Tepkinly: detailed information

Patient Information Leaflet

Tepkinly 4 mg/0.8 mL solution for injection

epcoritamab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will provide you with a Patient Alert Card. Read it carefully and follow the instructions contained therein. Always keep the Patient Alert Card with you.
Always show the Patient Alert Card to your doctor or nurse when you see them, or when you go to hospital.
If you have any questions, ask your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Tepkinly is and what it is used for

What Tepkinly is
Tepkinly is an antitumor medicinal product containing the active substance epcoritamab. Tepkinly is used
alone (monotherapy) to treat adult patients with a blood cancer called
diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) when the disease has
recurred or did not respond to prior treatment, and after at least two previous therapies.

How Tepkinly works
Epcoritamab is specifically designed to help the human immune system attack cancer cells (lymphoma). Epcoritamab works by binding to both immune cells and cancer cells in the body, bringing them together so that the immune system can destroy the cancer cells.

2. What you should know before using Tepkinly

Do not use Tepkinly
If you are allergic to epcoritamab or to any of the other ingredients of this medicine (listed in
section 6).
If you have any doubts, consult your doctor or nurse before being administered Tepkinly.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Tepkinly if:

You currently have or have previously had nervous system problems, such as seizures
You have an infection
You need to be vaccinated or know that you might need vaccination in the near future

If any of the above conditions apply to you (or if you are unsure), consult your doctor or
nurse before receiving Tepkinly.
Immediately inform your doctor if you experience symptoms of any of the following
adverse effects during or after treatment with Tepkinly. Further medical treatment may be
required.

Cytokine release syndrome (CRS) – a potentially life-threatening condition causing fever, vomiting, difficulty breathing/shortness of breath, chills, rapid heartbeat, headache, dizziness, or mild confusion, associated with medicines that stimulate T-cells.
Before each subcutaneous injection, you may be given medicines to help reduce the possible effects of cytokine release syndrome.
Hemophagocytic lymphohistiocytosis (HLH) – a rare condition in which the immune system produces too many normal infection-fighting cells called histiocytes and lymphocytes. It may cause enlargement of the liver and/or spleen, heart problems, and kidney abnormalities. Symptoms may include fever, rash, swollen lymph nodes, difficulty breathing, and easy bruising. Immediately inform your doctor if you experience these symptoms simultaneously.
ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome) – symptoms may include problems with language use (including speaking, understanding, writing, and reading), drowsiness, confusion/disorientation, muscle weakness, seizures, brain swelling, and memory loss.
Infections – you may develop signs of infection, such as fever of 38 °C or higher, chills, cough, or pain when urinating, which may vary depending on the site of infection.
Progressive multifocal leukoencephalopathy (PML) – symptoms of this serious and potentially fatal brain condition may include blurred vision, loss of vision, or double vision, difficulty speaking, weakness or clumsiness in an arm or leg, changes in walking or balance problems, personality changes, and changes in thinking, memory, and orientation leading to confusion. These symptoms may begin several months after treatment ends and usually develop slowly and gradually over weeks or months. It is important that your family members or caregivers are also aware of these symptoms, as they may notice symptoms you are not aware of.
Tumor lysis syndrome (TLS) – during treatment, some people may develop abnormal levels of certain salts in the blood due to the rapid breakdown of cancer cells. This is called tumor lysis syndrome (TLS). Your doctor or nurse will perform blood tests to monitor for this condition. Before each subcutaneous injection, you must be well hydrated and may receive other medicines to help lower high levels of uric acid and reduce the possible effects of tumor lysis syndrome.
Tumour flare – when cancer cells are destroyed, there may be a reaction that gives the impression of worsening disease—this is called a "tumour flare" reaction.

Children and adolescents
Tepkinly is not recommended for children and adolescents under 18 years of age, as there is
no information on its use in this age group.

Other medicines and Tepkinly
Inform your doctor or pharmacist if you are taking, have recently taken, or might take or use
any other medicines. This includes medicines obtained without a prescription and herbal
medicines.

