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How to use PEPAXTI 20 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Pepaxti 20 mg powder for concentrate for solution for infusion

Melfalán flufenamida

Read all of this leaflet carefully before you are given 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 or nurse.
If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

What is Pepaxti and what is it used for
What you need to know before you start using Pepaxti
How to use Pepaxti
Possible side effects
Storage of Pepaxti
Contents of the pack and further information

1. What is Pepaxti and what is it used for

Pepaxti belongs to a group of cancer medicines called alkylating agents. It works by attaching to the DNA (the genetic instructions necessary for cells to survive and multiply) and damaging it, thus helping to stop the growth of cancer cells.

Pepaxti is given with the steroid dexamethasone to treat adults with multiple myeloma, a blood cancer. It is used when the disease does not respond to at least three types of cancer medicines. If you have been treated with a stem cell transplant (a procedure in which the cells that produce blood are removed and replaced), the time until the multiple myeloma comes back after the transplant must be at least 3 years.

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

Do not use Pepaxti

if you are allergic to melfalán flufenamida or to any of the other ingredients of this medicine (listed in section 6);
if you are breast-feeding.

Warnings and precautions

Talk to your doctor or nurse before you are given Pepaxti.

Bleeding and unusual bruising and low platelet count (blood cells)

Pepaxti may reduce the number of blood cells called platelets, which help the blood to clot. Tell your doctor or nurse immediately if you start bleeding, for example, if you have a nosebleed or notice bruising on your skin.

Fever and low white blood cell count

Pepaxti may reduce the number of white blood cells, which are important for fighting infections. Tell your doctor or nurse immediately if you have symptoms of infection, such as fever, chills or cough.

Low red blood cell count

Pepaxti may reduce the number of red blood cells, which carry oxygen to the cells in your body. Your doctor will take blood samples from you regularly to check your blood cells. Tell your doctor or nurse immediately if you feel weak or tired, if you look pale or if you feel short of breath.

Infections

Infections such as pneumonia (lung infection) and upper respiratory tract infection (which causes symptoms similar to a cold) are very common with Pepaxti. Tell your doctor or nurse immediately if you have a fever or other signs of infection. Your doctor may recommend preventive antibiotics to reduce the risk of developing infections.

Risk of diarrhea, nausea or vomiting

Tell your doctor if you have diarrhea, nausea or vomiting.

Risk of blood clots

The use of Pepaxti in combination with dexamethasone may increase the risk of blood clots. Tell your doctor or nurse if you have ever had a blood clot in a vein (thrombosis). Tell your doctor or nurse immediately if you have swelling of a leg or arm, if you have difficulty breathing or if you have chest pain.

Risk of additional cancer

It is important to note that patients with multiple myeloma treated with Pepaxti may develop other types of cancer, so your doctor must carefully evaluate the benefits and risks for you when prescribing this medicine.

Kidney disease

If you have reduced kidney function, the adverse effects of Pepaxti on your blood cells may be worse. There is very little information available on the use of the medicine in patients with severe kidney failure to recommend a safe and effective dose.

Vaccines

Vaccines that contain live but weakened organisms, known as live attenuated vaccines (such as measles, mumps and rubella vaccines), must not be used during treatment with Pepaxti, as they may cause infection. However, other types of vaccines known as inactivated vaccines or mRNA-based vaccines may be used. Tell your healthcare professional that you are being treated with Pepaxti before you are vaccinated.

Children and adolescents

Pepaxti is not indicated in children or adolescents under 18 years of age.

Other medicines and Pepaxti

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

This medicine is not recommended during pregnancy unless clearly necessary. Avoid becoming pregnant while being treated with this medicine, as it may harm the fetus. Your doctor will explain the possible risks of using Pepaxti during pregnancy.

If you are a woman who can become pregnant:

Your doctor will ask you to have a pregnancy test before starting treatment with Pepaxti.
You must use an effective method of contraception during treatment and for 6 months after the last dose of Pepaxti. Ask your doctor about effective contraceptive methods that may be suitable for you.

If you are a man who can father a child:

You must use an effective method of contraception during treatment and for 6 months after the last dose of Pepaxti.

Breast-feeding

Do not breast-feed during treatment with Pepaxti, as it may be harmful to your baby.

Fertility

Pepaxti may affect the ovaries or sperm, causing infertility (inability to have children). Women may experience interruption of their periods. In men, the inability to father a child (sterility) due to a lack of sperm may be permanent. Ask your doctor about sperm preservation before treatment.

Driving and using machines

Pepaxti may cause nausea and dizziness, which may reduce your ability to drive or use machines.

