VELETRI 0.5 mg Powder

Contents of the leaflet

1. Package Leaflet: Information for the User
2. VELETRI, 0.5 mg, powder for solution for infusion
3. VELETRI, 1.5 mg, powder for solution for infusion
   1. Read all of this leaflet carefully before using this medicine because it contains important information for you.
   2. Contents of the pack and other information
4. What VELETRI is and what it is used for
5. What you need to know before you use VELETRI
   1. When not to use VELETRI
   2. Warnings and precautions
   3. Skin damage at the injection site
   4. Effect of VELETRI on blood pressure and heart rate
   5. Children and adolescents
   6. Other medicines and VELETRI
   7. Pregnancy and breastfeeding
   8. Driving and using machines
   9. VELETRI contains sodium
6. How to use VELETRI
   1. Pulmonary arterial hypertension
   2. Hemodialysis
   3. Using VELETRI at home (only for pulmonary arterial hypertension)
   4. Care of the infusion catheter
   5. Overdose of VELETRI
   6. Missing a dose of VELETRI
   7. Stopping VELETRI
7. Possible side effects
   1. Very common side effects
   2. Common side effects
   3. Common side effects that may be detected in blood tests
   4. Uncommon side effects
   5. Rare side effects
   6. Very rare side effects
   7. Other side effects
   8. Reporting of side effects
8. How to store VELETRI
9. Contents of the pack and other information
   1. What VELETRI contains
   2. What VELETRI looks like and contents of the pack
   3. Marketing Authorisation Holder
   4. Manufacturer
   5. This medicinal product is authorised in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the leaflet: 10/2022
10. INFORMATION FOR HEALTHCARE PROFESSIONALS
    1. Hemodialysis
    2. Reconstitution:
    3. Dilution:
    4. Table 1: Common concentrations – examples of reconstitution and dilution
    5. Table 2: Maximum infusion time (in hours) at room temperature (25°C) for fully diluted solutions stored in the infusion reservoir.
    6. Special precautions for storage

Package Leaflet: Information for the User

VELETRI, 0.5 mg, powder for solution for infusion

VELETRI, 1.5 mg, powder for solution for infusion

Epoprostenol

Read all of this leaflet carefully before 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 and other information

• 1. What VELETRI is and what it is used for
• 2. What you need to know before you use VELETRI
• 3. How to use VELETRI
• 4. Possible side effects
• 5. How to store VELETRI
• 6. 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. These medicines prevent blood clotting and dilate blood vessels. VELETRI is used to treat a condition called pulmonary arterial hypertension. This is a condition where the blood pressure in the blood vessels of the lungs is too high. VELETRI dilates the blood vessels, which reduces the blood pressure in the lungs. VELETRI is also used to prevent blood clotting during hemodialysis when heparin cannot be used.

2. What you need to know before you use VELETRI

When not to use VELETRI

• If you are allergic toepoprostenol or any of the other ingredients of this medicine (listed in section 6);
• if you have heart failure;
• if you have pulmonary edema(fluid accumulation in the lungs) after starting treatment.

If you think any of these conditions apply to you, do not use VELETRIbefore consulting your doctor.

Warnings and precautions

Before starting treatment with VELETRI, discuss it with your doctor. Before starting treatment with VELETRI, your doctor must know:

• if you have any bleeding problems.

Skin damage at the injection site

VELETRI is administered into a vein. It is very important that the medicine does not leak out of the vein into the surrounding tissues. If this happens, it can cause skin damage. The symptoms of such damage are:

• tenderness (pain when pressed);
• burning;
• stinging;
• swelling;
• redness.

Then, blisters and skin peeling may occur. While using VELETRI, it is essential to monitor the injection site. You should contact the hospital immediatelyfor advice if the injection site becomes painful or swollen, or if blisters or skin peeling occur.

Effect of VELETRI on blood pressure and heart rate

VELETRI may cause an increase or decrease in heart rate. It may also cause a significant decrease in blood pressure. While using VELETRI, your heart rate and blood pressure will be monitored. Symptoms of low blood pressure include dizzinessand fainting. Tell your doctorif you experience these symptoms. This may require a decrease in the dose of VELETRI or discontinuation of treatment.

