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
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any possible adverse effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What VELETRI is and what it is used for
2. Important information before using 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 that inhibit blood clotting and dilate blood vessels.
VELETRI is used in the treatment of a lung disease called pulmonary arterial hypertension. This is a condition in which the blood pressure in the blood vessels of the lungs is too high. VELETRI dilates the blood vessels, thereby reducing blood pressure in the lungs.
VELETRI is also used to prevent blood clotting during hemodialysis when heparin cannot be used.

2. Important information before using VELETRI

When not to use VELETRI

• if the patient is allergic to epoprostenol or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has heart failure;
• if, after starting treatment, the patient develops fluid accumulation in the lungs causing shortness of breath.

If the patient believes any of the above situations apply, do not use
VELETRI before consulting a doctor.

Warnings and precautions

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

• whether the patient has any problems with bleeding.

Skin damage at the injection site
VELETRI is administered intravenously. It is very important that the medicine does not leak outside the vein into the surrounding tissues. If this occurs, skin damage may result. Signs of such damage include:

• tenderness (pain upon pressure);
• burning;
• stinging;
• swelling;
• redness.

This may progress to blister formation and skin peeling. The infusion site must be monitored carefully during VELETRI administration.
Contact the hospital immediately for advice if the infusion 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 increased or decreased heart rate. It may also cause excessive lowering of blood pressure. Heart rate and blood pressure will be monitored during VELETRI treatment. Symptoms of low blood pressure include dizziness and fainting.
Inform your doctor if such symptoms occur. This may require dose reduction or discontinuation of the medicine.

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 currently taking, have recently taken, or plan to take, including over-the-counter medicines.
Some medicines may affect the action of VELETRI or increase the likelihood of adverse effects. VELETRI may also affect the action of other medicines taken concurrently. These include:

• medicines used to treat high blood pressure;
• medicines used to prevent clot formation;
• medicines used to dissolve clots;
• anti-inflammatory and pain-relieving medicines (also known as NSAIDs);
• digoxin (a medicine used in the treatment of heart disease). Inform your doctor or pharmacist if you are taking any of these medicines.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine, as symptoms of the disease may worsen during pregnancy.
It is not known whether the components of VELETRI pass into human milk. Breastfeeding must be discontinued during treatment with VELETRI.

Driving and operating machinery
Treatment may affect the ability to drive or operate machinery.
Do not drive or operate machinery if the patient does not feel well.

VELETRI contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial and is therefore considered "sodium-free".

3. How to use VELETRI

This medicine should always be used as directed by your doctor or pharmacist. If you have any
doubts, consult your doctor or pharmacist.
VELETRI is supplied as a powder in a small glass vial. Before use, the powder must be dissolved.
VELETRI must not be administered as a rapid intravenous injection. It should always be given as an intravenous infusion (intravenous drip).
Your doctor will determine the appropriate dose of VELETRI for you. The dose administered depends on the patient's body weight and the type of disease. Depending on the patient's response to treatment, the dose may be increased or decreased.
VELETRI is administered by slow intravenous infusion.

Pulmonary arterial hypertension
VELETRI will initially be administered in a hospital setting. This is because your doctor needs to monitor your condition and determine the optimal dose.
Treatment is initiated with an infusion (intravenous drip) of VELETRI. The dose is gradually increased until symptoms are alleviated or resolve and side effects are manageable. Once the appropriate dose is established, a permanent intravenous catheter will be inserted.
Treatment may then continue using an infusion pump.

Hemodialysis
You will receive VELETRI during dialysis sessions.

Using VELETRI at home (only for the treatment of pulmonary arterial hypertension)
If you are self-administering VELETRI at home, you will be instructed by your doctor or nurse on how to prepare and administer the medicine. You will also receive information on how to discontinue treatment if necessary. Discontinuation of VELETRI must be done gradually. It is very important to strictly follow all instructions.
VELETRI is supplied as a powder in a glass vial. Before use, the powder must be dissolved in an appropriate solution. This solution does not contain preservatives. Any unused solution should be discarded.

