Pepaxti: detailed information

Patient Information Leaflet

Pepaxti 20 mg powder for concentrate for solution for infusion

melflufenamide
Please read 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 questions, ask your doctor or nurse.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

What Pepaxti is and what it is used for
What you need to know before you are given Pepaxti
How Pepaxti is administered
Possible side effects
How to store Pepaxti
Contents of the pack and other information

1. What Pepaxti is and what it is used for

Pepaxti belongs to a group of anticancer medicines called alkylating agents. It works by binding to DNA (the genetic instructions required for cell survival and multiplication) and damaging it, thereby helping to stop the growth of cancer cells.
Pepaxti is given together with the steroid dexamethasone for the treatment of adults with multiple myeloma, a type of blood cancer. It is used when the disease does not respond to at least three different types of anticancer medicines. If you have undergone a blood stem cell transplant (a procedure in which blood-forming cells are destroyed and replaced), the time interval from the transplant until the return of multiple myeloma must be at least 3 years.

2. What you need to know before you are given Pepaxti

Do not use Pepaxti

if you are allergic to melflufenamide or to any of the other ingredients of this medicine (listed in section 6).
if you are breastfeeding.

Warnings and precautions
Talk to your doctor or nurse before you are given Pepaxti.
Abnormal bleeding and bruising and low platelet count (blood cells)
Pepaxti may reduce the number of blood cells called platelets, which help blood to clot. Immediately inform your doctor or nurse if you start bleeding, e.g. nosebleeds, or develop bruises on your skin.
Fever and low white blood cell count
Pepaxti may reduce the number of white blood cells, which are important in fighting infections. Immediately inform your doctor or nurse if you experience 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 body's cells. Your doctor will regularly take blood samples to monitor your blood cells. Immediately inform your doctor or nurse if you feel weak or tired, if you are pale, or have shortness of breath.
Infections
Infections such as lung infection (pulmonary infection) and upper respiratory tract infection (causing cold-like symptoms) are very common with Pepaxti. Immediately inform your doctor or nurse if you develop 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
Inform your doctor if you experience diarrhea, nausea, or vomiting.
Risk of developing blood clots
The use of Pepaxti in combination with dexamethasone may increase the risk of developing blood clots. Inform your doctor or nurse if you have previously had a blood clot in a vein (thrombosis). Immediately inform your doctor or nurse if you develop swelling in an arm or leg, have difficulty breathing, or experience chest pain.
Risk of developing another cancer
It is important to remember that patients with multiple myeloma treated with Pepaxti may develop other types of cancer; therefore, your doctor must carefully evaluate the benefits and risks for you when prescribing this medicine.
Nephropathy
If you have reduced kidney function, the side effects of Pepaxti on blood cells may be more severe. There is insufficient information available on the use of this medicine in patients with severely reduced kidney function to recommend a safe and effective dose.
Vaccinations
Vaccines containing live but weakened organisms, called live attenuated vaccines (such as vaccines against measles, mumps, and rubella), must not be used during treatment with Pepaxti, as they may cause infection. However, some other types of vaccines, called inactivated vaccines or mRNA vaccines, may be used. Inform your healthcare provider that you are receiving treatment with Pepaxti before receiving any vaccination.
Children and adolescents
Pepaxti is not intended for use in children or adolescents under 18 years of age.
Other medicines and Pepaxti
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before receiving this medicine.
Pregnancy
The use of this medicine is not recommended during pregnancy unless absolutely necessary. Avoid becoming pregnant during treatment with this medicine, as it may harm the unborn baby. Your doctor will discuss with you the potential risks of using Pepaxti during pregnancy.
If you are a woman of childbearing potential:

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

If you are a man who could father a child:

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

Breastfeeding
You must not breastfeed during treatment with Pepaxti, as it may be harmful to the baby.
Fertility
Pepaxti may affect the ovaries or sperm, causing infertility (inability to have a child). In women, menstrual cycles may stop. In men, inability to father a child (sterility) due to absence of sperm may be permanent. Ask your doctor about sperm preservation before starting treatment.
Driving and using machines
Pepaxti may cause nausea and dizziness, which may impair your ability to drive or operate machinery.