Children and adolescents

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

Other medicines and VELETRI

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription. Some medicines may affect the action of VELETRI or increase the risk of side effects. VELETRI may also affect the action of other medicines 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;
• anti-inflammatory and pain-relieving medicines(also known as NSAIDs);
• digoxin(a medicine used to treat heart conditions). Tell your doctor or pharmacistif 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 have a baby, ask your doctor or pharmacist for advice before using this medicine. The symptoms of your condition may worsen during pregnancy. It is not knownwhether the ingredients of VELETRI pass into breast milk. Do not breastfeedwhile using VELETRI.

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.

VELETRI contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, which is essentially sodium-free.

3. How to use VELETRI

Always use this medicine exactly as your doctor or pharmacist has told you. If you are unsure, ask your doctor or pharmacist. VELETRI is supplied as a powder in a small glass vial. Before use, the powder must be dissolved. VELETRI should not be administered as a rapid injection into a vein. It should always be administered as an intravenous infusion. Your doctor will decide what dose of VELETRI is suitable for you. The amount of medicine given depends on your body weight and the type of condition you have. Depending on your response to treatment, the dose may be increased or decreased. VELETRI is administered as a slow infusion into a vein.

Pulmonary arterial hypertension

The medicine will be given to you for the first time in a hospital. This is because your doctor needs to monitor your condition and determine the best dose for you. Treatment starts with an infusion of VELETRI. The dose is increased until your symptoms are relieved or disappear, and side effects are manageable. After the right dose has been determined, you will have a permanent catheter inserted into a vein. Treatment can be continued using an infusion pump.

Hemodialysis

You will receive VELETRI during the dialysis procedure.

Using VELETRI at home (only for pulmonary arterial hypertension)

If you are using VELETRI at home, you will be instructed by your doctor or nurse on how to prepare and use VELETRI. You will also receive information on how to stop treatment if necessary. Stopping VELETRI must be done gradually. It is crucial to follow allinstructions carefully. VELETRI is supplied as a powder in a glass vial. Before use, the powder must be dissolved in the appropriate liquid. This liquid does not contain preservatives. If any unused liquid remains, it should be discarded.

Care of the infusion catheter

If you have a permanent catheter inserted into a vein, it is very importantto keep the site clean to avoid infection. Your doctor or nurse will instruct you on how to clean the catheter and the area around it. It is crucial to follow allthese instructions carefully. It is also very importantto follow the instructions for changing the drug reservoir in the pump (cassette) and to always use an infusion set with a filter, as advised by your doctor, to reduce the risk of infection. When reconnecting the extension set, always make sure that any potential drops have been wiped away to prevent fluid from accumulating in the external space between the extension set and the injection ports, as this can damage the materials.

Overdose of VELETRI

Seek medical help immediatelyif you think you have taken or received too much VELETRI. Symptoms of overdose may include headache, nausea, vomiting, rapid heart rate, feeling hot or tingling, or feeling faint (weakness, dizziness).

Missing a dose of VELETRI

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

Stopping VELETRI

Stopping VELETRI must be done gradually. If treatment is stopped too quickly, you may experience severe side effects, including dizziness, weakness, and difficulty breathing. If you have problems with the infusion pump or catheter that lead to stopping VELETRI, contact your doctor, nurse, or hospital staff immediately. If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common side effects

May affect more than 1 in 10 people:

• headache,
• jaw pain,
• pain,
• vomiting,
• nausea,
• diarrhea,
• flushing (redness of the face).

Common side effects

May affect up to 1 in 10 people:

• blood infection (sepsis),
• rapid heart rate,
• slow heart rate,
• low blood pressure,
• easy bruising or bleeding from different sites (e.g., nose, gums) and petechiae (small red or purple spots on the skin),
• abdominal discomfort or abdominal pain,
• chest pain,
• joint pain,
• feeling anxious or nervous,
• rash,
• pain at the injection site.

Common side effects that may be detected in blood tests

• decrease in platelet count (cells involved in blood clotting).

Uncommon side effects

May affect up to 1 in 100 people:

• sweating,
• dry mouth.

Rare side effects

May affect up to 1 in 1,000 people:

• infection at the injection site.

Very rare side effects

May affect up to 1 in 10,000 people:

• feeling of tightness in the chest,
• feeling tired or weak,
• feeling agitated,
• pale skin,
• redness at the injection site,
• overactive thyroid gland,
• blockage of the infusion catheter.