Care of the drug administration catheter
If you have a permanent intravenous catheter, it is very important to keep the site clean to prevent infection. Your doctor or nurse will instruct you on how to clean the catheter and the surrounding area. It is essential to strictly follow all such instructions. It is also very important to strictly follow all instructions regarding changing the medication reservoir (cassette) in the pump and always use an infusion set with a filter, as directed by your doctor, to reduce the risk of infection. When reconnecting the extension set, always ensure that any droplets are removed so that no fluid remains in the external space between the extension set and the injection line connectors, as this could damage materials.

If you use more VELETRI than you should
Seek immediate medical help if you think you have used or been given too much VELETRI. Symptoms of overdose may include headache, nausea, vomiting, rapid heartbeat, feeling of warmth or tingling, and feeling faint (weakness, dizziness).

If you forget to use VELETRI
Do not use a double dose to make up for a missed dose.

Stopping VELETRI
Discontinuation of VELETRI must be done gradually. If treatment is stopped too quickly, serious side effects may occur, including dizziness, weakness, and difficulty breathing. If there are problems with the infusion pump or the catheter leading to interruption of VELETRI treatment, you must immediately contact your doctor, nurse, or hospital staff.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.

Very common adverse reactions
May occur in more than 1 in 10 patients:

• headache,
• jaw pain,
• pain,
• vomiting,
• nausea,
• diarrhoea,
• facial flushing (hot flushes).

Common adverse reactions
May occur in up to 1 in 10 patients:

• blood infection (sepsis),
• rapid heartbeat,
• slow heartbeat,
• low blood pressure,
• easier than usual bleeding from various sites (e.g. nose, gums) and bruising,
• abdominal discomfort or abdominal pain,
• chest pain,
• joint pain,
• feeling of anxiety, nervousness,
• rash,
• pain at injection site.

Common adverse reactions that may be detected in blood tests

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

Uncommon adverse reactions
May occur in up to 1 in 100 patients:

• sweating,
• dry mouth.

Rare adverse reactions
May occur in up to 1 in 1,000 patients:

• infection at the infusion site.

Very rare adverse reactions
May occur in up to 1 in 10,000 patients:

• feeling of chest tightness,
• feeling of fatigue, weakness,
• feeling of restlessness,
• skin pallor,
• redness at injection site,
• hyperthyroidism,
• blockage of the catheter used for administering the medicine.

Other adverse reactions
Frequency unknown:

• enlarged or overactive spleen,
• fluid accumulation in the lungs (pulmonary oedema),
• increased blood sugar (glucose) levels,
• ascites (accumulation of fluid in the abdominal cavity),
• excessive pumping of blood from the heart, causing shortness of breath, feeling of fatigue, swelling of legs and abdomen due to fluid accumulation, persistent cough,
• urticaria.

Reporting of adverse reactions

Immediately inform your doctor or nurse if any of the following symptoms occur, as they may indicate blood infection (sepsis), low blood pressure, or severe bleeding:

• the patient experiences rapid heartbeat, chest pain, or shortness of breath;
• the patient experiences dizziness or feeling faint, especially when standing up;
• the patient has fever or chills;
• the patient experiences more frequent or prolonged bleeding episodes.

If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to:

Department of Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse reactions can also be reported to the marketing authorisation holder.

Reporting adverse reactions helps to provide more information on the safety of the 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 stated on the carton after "EXP". The expiry date refers to the last day of the specified month.
Do not freeze.
After reconstitution, the solution must be immediately diluted to the final concentration (see Information for healthcare professionals).
For storage conditions of the medicinal solution after reconstitution and after dilution, see Information for healthcare professionals.
Do not use this medicine if any particulate matter is observed in the solution after reconstitution.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures 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, equivalent to 0.5 mg of epoprostenol. One ml of reconstituted solution contains 0.1 milligram 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, equivalent to 1.5 mg of epoprostenol. One ml of reconstituted solution contains 0.3 milligrams of epoprostenol (as epoprostenol sodium).

The other components are: sucrose, arginine, and sodium hydroxide (to adjust pH).
What VELETRI looks like and contents of the pack
White or almost 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 with 0.5 mg of powder.
Each pack contains one vial with 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 about this medicinal product, please 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 for marketing 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

Information intended exclusively for medical professionals:

INFORMATION INTENDED FOR MEDICAL PERSONNEL

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

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

Reconstitution:
Using a sterile syringe, withdraw 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection, inject the syringe contents into the vial containing the VELETRI product, and gently shake until the powder is completely dissolved. The solution after reconstitution must be inspected before further dilution. The product must not be administered if any change in solution color or presence of particulate matter is observed. Any unused portion of the prepared solution must be discarded in accordance with local regulations.