3. How to use Pepaxti

Pepaxti is prepared as a solution and will be given to you by your doctor or nurse through a drip in a vein (intravenous infusion) over 30 minutes. Your doctor will decide the correct dose of Pepaxti. The recommended initial dose is 40 mg once every 4 weeks. If you weigh 60 kg or less, the recommended initial dose is 30 mg once every 4 weeks. Treatment will continue as long as it is beneficial to you and you do not have unacceptable side effects. As part of your treatment, you will also take another medicine, dexamethasone, by mouth.

If you are given too much Pepaxti

This medicine will be given to you by your doctor or nurse. In the unlikely event that you are given too much (an overdose), your doctor will examine you, including taking blood samples to check your blood cells.

If you miss a dose of Pepaxti

It is very important that you attend all your appointments to ensure your treatment works. If you miss an appointment, contact your doctor or hospital as soon as possible.

4. Possible side effects

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

Tell a doctor immediately if you notice any of the following serious side effects: you may need urgent medical treatment:

Fever, chills, sore throat, cough or any other sign of infection (due to a lack of white blood cells called neutrophils, which fight infections).
Rapid breathing, rapid heartbeat, fever and chills, passing little or no urine, nausea and vomiting, confusion, loss of consciousness (due to a severe bacterial infection of the blood called sepsis or septic shock).
Bleeding or bruising without cause, such as nosebleeds (due to a low platelet count [thrombocytopenia]).
Difficulty breathing (due to a severe chest infection, inflammation of the lungs or blood clots in the lungs).
Pain and swelling of the legs or arms, especially in the lower leg or calf (caused by blood clots).

Other side effects that may occur

Very common (may affect more than 1 in 10 people):

Reduced number of platelets in the blood (thrombocytopenia)
Lower number of a type of white blood cell called neutrophils (neutropenia)
Reduced number of red blood cells that carry oxygen in the blood (anemia), which causes weakness and tiredness.
Lung infection (pneumonia)
Upper respiratory tract infection with, for example, fever, cough and cold-like symptoms
Diarrhea
Nausea
Fever
Cough
Shortness of breath
Extreme tiredness (fatigue)
Weakness

Common (may affect up to 1 in 10 people):

Severe bacterial infection of the blood (sepsis)
Fever together with a reduced number of some white blood cells (neutropenia)
Lower number of a type of white blood cell called lymphocytes (lymphopenia), which also help fight infections
General reduction in the number of white blood cells
Loss of appetite
Low potassium levels (may cause muscle weakness and irregular heartbeats)
High levels of uric acid in the blood (may cause gout and kidney problems)
Headache
Dizziness
Difficulty breathing when exercising
Nosebleeds
Vomiting
Deep vein thrombosis (blood clot in a vein)
Bruising

Uncommon (may affect up to 1 in 100 people):

Severe bacterial infection of the blood with dangerously low blood pressure (septic shock) that can be life-threatening or even fatal
Blood clots in the lungs
A type of blood cancer called myelodysplastic syndrome (MDS)
A type of blood cancer called acute myeloid leukemia (AML)

Your doctor or nurse may give you additional medicines to treat your symptoms and/or prevent side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pepaxti

Pepaxti will be stored in the hospital or clinic, so these instructions are intended for healthcare professionals.

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 vial label and carton after EXP. The expiry date refers to the last day of the month stated.

Store in a refrigerator (2°C - 8°C). Do not freeze.

Store in the original package to protect from light.

Medicines should not be disposed of via wastewater or household waste. This will help protect the environment.

6. Container Content and Additional Information

Pepaxti Composition

The active ingredient is melfalán flufenamida. One vial contains 20 mg of melfalán flufenamida (in the form of hydrochloride).
The other component is sucrose (sugar).

Product Appearance and Container Content

Pepaxti is a white to off-white powder contained in a glass vial.

Each box contains one vial.

Marketing Authorization Holder

Oncopeptides AB (publ)

Luntmakargatan 46

111 37 Stockholm

Sweden

Manufacturer

Eumedica NV

Chemin de Nauwelette 1

7170 Manage

Belgium

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Oncopeptides AB (publ)

Email: medinfo@oncopeptides.com

Date of the last revision of this prospectus: 01/2025.

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu

On the European Medicines Agency website, you can find this prospectus in all the languages of the European Union/European Economic Area.

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This information is intended only for healthcare professionals:

Step-by-step instructions for use and handling, reconstitution, and administration

Pepaxti must be prepared by a healthcare professional using an aseptic technique to ensure the sterility of the prepared solution.

Additional solvents required for preparation:

5% glucose injectable/perfusion solution (room temperature).

250 ml bag of 9 mg/ml (0.9%) sodium chloride injectable solution, cold (between 2 °C and 8 °C) (refrigerate for at least 4 hours).

