Veletri

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

• 1. What VELETRI is and what it is used for
• 2. 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 widen 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 widens the blood vessels, which reduces the blood pressure in the lungs. VELETRI is also used to prevent blood clotting during haemodialysis when heparin cannot be used.

2. 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 oedema(fluid in the lungs) after starting treatment.

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

Warnings and precautions

Before starting VELETRI, you must discuss this with your doctor. Before starting VELETRI, your doctor must know:

• If you have any bleeding problems.

Skin damage at the injection site

VELETRI is given 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.

This can then lead to blistering and peeling of the skin. While using VELETRI, you must check the injection site carefully. You must contact the hospital immediatelyfor advice if the injection site becomes painful or swollen, or if blisters or peeling of the skin occur.

Effect of VELETRI on blood pressure and heart rate

VELETRI can cause your heart to beat faster or slower. It can also cause a severe drop 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 get these symptoms. This may require a reduction in dose or stopping the infusion.

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 the medicines you are taking, or have recently taken, and any you plan to take, including those obtained without a prescription. Some medicines can affect the way VELETRI works, or increase the risk of side effects. VELETRI can also affect the way other medicines work. 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 called NSAIDs);
• digoxin (a medicine used to treat heart conditions). Tell your doctor or pharmacistif you are taking any of these medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, 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 get worse during pregnancy. It is not knownwhether the ingredients of VELETRI pass into breast milk. Do not breast-feedwhile 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, and is therefore considered to be essentially 'sodium-free'.

3. How to use VELETRI

This medicine must always be used exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. VELETRI is provided as a powder in a small glass vial. Before use, the powder must be mixed with a liquid. VELETRI must not be given as a rapid injection into a vein. It must always be given as a slow infusion into a vein (drip). Your doctor will decide what dose of VELETRI you should have. The amount of medicine you are given will depend on your body weight and the type of condition you are being treated for. Depending on how you respond to the treatment, the dose may be increased or decreased. VELETRI is given as a slow infusion into a vein.

Pulmonary arterial hypertension

The first time you are given VELETRI, it will be in a hospital. This is because your doctor needs to monitor your condition and find the best dose for you. Treatment starts with an infusion (drip) of VELETRI. The dose of VELETRI is increased until your symptoms are relieved or disappear, and any side effects are manageable. Once the correct dose has been found, you will have a permanent catheter inserted into a vein. Treatment can then be continued using an infusion pump.

Haemodialysis

You will be given VELETRI during haemodialysis.

Using VELETRI at home (for pulmonary arterial hypertension only)

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 be given information on how to stop the treatment if necessary. Stopping VELETRI must be done gradually. It is very important to follow allof the instructions carefully. VELETRI is provided as a powder in a glass vial. Before use, the powder must be mixed with a suitable liquid. This liquid does not contain preservatives. If any liquid is left over, it must be thrown away.

Caring for the catheter

If you have a permanent catheter inserted into a vein, it is very importantto keep the area clean to avoid infection. Your doctor or nurse will instruct you on how to clean the catheter and the area around it. It is very important to follow allof these instructions carefully. It is also very importantto follow any instructions about changing the infusion bag (cassette) and to always use an infusion set with a filter, as instructed by your doctor, to reduce the risk of infection. When reconnecting the extension set, always make sure that any air bubbles have been removed to avoid fluid accumulating in the space between the extension set and the connectors of the injection tubes, as this can damage the materials.

Overdose

Seek medical help immediatelyif you think you have used 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

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

Stopping VELETRI

Stopping VELETRI must be done gradually. If the treatment is stopped too quickly, you may get severe side effects, including dizziness, weakness, and difficulty breathing. If you have any problems with the infusion pump or catheter that cause the treatment to be stopped, you must 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, VELETRI 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,
• diarrhoea,
• flushing.

Common side effects

May affect up to 1 in 10 people:

• blood infection (septicaemia),
• rapid heart rate,
• slow heart rate,
• low blood pressure,
• easy bruising or bleeding from different sites (e.g. nosebleeds, bleeding gums) and purple spots,
• abdominal discomfort or stomach 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

• low platelet count (reduced number of 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 catheter.

Other side effects

Frequency not known:

• enlarged or overactive spleen,
• fluid in the lungs (pulmonary oedema),
• high 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 Yellow Card Scheme. 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 must be diluted to the final concentration (see section 7). The storage conditions for the reconstituted solution and the diluted solution 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 epoprostenol sodium, equivalent to 0.5 mg epoprostenol. One ml of the reconstituted solution contains 0.1 mg 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 epoprostenol sodium, equivalent to 1.5 mg epoprostenol. One ml of the reconstituted solution contains 0.3 mg 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 colourless glass (Type I) closed with a rubber stopper and an aluminium 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

Haemodialysis

One presentation is available for use in haemodialysis, containing:

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

Reconstitution:

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

Dilution:

After reconstitution, the solution must be diluted to the final concentration. The same diluent used for reconstitution of the lyophilised powder should be used for further dilution. The reconstituted solution of VELETRI should be prepared immediately before use.

Calculation of infusion rate:

The infusion rate can be calculated using the following formula: Infusion rate (ml/min) = Dose (ng/kg/min) x body weight (kg) / Concentration of solution (ng/ml) Infusion rate (ml/hour) = infusion rate (ml/min) x 60

Pulmonary arterial hypertension

Two presentations are available for use in the treatment of pulmonary arterial hypertension, containing:

• one vial containing sterile, lyophilised VELETRI equivalent to 0.5 mg VELETRI.
• one vial containing sterile, lyophilised VELETRI equivalent to 1.5 mg VELETRI.

Reconstitution:

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

Dilution:

After reconstitution, the solution must be diluted to the final concentration. The same diluent used for reconstitution of the lyophilised powder should be used for further dilution. The solution of VELETRI for long-term infusion should be prepared in a reservoir for administration with an infusion pump. Suitable ambulatory infusion pumps for administration of VELETRI include: CADD-Legacy 1, CADD-Legacy PLUS, CADD-Solis VIP (variable infusion profile), manufactured by Smiths Medical. The following infusion sets have been found to be compatible with VELETRI: Single-use reservoir cassette for CADD, 50 ml or 100 ml, manufactured by Smiths Medical. CADD infusion set with 0.2 micron in-line filter (CADD infusion set with male luer connector, air-in-line filter, 0.2 micron filter, clamp, and built-in anti-siphon valve with male luer connector), manufactured by 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 (ABS) terpolymer, Polycarbonate, Polyethersulfone, Polypropylene, Polytetrafluoroethylene (PTFE), Polyurethane, Polyvinyl chloride (PVC) (plasticised with DEHP), Silicon. 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. It is recommended to use filters with a hydrophilic membrane made of polyethersulfone. The infusion set and in-line filter must be changed every 48 hours or more frequently. The vial containing 0.5 mg epoprostenol must be used to prepare solutions with a final concentration below 15,000 ng/ml. In Table 1, examples are given of how to prepare commonly used concentrations of VELETRI solutions. Each vial is for single use only.

Table 1: Commonly used concentrations – examples of reconstitution and dilution

VELETRI solution with a final concentration, once diluted, may 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 must be diluted to the final concentration. Reconstitution and dilution should be carried out immediately before use. The freshly prepared diluted solution of epoprostenol for the treatment of pulmonary arterial hypertension may 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.