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your
doctor or pharmacist before taking this medicine. Do not use Tepkinly during pregnancy, as
it may affect the unborn child. Before starting treatment, your doctor may ask you to take a
pregnancy test.

Contraception
Women of childbearing potential must use effective contraceptive methods to avoid
pregnancy during treatment with Tepkinly and for at least 4 months after the last dose of
Tepkinly. If you become pregnant during this period, inform your doctor immediately.
Discuss appropriate contraceptive methods with your doctor or nurse.

Breast-feeding
You must not breast-feed during treatment with Tepkinly and for at least 4 months after the
last dose. It is not known whether Tepkinly passes into breast milk and whether it could
affect the baby.

Fertility
The effect of Tepkinly on male and female fertility is unknown.

Driving and using machines
Due to the possible symptoms of ICANS, you should exercise caution when driving, riding a
bicycle, or operating heavy or potentially dangerous machinery. If you currently have such
symptoms, avoid these activities and contact your doctor, nurse, or pharmacist. See section 4
for more information on adverse effects.

Tepkinly contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., it is essentially
‘sodium-free’.

Tepkinly contains sorbitol
This medicine contains 21.9 mg of sorbitol per vial, equivalent to 27.33 mg/mL.

Tepkinly contains polysorbate
This medicine contains 0.42 mg of polysorbate 80 per vial, equivalent to 0.4 mg/mL.
Polysorbate 80 may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Tepkinly is administered

A doctor experienced in cancer treatment will manage your therapy. Follow the treatment schedule explained to you by your doctor.
Tepkinly will be administered to you by a doctor or nurse via a subcutaneous injection.
Tepkinly will be given in 28-day cycles, according to the dosage schedule prescribed by your doctor.
You will receive Tepkinly according to the following schedule:

Cycle	Dosing schedule
Cycles 1 to 3	Weekly
Cycles 4 to 9	Every two weeks
Cycle 10 and onwards	Every four weeks

Before receiving Tepkinly, you may be given other medicines to help prevent reactions such as cytokine release syndrome and fever during Cycle 1 (and potentially in future cycles).
These medicines may include:

Corticosteroids, such as dexamethasone, prednisolone, or equivalent
An antihistamine, such as diphenhydramine
Paracetamol

During the first month (Cycle 1) of treatment with Tepkinly:

It is important to stay well hydrated. For this reason, your doctor may ask you to drink plenty of water the day before and the day after receiving Tepkinly. On the day you receive Tepkinly, your doctor may administer fluids through a needle inserted into a vein (intravenously).
If you are taking medicine for high blood pressure, your doctor may ask you to temporarily stop taking it during treatment with Tepkinly.

If you have diffuse large B-cell lymphoma (DLBCL)
The first full dose (48 mg) of Tepkinly will be administered on Day 15 of Cycle 1. Your doctor will monitor the effects of the treatment and will ask you to remain in the hospital for 24 hours after the first full dose (48 mg), as reactions such as CRS, ICANS, and fever are more likely to occur during this period.

If you have follicular lymphoma (FL)
The first full dose (48 mg) of Tepkinly will be administered on Day 22 of Cycle 1.
You will continue receiving Tepkinly for as long as your doctor considers that you are benefiting from the treatment.
Your doctor may delay or permanently discontinue treatment with Tepkinly if you experience certain side effects.

If you forget to use Tepkinly
If you miss or forget a medical appointment, schedule another one immediately. To ensure the treatment is fully effective, it is very important not to miss any doses.