3. How Pepaxti is administered

Pepaxti is reconstituted into a solution and administered by a doctor or nurse as an intravenous infusion (a drip into a vein) over 30 minutes. Your doctor will determine the correct dose of Pepaxti.
The recommended starting dose is 40 mg once every 4 weeks. If your body weight is equal to or less than 60 kg, the recommended starting dose is 30 mg once every 4 weeks. Treatment will continue as long as you benefit from it and do not experience unacceptable side effects. As part of your treatment, you will also take another medicine, dexamethasone, by mouth.
If you are given more Pepaxti than you should receive
This medicine will be administered by a doctor or nurse. In the unlikely event that you receive an excessive dose (overdose), your doctor will monitor you, including taking blood samples to monitor blood cells.
If you miss a dose of Pepaxti
It is very important to attend all your appointments to ensure that your treatment remains effective. 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 everyone gets them.
If you experience any of the following serious side effects, contact your doctor immediately
as urgent medical treatment may be required:

fever, chills, sore throat, cough or other signs of infection (due to lack of white blood cells called neutrophils that fight infections);
rapid breathing, fast pulse, fever and chills, little or no urination, nausea and vomiting, confusion, unconsciousness (due to a severe bacterial blood infection called sepsis or septic shock);
bleeding or bruising without obvious cause, including nosebleeds [due to a low number of platelets in the blood (thrombocytopenia)];
shortness of breath (due to severe chest infection, lung inflammation or blood clot in the lungs);
pain and swelling in the legs or arms, particularly in the lower leg or calves (caused by blood clots).

Other side effects that may occur
Very common (may affect more than 1 in 10 people):

reduced number of platelets (thrombocytopenia)
reduced number of a type of white blood cells called neutrophils (neutropenia)
reduced number of red blood cells carrying oxygen in the blood (anaemia), resulting in weakness and fatigue
lung infection (pulmonary infection)
respiratory tract infection presenting, for example, with fever, cough and cold-like symptoms
diarrhoea
nausea
fever
cough
shortness of breath
extreme tiredness
weakness

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

severe bacterial blood infection (sepsis)
fever associated with reduced number of white blood cells (neutropenia)
reduced number of a type of white blood cells called lymphocytes (lymphopenia), which also help fight infections
reduced overall number of white blood cells
reduced appetite
low potassium levels (may cause muscle weakness and irregular heartbeat)
high levels of uric acid in the blood (may cause gout and kidney problems)
headache
dizziness
shortness of breath during activity
nosebleeds
vomiting
deep vein thrombosis (blood clot in a vein)
bruising

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

severe bacterial blood infection with dangerously low blood pressure (septic shock) which may be life-threatening or even fatal
blood clot in the lungs
a type of blood cancer called myelodysplastic syndrome (MDS)
a type of blood cancer called acute myeloid leukaemia (AML).

Your doctor or nurse may give you additional medicines to treat symptoms and/or prevent side effects.
Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Pepaxti

Pepaxti will be stored at the hospital or clinic; therefore, 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 stated on the vial label and on the carton after “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. This will help protect the environment.

6. Package contents and other information

What Pepaxti contains

The active substance is melflufenamide. One vial contains 20 mg of melflufenamide (as hydrochloride).
The other ingredient is sucrose (sugar).

Description of the appearance of Pepaxti and contents of the pack
Pepaxti is a white to off-white powder contained in a glass vial.
Each carton 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
For further information on this medicinal product, please contact the Marketing Authorization Holder:
Oncopeptides AB (publ)
e-mail: [email protected]
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

The following information is intended exclusively for healthcare professionals:

Detailed instructions for use, handling, reconstitution, and administration
Pepaxti must be prepared by a healthcare professional using aseptic technique to ensure sterility of the prepared solution.
Additional solvents required for preparation
5% glucose solution for injection/infusion (at room temperature).
250 mL bag of 9 mg/mL (0.9%) sodium chloride injection solution, cold (2 °C – 8 °C, refrigerated for at least 4 hours) for injection.
Table 1. Dilution volumes for Pepaxti dose

Description of volume	Pepaxti dose
Description of volume	40 mg (2 vials)	30 mg (1.5 vials)	20 mg (1 vial)	15 mg (0.75 vial)
Volume of reconstituted Pepaxti solution required for final product	80 mL	60 mL	40 mL	30 mL
Total final volume of infusion bag after dilution	250 mL	230 mL	210 mL	200 mL
Concentration of Pepaxti after dilution	0.16 mg/mL	0.13 mg/mL	0.10 mg/mL	0.08 mg/mL