Other side effects

Frequency not known:

• enlarged or overactive spleen,
• fluid accumulation in the lungs (pulmonary edema),
• increased blood sugar levels,
• fluid accumulation in the abdomen (ascites),
• the heart pumping too much blood, leading to shortness of breath, feeling tired, swelling of the legs and abdomen due to fluid accumulation, and 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 national reporting system listed in the website. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store VELETRI

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month. There are no special storage instructions for this medicine (before reconstitution). Do not freeze. After reconstitution, the solution should be diluted immediately to the final concentration (see section 7). The storage conditions for the reconstituted solution and after dilution are stated in section 7. Do not use this medicine if you notice any particles in the solution after reconstitution. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What VELETRI contains

VELETRI 0.5 mg, powder for solution for infusion.

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

VELETRI 1.5 mg, powder for solution for infusion.

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

The other ingredients are sucrose, arginine, and sodium hydroxide (for pH adjustment).

What VELETRI looks like and contents of the pack

White or off-white powder in a vial made of colorless glass (type I) closed with a rubber stopper and an aluminum flip-off cap. Each pack contains one vial containing 0.5 mg of powder. Each pack contains one vial containing 1.5 mg of powder.

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 medicine, contact the local representative of the Marketing Authorisation Holder: Janssen-Cilag Polska Sp. z o.o., tel. +48 22 237 60 00

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Belgium: VELETRI, Czech Republic: VELETRI, France: VELETRI, Spain: VELETRI, Netherlands: VELETRI, Poland: VELETRI, Portugal: VELETRI, United Kingdom: VELETRI, Italy: CARIPUL

Date of last revision of the leaflet: 10/2022

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Information intended for healthcare professionals only:

7. INFORMATION FOR HEALTHCARE PROFESSIONALS

Hemodialysis

One type of packaging is available for use in hemodialysis, containing:

• one vial containing sterile, lyophilized VELETRI equivalent to 0.5 mg of VELETRI.

Reconstitution:

Using a sterile syringe, draw 5 ml of sterile water for injection or 0.9% sodium chloride injection, inject the contents of the syringe into the vial containing VELETRI, and gently swirl until the powder is completely dissolved. The reconstituted solution should be inspected before further dilution. Do not administer if a change in color or presence of particles is observed. Any unused prepared solution should be disposed of in accordance with local regulations.

Dilution:

After reconstitution, the solution should be diluted immediately to the final concentration. The same diluent used for reconstitution of the lyophilized powder should be used for further dilution. The VELETRI solution intended for prolonged administration should be prepared in an infusion reservoir compatible with the infusion pump being used. Suitable ambulatory infusion pumps for administering VELETRI include:

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

Manufactured by Smiths Medical. The following infusion set components have been found to be compatible with VELETRI:

• Single-use cassette-style reservoir for CADD, 50 ml or 100 ml, from Smiths Medical.
• CADD infusion set with 0.2-micron in-line filter (CADD infusion set with male luer connector, air-eliminating filter, 0.2 micron, with clamp and built-in anti-siphon valve with male luer connector) from Smiths Medical.

Based on available data from internal studies and manufacturer's instructions for accessories, materials for preparation and administration that may be compatible include:

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

It is not known whether polyethylene terephthalate (PET) and polyethylene terephthalate glycol (PETG) are compatible with VELETRI, as these materials have not been tested with VELETRI, and therefore, their use is not recommended. Only infusion sets with a 0.22-micron in-line filter should be used, positioned between the infusion pump and the catheter. It is recommended to use filters with a hydrophilic membrane made of polyethersulfone. The infusion set and in-line filter must be replaced every 48 hours or more frequently. The vial containing 0.5 mg of epoprostenol must be used to prepare solutions with a final concentration below 15,000 ng/ml. The following table provides examples of preparing commonly used concentrations of VELETRI solutions. Each vial is for single use only.

Table 1: Common concentrations – examples of reconstitution and dilution

VELETRI solution diluted to the final concentration in the infusion reservoir can be administered immediately at room temperature (25°C) or stored in the infusion reservoir for up to 8 days at 2°C to 8°C, in accordance with the conditions specified in Table 2.

Table 2: Maximum infusion time (in hours) at room temperature (25°C) for fully diluted solutions stored in the infusion reservoir.

Do not expose the fully diluted solution to direct sunlight.

Special precautions for storage

There are no special storage instructions for the medicinal product. Do not freeze. After reconstitution, the solution should be diluted immediately to the final concentration. Reconstitution and dilution should be performed immediately before use. The freshly prepared diluted solution of epoprostenol intended for the treatment of pulmonary arterial hypertension can be administered immediately at 25°C or stored in the infusion reservoir for up to 8 days at 2°C to 8°C, in accordance with the conditions specified in Table 2.