If you stop treatment with Tepkinly
Do not stop treatment with Tepkinly unless you have discussed it with your doctor. Stopping treatment may worsen your condition.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Serious side effects
Inform your doctor immediately if you notice any of the symptoms of the serious side effects listed below. You may experience only one or some of these symptoms.
Cytokine release syndrome (CRS) (very common: may affect more than 1 in 10 people)
Symptoms may include

fever
vomiting
dizziness or mild confusion
chills
rapid heartbeat
difficulty breathing / shortness of breath
headache

Immune effector cell-associated neurotoxicity syndrome (ICANS) (common: may affect up to 1 in 10 people)

effects on the nervous system, whose symptoms may appear days or weeks after injection and may initially be subtle. Some of these symptoms could be signs of a serious immune reaction called "immune effector cell-associated neurotoxicity syndrome" (ICANS). Symptoms may include
difficulty speaking or writing
drowsiness
confusion/disorientation
muscle weakness
seizures
memory loss

Tumour lysis syndrome (TLS) ( common: may affect up to 1 in 10 people)
Symptoms may include

fever
chills
vomiting
confusion
shortness of breath
seizures
irregular heartbeat
dark or cloudy urine
unusual tiredness
muscle or joint pain

Haemophagocytic lymphohistiocytosis (HLH) ( uncommon: may affect up to 1 in 100 people)

a condition in which the immune system produces excessive numbers of certain cells normally involved in fighting infections, called histiocytes and lymphocytes. Symptoms may include
fever
rash
swollen lymph nodes
difficulty breathing
easy bruising

Other side effects
Inform your doctor or nurse immediately if you experience any of the side effects listed below or if they worsen:
Very common: may affect more than 1 in 10 people

viral infection
pneumonia (lung infection)
upper respiratory tract infections (airway infections)
reduced appetite
pain in bones, joints, ligaments, and muscles
abdominal pain
headache
nausea
diarrhoea
rash
fatigue
injection site reactions
fever
swelling

Detected in blood tests

low levels of a type of white blood cells that fight infections (neutropenia)
low levels of red blood cells, which may cause fatigue, pale skin, and shortness of breath (anaemia)
low levels of platelets, which may lead to bleeding and bruising (thrombocytopenia)
reduced levels of a type of white blood cells called lymphocytes, which may affect the body's ability to fight infections (lymphopenia)

Common: may affect up to 1 in 10 people

fever due to infection in the presence of low white blood cell counts (febrile neutropenia)
swollen and painful lymph nodes, chest pain, cough or difficulty breathing, pain at tumour site ( tumour flare )
fungal infections (caused by an organism called fungus)
skin infections
life-threatening reaction of the body to an infection (sepsis)
rapid breakdown of tumour cells leading to chemical changes in the blood and organ damage, including to kidneys, heart, and liver (tumour lysis syndrome)
irregular heartbeat
excess fluid around the lungs which may make breathing difficult (pleural effusion)
vomiting
itching sensation (pruritus)

Detected in blood tests

low levels of phosphate, potassium, magnesium, or sodium in the blood
increased levels of creatinine in the blood, a breakdown product of muscle tissue
increased levels of liver proteins in the blood, which may indicate liver problems

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tepkinly

Tepkinly will be stored by the doctor, nurse, or pharmacist at the hospital or clinic.
To store Tepkinly correctly

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 after EXP and on the packaging after Exp. The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C–8 °C).
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Tepkinly 4 mg/0.8 mL is a solution that may be diluted prior to use.
Dilute prior to subcutaneous use for the 0.16 mg and 0.8 mg doses.
No dilution is required for the 3 mg dose.
If not used immediately, the prepared solution can be stored for up to 24 hours at 2–8 °C from the time of preparation.
Within these 24 hours, the prepared solution may be kept for a maximum of 12 hours at room temperature (20 °C–25 °C) from the start of dose preparation.
Allow the solution to reach room temperature before use.

The doctor, nurse, or pharmacist will dispose of any unused medicine in accordance with
local regulations. This will help protect the environment.

6. Package contents and other information

What Tepkinly contains

The active substance is epcoritamab. Each 0.8 mL vial contains 4 mg of epcoritamab at a concentration of 5 mg/mL.
The other ingredients are sodium acetate trihydrate, acetic acid, sorbitol (E420), polysorbate 80, and water for injections (see section 2 “Tepkinly contains sodium”, “Tepkinly contains sorbitol”, and “Tepkinly contains polysorbate 80”).

Description of the appearance of Tepkinly and contents of the pack
Tepkinly is an injectable solution. It is a solution ranging from colourless to slightly yellowish, supplied in a glass vial.
Each pack contains 1 vial.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie S.r.l.
S.R. 148 Pontina, km 52 SNC
04011 Campoverde di Aprilia (LT)
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel: +385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

This medicinal product has been granted a marketing authorisation under “conditional approval”. This means that additional data on this medicinal product are required.
The European Medicines Agency will review new information on this medicinal product at least annually, and this package leaflet will be updated if necessary.

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
The latest approved versions of the package leaflet and patient information leaflet for this medicinal product are available by scanning the QR code printed on this leaflet and on the outer carton with a smartphone or device. The same information is also available at the following URL:
www.tepkinly.eu
QR code to be included

To listen to or request a copy of this leaflet in , or ,
please contact the local representative of the Marketing Authorisation Holder.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

The following information is intended exclusively for healthcare professionals:

Read this entire section carefully before preparing epcoritamab. Determine
doses (the initial dose (0.16 mg) and the intermediate dose (0.8 mg)) of epcoritamab require dilution
before administration. Follow all preparation instructions below, as incorrect preparation may result in an incorrect dose. Epcoritamab can be diluted using two different methods: the vial method or the syringe method.
Epcoritamab is prepared and administered as a subcutaneous injection.
Each epcoritamab vial is for single use only.
Each vial contains an overage to allow withdrawal of the indicated nominal amount.
Epcoritamab must be diluted and administered by a healthcare professional using aseptic technique.
Filtration of the diluted solution is not required.
Epcoritamab should be inspected visually prior to administration for particulate matter and discoloration. The injectable solution should be a clear, colorless to slightly yellow solution. Do not use if the solution shows discoloration, is cloudy, or contains foreign particles.

Preparation of diluted epcoritamab using the empty sterile vial method

Instructions for preparing the initial 0.16 mg dose – 2 dilutions required – empty sterile vial method
Use a syringe, vial, and needle of appropriate size for each transfer step.

Prepare the Tepkinly vial
a) Remove one 4 mg/0.8 mL Tepkinly vial with a blue cap from the refrigerator.
b) Allow the vial to reach room temperature for no more than 1 hour.
c) Gently swirl the Tepkinly vial.
DO NOT vortex or shake vigorously.
Perform the first dilution
a) Label an appropriately sized empty vial as “dilution A”.
b) Transfer 0.8 mL of Tepkinly into the dilution A vial.
c) Transfer 4.2 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution A vial. The initial diluted solution contains 0.8 mg/mL of epcoritamab.
d) Gently swirl the dilution A vial for 30–45 seconds.
Perform the second dilution
a) Label an appropriately sized empty vial as “dilution B”.
b) Transfer 2 mL of solution from the dilution A vial into the dilution B vial. The dilution A vial is no longer needed and must be discarded.
c) Transfer 8 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution B vial to obtain a final concentration of 0.16 mg/mL.
d) Gently swirl the dilution B vial for 30–45 seconds.
Withdraw the dose
Withdraw 1 mL of diluted epcoritamab from the dilution B vial using a syringe. The dilution B vial is no longer needed and must be discarded.
Label the syringe
Label the syringe with the name of the medicinal product, dosage (0.16 mg), date, and time of day.
Dispose of the vial and any unused portion of Tepkinly in accordance with local regulations.

Instructions for preparing the intermediate 0.8 mg dose – 1 dilution required – empty sterile vial method
Use a syringe, vial, and needle of appropriate size for each transfer step.

Prepare the Tepkinly vial
a) Remove one 4 mg/0.8 mL Tepkinly vial with a blue cap from the refrigerator.
b) Allow the vial to reach room temperature for no more than 1 hour.
c) Gently swirl the Tepkinly vial.
DO NOT vortex or shake vigorously.
Perform the dilution
a) Label an appropriately sized empty vial as “dilution A”.
b) Transfer 0.8 mL of Tepkinly into the dilution A vial.
c) Transfer 4.2 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution A vial to obtain a final concentration of 0.8 mg/mL.
d) Gently swirl the dilution A vial for 30–45 seconds.
Withdraw the dose
Withdraw 1.0 mL of diluted epcoritamab from the dilution A vial using a syringe. The dilution A vial is no longer needed and must be discarded.
Label the syringe
Label the syringe with the name of the medicinal product, dosage (0.8 mg), date, and time of day.
Dispose of the vial and any unused portion of Tepkinly in accordance with local requirements.