Table 1 Volumes of Dilution per Pepaxti Dose

Volume Description	Pepaxti Dose
40 mg (2 vials)	30 mg (1.5 vials)	20 mg (1 vial)	15 mg (0.75 vial)
Volume of reconstituted Pepaxti solution needed for the final product	80 ml	60 ml	40 ml	30 ml
Total final volume of the perfusion bag after dilution	250 ml	230 ml	210 ml	200 ml
Pepaxti concentration after dilution	0.16 mg/ml	0.13 mg/ml	0.10 mg/ml	0.08 mg/ml

Preparation Steps

Read the complete instructions before starting preparation.

Steps 3 to 5 must be completed within 30 minutes.

Reconstitution and Dilution Steps

Step 1

Determine the number of vials needed for the dose according to Table 1 "Volumes of Dilution per Pepaxti Dose". Place the vial(s) at room temperature for at least 30 minutes.

Step 2

Vigorously shake the vial or vortex to break up the lyophilized powder cake into a loose powder.

Steps 3 to 5 must be performed within 30 minutes

Third Stage

For a Pepaxti dose of 40 mg	For a Pepaxti dose of 30 mg	For a Pepaxti dose of 20 mg	For a Pepaxti dose of 15 mg
Reconstitute aseptically each of the 2 vials with 40 ml of 5% glucose perfusion solution to obtain a final concentration of 0.5 mg/ml.	Reconstitute aseptically each of the 2 vials with 40 ml of 5% glucose perfusion solution to obtain a final concentration of 0.5 mg/ml.	Reconstitute aseptically 1 vial with 40 ml of 5% glucose perfusion solution to obtain a final concentration of 0.5 mg/ml.	Reconstitute aseptically 1 vial with 40 ml of 5% glucose perfusion solution to obtain a final concentration of 0.5 mg/ml.

Ensure that the 5% glucose perfusion solution is at room temperature (between 20 °C and 25 °C). Vigorously shake the vial or vials until the solution is clear.

Allow the vial(s) to stand to permit air bubbles to dissipate and confirm that a clear solution has been obtained.

Step 4

Withdraw 80 ml from a refrigerated (between 2 °C and 8 °C) 250 ml bag of 9 mg/ml (0.9%) sodium chloride injectable solution. Discard the withdrawn 80 ml.

Step 5

For a Pepaxti dose of 40 mg	For a Pepaxti dose of 30 mg	For a Pepaxti dose of 20 mg	For a Pepaxti dose of 15 mg
Withdraw 80 ml of reconstituted solution from the Pepaxti vials and transfer it to an intravenous (IV) injectable solution containing 9 mg/ml (0.9%) sodium chloride to obtain a final concentration of 0.16 mg/ml.	Withdraw 60 ml of reconstituted solution from the Pepaxti vials and transfer it to an intravenous (IV) injectable solution containing 9 mg/ml (0.9%) sodium chloride to obtain a final concentration of 0.12 mg/ml.	Withdraw 40 ml of reconstituted solution from the Pepaxti vials and transfer it to an intravenous (IV) injectable solution containing 9 mg/ml (0.9%) sodium chloride to obtain a final concentration of 0.10 mg/ml.	Withdraw 30 ml of reconstituted solution from the Pepaxti vials and transfer it to an intravenous (IV) injectable solution containing 9 mg/ml (0.9%) sodium chloride to obtain a final concentration of 0.08 mg/ml.

Discard any unused portion remaining in the vial or vials.

Gently invert the bag to mix the solution. Do not shake. Check that the solution is clear and colorless or pale yellow. Do not use if solution discoloration or particles are observed.

Storage Periods

Pepaxti degrades in solution, especially at room temperature, and the storage periods of the diluted solution must not be exceeded.

For Immediate Administration

The perfusion of the diluted solution must start within 60 minutesof the start of reconstitution (step 3).

For Deferred Administration

If not used for immediate administration, the diluted solution must be stored in a refrigerator (between 2 °C and 8 °C) within 30 minutes of the initial reconstitution (step 3) and kept for a maximum of 6 hours.

Administration

Prior to administration, parenteral medications must be visually inspected for the presence of particles and color changes. Do not use if visibly opaque particles, discoloration, or foreign particles are observed.

Administration Steps

Step 6

Administer Pepaxti as a 30-minute intravenous perfusion through a peripheral venous line or a central venous access device, such as a PICC or a tunneled central venous catheter. If the perfusion bag has been refrigerated, allow it to reach room temperature (between 20 °C and 25 °C). Start the perfusion within 30 minutes of removing the diluted solution from the refrigerator.

Step 7

Once the Pepaxti perfusion is complete, flush the central catheter with a 9 mg/ml (0.9%) sodium chloride injectable solution.

Disposal

Pepaxti is a cytotoxic medication for single use. The procedure for the safe handling and disposal of nitrogen mustard analogs by healthcare professionals or medical personnel must be followed, and current recommendations for cytotoxic medications must be complied with. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

PEPAXTI 20 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION