be placed in one of your veins. Then, you will be able to be treated using a pump infusion system.

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 interrupt treatment if necessary. Stopping VELETRI should be done gradually. It is very important that you carefully follow all instructions.

VELETRI is presented in the form of powder in a glass vial. The powder must be dissolved in a liquid before use.The liquid does not contain preservatives. You should discard any unused liquid.

Care of the Catheter

If a catheter has been placed in a vein, it isvery importantto keep this area clean; if not, 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 alsovery importantthat you carefully follow all instructions regarding the change of the medication delivery system from the pump (cassette) and that you always use an infusion system with an in-line filter, as instructed by your doctor,to reduce the risk of infection.When reconnecting your infusion system, make sure toclean any remaining dropsso that there is no liquid in the external space between the infusion system and the catheter connectors, as this can damage the materials.

If you use more VELETRI than you should

Seek urgent medical attentionif you think you have used or have been given too much VELETRI. Symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, heat or tingling sensation, or feeling like you may faint (dizziness).

If you forget to use VELETRI

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

If you interrupt treatment with VELETRI

Stopping VELETRI should be done gradually. If treatment is stopped too quickly, you may experience severe side effects, including dizziness, feeling weak, and difficulty breathing. If you have problems with the infusion pump or catheter, because it stops or prevents treatment with VELETRI,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 medicinemay cause side effects, although not everyone will experience them.

Very common side effects

May affectmore than 1 in 10people:

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

Common side effects

May affectup to 1 in 10people:

• blood infection (septicemia)
• rapid heartbeat
• slow heartbeat
• low blood pressure
• bleeding in various locations and increased tendency to bruise, 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 blood tests

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

Uncommon side effects

May affectup to 1 in 100people:

• sweating
• dry mouth

Rare side effects

May affectup to 1 in 1,000people:

• infection at the injection site

Very rare side effects

May affectup to 1 in 10,000people:

• sensation of pressure around the chest
• fatigue, weakness
• agitation
• pallor
• redness at the injection site
• hyperactive thyroid glands
• occlusion of the intravenous catheter

Other side effects

The frequency of these side effects is unknown:

• enlargement or increased activity of the spleen

• accumulation of fluid in the lungs (pulmonary edema)

• increase in blood sugar levels
• ascites (accumulation of fluid in the abdomen)
• excessive blood pumping from the heart leading to difficulty breathing, fatigue, swelling of the legs and abdomen due to fluid accumulation, persistent cough

Reporting side effects

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.

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 leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use, Website: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 sight and reach of children.

Do not use this medication after the expiration date that appears on the vial of powder and solvent vial, after CAD. The expiration date is the last day of the month indicated.

This medication (powder for infusion solution/powder and solvent for infusion solution) does not require any special storage temperature. 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 section 7).

For storage conditions after reconstitution and dilution of the medication see section 7.

Do not use this medication if you observe any particles in the reconstituted solution.

Medicines should not be thrown away through drains or in the trash. If in doubt, ask your pharmacist how to dispose of the containers and medications that you do not need.This will help protect the environment.

Composition of VELETRI

VELETRI 0.5 mg powder and diluent for solution for infusion

•The active ingredient is epoprostenol (as epoprostenol sodium).

Cada vial contains 0.531mg of epoprostenol sodium equivalent to 0.5mg of epoprostenol

One ml of reconstituted solution contains 0.1mg of epoprostenol (as epoprostenol sodium).

VELETRI 1.5 mg powder and diluent for solution for infusion

• The active ingredient is epoprostenol (as epoprostenol sodium).

Cada vial contains 1.593mg of epoprostenol sodium equivalent to 1.5mg of epoprostenol.

One ml of reconstituted solution contains 0.3mg of epoprostenol (as epoprostenol sodium).

• The other components are Sucrose, Arginine and Sodium Hydroxide (for pH adjustment).

Diluent:

Cada vial of diluent contains 100ml of water for injection.

Appearance of the product and contents of the pack

White or off-white powder in a transparent glass vial with a rubber stopper and aluminum seal.

Each pack contains one vial of 0.5mg powder.

Each pack contains one vial of 1.5mg powder.

Each pack contains one bottle of 100ml of diluent. The diluent is a transparent and 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 about this medicinal product, please contact the local representative of the marketing authorisation holder:

Janssen-Cilag, S.A.

Pº de Las Doce Estrellas, 5-7

28042 Madrid

Spain

This medicinal product is authorised in the member states of the European Economic Area with the following names:

SpainVELETRI 0.5 mg powder and diluent for solution for infusion

VELETRI 1.5 mg powder and diluent for solution for infusion

NetherlandsVELETRI 0.5 mg, poeder in oplossingsmiddel voor oplossing voor infusie

VELETRI 1.5 mg, poeder in oplossingsmiddel voor oplossing voor infusie

FranceVELETRI 0.5 mg, poudre et solvant pour solution pour perfusion

VELETRI 1.5 mg, poudre et solvant pour solution pour perfusion

ItalyCARIPUL 0.5 mg, Polvere e Solvente per Soluzione per Infusione

CARIPUL 1.5 mg, Polvere e Solvente per Soluzione per Infusione

PolandVELETRI 0.5 mg proszek i rozpuszczalnik do sporzadzania roztworu do infuzji

VELETRI 1.5 mg proszek i rozpuszczalnik do sporzadzania roztworu do infuzji

PortugalVELETRI de 0.5 mg, Pó e Solvente para Solução para Perfusão

VELETRI de 1.5 mg, Pó eSolvente para Solução para Perfusão

Last update of this leaflet: October 2022.

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This information is intended solely for healthcare professionals:

1. INFORMATION FOR HEALTHCARE PROFESSIONALS

Dialysis

There are 2pack sizes available for use in the treatment of dialysis:

• 1 vial containing VELETRI sterile lyophilisate, equivalent to 0.5mg of VELETRI supplied with a bottle of 100ml of diluent.

• 1 vial containing VELETRI sterile lyophilisate, equivalent to 0.5mg of VELETRI supplied alone.

Reconstitution:

Draw 5ml of diluent into a sterile syringe, inject the contents of the syringe into the vial containing VELETRI and agitate gently until the powder has dissolved.The reconstituted solution should be examined before proceeding to its dilution. Its use is prohibited in case it presents particles or alteration of the colour.The elimination of the unused reconstituted solution will be carried out in accordance with local regulations.

Dilution:

The reconstituted solution should be diluted immediately to the final concentration. Any subsequent dilution should be carried out with the same diluent used for the reconstitution of the sterile lyophilisate powder.

Calculation of the infusion rate:

The infusion rate can be calculated from the following formula:

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

Pulmonary arterial hypertension

There are 4pack sizes available for use in the treatment of pulmonary arterial hypertension:

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

Initially, the pack containing the parenteral diluent should be used. During chronic treatment with VELETRI, the final concentration of the solution can be increased by adding another vial of 0.5mgor 1.5mgof VELETRI lyophilisate.

Reconstitution:

Draw 5ml of diluent into a sterile syringe, inject the contents of the syringe into the vial containing VELETRI and agitate gently until the powder has dissolved.The reconstituted solution should be examined before proceeding to its dilution. Its use is prohibited in case it presents particles or alteration of the colour.The elimination of the unused reconstituted solution will be carried out in accordance with local regulations.

Dilution:

The reconstituted solution should be diluted immediately to the final concentration. Any subsequent dilution should be carried out with the same diluent used for the reconstitution of the sterile lyophilisate powder.

When VELETRI is administered chronically, it should be prepared in a suitable drug administration device for the infusion pump.

Compatible infusion pumps for the administration of VELETRI include:

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

Manufactured by Smiths Medical.

Compatible accessories for the infusion pumps in the administration of VELETRI include:

• Disposable CADD medication cassette 50ml and 100ml of Smiths Medical.
• CADD infusion set with in-line filter 0.2micras (CADD extension set with male luer, 0.2micras air elimination filter, clamp and integral anti-reflux valve with male luer) of Smiths Medical.

Based on the available data from internal tests and the manufacturer's instructions for use of the accessories, the following materials are possibly compatible for the preparation and administration:

• Acrylics
• Acrylonitrile butadiene styrene (ABS)
• Poly carbonate
• Polyethersulfone
• Polpropylene
• Polytetrafluoroethylene (PTFE)
• Polyurethane
• Chlorinated polyvinyl chloride (PVC) (plasticised with DEHP)
• Silicone

The compatibility of terephthalate of polyethylene (PET) and terephthalate of polyethylene glycol (PETG) with VELETRI is unknown, as these materials have not been tested with VELETRI, so their use is not recommended.

Only infusion pumps with an in-line filter of 0.22micras located between the infusion pump and the catheter should be used. It is recommended to use filters with hydrophilic polyethersulfone membrane. The infusion pump and the in-line filter should be changed at least every 48hours.

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

Table1 provides examples for the preparation of frequently used concentrations of VELETRI solutions. Each vial is for single use.

VELETRI diluted to the final concentration in the drug administration device as indicated can be administered immediately at room temperature (25ºC) or, if stored, for a maximum of 8días at a temperature of 2ºC to 8ºC, according to the conditions of use indicated in Table2.

Do not expose the completely diluted solution to direct sunlight.

Special precautions for storage

This medicinal product does not require any special storage temperature. Do not freeze.

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

The reconstitution and dilution should be carried out immediately before administration.

Solutions of epoprostenol diluted for the treatment of pulmonary arterial hypertension, prepared immediately before use, can be administered immediately at 25ºC, or stored in the drug administration device to protect them from light for a maximum of 8días at a temperature of 2ºC to 8ºC, according to the conditions of use indicated in Table 2.

For detailed and updated information on this medicinal product, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/