Preparation steps
Read the instructions in full before starting preparation.
Steps 3 to 5 must be completed within 30 minutes.
Reconstitution and dilution steps
Step 1
Determine the number of vials required for the dose, according to Table 1 “Dilution volumes for
Pepaxti dose”. Allow the vial or vials to stand at room temperature for at least
30 minutes.
Step 2
Vigorously shake or vortex the vial or vials to break up the lyophilized powder aggregate into loose powder.
Steps 3 to 5 must be completed within 30 minutes.
Step 3

For a 40 mg dose of Pepaxti	For a 30 mg dose of Pepaxti	For a 20 mg dose of Pepaxti	For a 15 mg dose of Pepaxti
Reconstitute under aseptic conditions	Reconstitute under aseptic conditions	Reconstitute under aseptic conditions	Reconstitute under aseptic conditions
each of the 2 vials with 40 mL of 5% glucose solution for infusion to obtain a final concentration of 0.5 mg/mL.	each of the 2 vials with 40 mL of 5% glucose solution for infusion to obtain a final concentration of 0.5 mg/mL.	1 vial with 40 mL of 5% glucose solution for infusion to obtain a final concentration of 0.5 mg/mL.	1 vial with 40 mL of 5% glucose solution for infusion to obtain a final concentration of 0.5 mg/mL.

Ensure that the 5% glucose solution for infusion is at room temperature (20 °C – 25 °C). Shake the vial or vials vigorously until a clear solution is obtained.
Allow the vial or vials to stand to enable dispersion of air bubbles and check that the solution is clear.
Step 4
Withdraw 80 mL from a refrigerated (2 °C – 8 °C) 250 mL bag of sodium chloride 9 mg/mL (0.9%) injection solution. Discard the 80 mL withdrawn.
Step 5

For a 40 mg dose of Pepaxti	For a 30 mg dose of Pepaxti	For a 20 mg dose of Pepaxti	For a 15 mg dose of Pepaxti
Withdraw 80 mL of reconstituted solution from the Pepaxti vials and transfer it into an intravenous (i.v.) infusion solution containing sodium chloride 9 mg/mL (0.9%) to achieve a final concentration of 0.16 mg/mL.	Withdraw 60 mL of reconstituted solution from the Pepaxti vials and transfer it into an intravenous (i.v.) infusion solution containing sodium chloride 9 mg/mL (0.9%) to achieve a final concentration of 0.13 mg/mL.	Withdraw 40 mL of reconstituted solution from the Pepaxti vial and transfer it into an intravenous (i.v.) infusion solution containing sodium chloride 9 mg/mL (0.9%) to achieve a final concentration of 0.10 mg/mL.	Withdraw 30 mL of reconstituted solution from the Pepaxti vial and transfer it into an intravenous (i.v.) infusion solution containing sodium chloride 9 mg/mL (0.9%) to achieve a final concentration of 0.08 mg/mL.

Discard any unused portions remaining in the vial or vials.
Gently invert the infusion bag to mix the solution. Do not shake. Check that the solution is from clear and colourless to pale yellow. Do not use if a change in colour of the solution or presence of particles is observed.
Storage times
Pepaxti degrades in solution, especially at room temperature. Do not exceed the prescribed storage times for the diluted solution.
For immediate administration
The infusion of the diluted solution must be started within 60 minutes of the start of reconstitution (step 3).
In case of delayed administration
If not used immediately for administration, the diluted solution must be placed in a refrigerator (2 °C – 8 °C) within 30 minutes after initial reconstitution (step 3) and stored for a maximum of 6 hours.
Administration
Parenteral medicinal products should be inspected visually before administration to ensure there is no particulate matter or discoloration. Do not use if opaque particles, colour change or foreign particles are observed.
Steps of administration
Step 6
Administer Pepaxti by a 30-minute intravenous infusion through a peripheral vein or via a central venous access device, such as a PICC or tunneled central venous catheter. If the infusion bag has been stored in the refrigerator, allow it to reach room temperature (20 °C – 25 °C). Begin infusion within 30 minutes after removing the diluted solution from the refrigerator.
Step 7
After completion of the Pepaxti infusion, flush the catheter with a 9 mg/mL (0.9%) sodium chloride injection solution.
Disposal
Pepaxti is a cytotoxic medicinal product intended for single use only. Healthcare workers or medical personnel must follow procedures for the safe handling and disposal of nitrogen mustard analogues, in accordance with current recommendations for cytotoxic medicinal products. Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.