Dilution:
After reconstitution, the solution must be immediately diluted to the final concentration. The same diluent used for reconstitution of the sterile lyophilized powder must be used for further dilution.

Infusion rate calculation:
The infusion rate can be calculated using the following formula:

Dosing (ng/kg/min) × body weight (kg)
Infusion rate (ml/min) =
Concentration of solution (ng/ml)

Infusion rate (ml/hour) = infusion rate (ml/min) × 60

Pulmonary arterial hypertension
The following two types of packaging for use in the treatment of pulmonary arterial hypertension are available, containing:

• one vial containing sterile, lyophilized VELETRI product equivalent to 0.5 mg of VELETRI.
• one vial containing sterile, lyophilized VELETRI product equivalent to 1.5 mg of VELETRI.

Reconstitution:
Using a sterile syringe, withdraw 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection, inject the syringe contents into the vial containing the VELETRI product, and gently shake until the powder is completely dissolved. The solution after reconstitution must be inspected before further dilution. The product must not be administered if any change in solution color or presence of particulate matter is observed. Any unused portion of the prepared solution must be discarded in accordance with local regulations.

Dilution:
After reconstitution, the solution must be immediately diluted to the final concentration. The same diluent used for reconstitution of the sterile lyophilized powder must be used for further dilution.

The VELETRI solution intended for long-term administration should be prepared in an administration container compatible with the infusion pump used.

The following ambulatory pumps have been found suitable for administration of VELETRI:

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

Manufactured by Smiths Medical.

The following pump components have been found suitable for administration of VELETRI:

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

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

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

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

Only infusion sets with a 0.22 micron in-line filter placed between the infusion pump and the catheter may be used. Use of filters with a hydrophilic polyethersulfone membrane is recommended. The infusion set and in-line filter must be replaced every 48 hours or more frequently.

A vial containing 0.5 mg of epoprostenol must be used for the preparation of solutions with a final concentration below 15,000 ng/ml.

Table 1 provides examples of commonly used concentrations of VELETRI solution and methods of reconstitution and dilution. Each vial is for single use only.

Table 1: Commonly used concentrations – examples of reconstitution and dilution methods
Final concentration (ng/ml) Instructions:
3,000 ng/ml Dissolve the contents of one 0.5 mg vial in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection.
Withdraw 3 ml of the vial contents and dilute with the same diluent to a final volume of 100 ml.
5,000 ng/ml Dissolve the contents of one 0.5 mg vial in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection.
Transfer the entire contents of the vial and dilute with the same diluent to a final volume of 100 ml.
10,000 ng/ml Dissolve the contents of two 0.5 mg vials in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection for each vial.
Transfer the entire contents of the vials and dilute with the same diluent to a final volume of 100 ml.
15,000 ng/ml* Dissolve the contents of one 1.5 mg vial in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection.
Transfer the entire contents of the vial and dilute with the same diluent to a final volume of 100 ml.
30,000 ng/ml* Dissolve the contents of two 1.5 mg vials in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection for each vial.
Transfer the entire contents of the vials and dilute with the same diluent to a final volume of 100 ml.
30,000 ng/ml* Dissolve the contents of one 1.5 mg vial in 5 ml of sterile water for injection or 0.9% sodium chloride solution for injection.
Transfer the entire contents of the vial and dilute with the same diluent to a final volume of 50 ml.

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

Table 2: Maximum duration of administration (in hours) at room temperature (25°C) of fully diluted solutions stored in an administration container.

Do not expose the fully diluted solution to direct sunlight.
Special precautions for storage
Do not freeze.
After reconstitution, the solution should be immediately diluted to the final concentration.
Reconstitution and dilution must be performed immediately before use.
The freshly prepared diluted solution of epoprostenol for the treatment of pulmonary arterial
hypertension may be administered immediately at 25°C or stored in a drug delivery system container, protected from light, for up to 8 days at 2°C to 8°C, according to the conditions specified in Table 2.