Preparation of diluted epcoritamab using the sterile syringe method

Instructions for preparing the initial 0.16 mg dose – 2 dilutions required – sterile syringe method
Use a syringe and needle of appropriate size for each transfer step.

Prepare the epcoritamab vial
a) Remove one 4 mg/0.8 mL epcoritamab vial with a blue cap from the refrigerator.
b) Allow the vial to reach room temperature for no more than 1 hour.
c) Gently swirl the epcoritamab vial.
DO NOT vortex or shake vigorously.
Perform the first dilution
a) Label an appropriately sized syringe as “dilution A”.
b) Draw 4.2 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution A syringe. Include approximately 0.2 mL of air in the syringe.
c) Using a new syringe labeled “syringe 1”, withdraw 0.8 mL of epcoritamab.
d) Connect the two syringes and transfer the 0.8 mL of epcoritamab into the dilution A syringe. The initially diluted solution contains 0.8 mg/mL of epcoritamab.
e) Gently mix by inverting the connected syringes 180 degrees five times.
f) Disconnect the syringes and discard syringe 1.
Perform the second dilution
a) Label an appropriately sized syringe as “dilution B”.
b) Draw 8 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution B syringe. Include approximately 0.2 mL of air in the syringe.
c) Label another appropriately sized syringe as “syringe 2”.
d) Connect syringe 2 to the dilution A syringe and transfer 2 mL of solution into syringe 2. The dilution A syringe is no longer needed and must be discarded.
e) Connect syringe 2 to the dilution B syringe and transfer 2 mL of solution into the dilution B syringe to obtain a final concentration of 0.16 mg/mL.
f) Gently mix by inverting the connected syringes 180 degrees five times.
g) Disconnect the syringes and discard syringe 2.
Withdraw the dose
Connect a new syringe to the dilution B syringe and transfer 1 mL of diluted epcoritamab from the dilution B syringe into the new syringe. The dilution B syringe is no longer needed and must be discarded.
Label the syringe
Label the syringe with the name of the medicinal product, dosage (0.16 mg), date, and time of day.
Dispose of the vial and any unused portion of Tepkinly in accordance with local regulations.

Instructions for preparing the intermediate 0.8 mg dose – 1 dilution required – sterile syringe method
Use a syringe and needle of appropriate size for each transfer step.

Prepare the Tepkinly vial
a) Remove one 4 mg/0.8 mL Tepkinly vial with a blue cap from the refrigerator.
b) Allow the vial to reach room temperature for no more than 1 hour.
c) Gently swirl the Tepkinly vial.
DO NOT vortex or shake vigorously.
Perform the dilution
a) Label an appropriately sized syringe as “dilution A”.
b) Draw 4.2 mL of sterile sodium chloride solution 9 mg/mL (0.9%) into the dilution A syringe. Include approximately 0.2 mL of air in the syringe.
c) Using a new syringe labeled “syringe 1”, withdraw 0.8 mL of epcoritamab.
d) Connect the two syringes and transfer the 0.8 mL of epcoritamab into the dilution A syringe to obtain a final concentration of 0.8 mg/mL.
e) Gently mix by inverting the connected syringes 180 degrees five times.
f) Disconnect the syringes and discard syringe 1.
Withdraw the dose
Connect a new syringe to the dilution A syringe and transfer 1 mL of diluted epcoritamab into the new syringe. The dilution A syringe is no longer needed and must be discarded.
Label the syringe
Label the syringe with the name of the medicinal product, dosage (0.8 mg), date, and time of day.
Dispose of the vial and any unused portion of Tepkinly in accordance with local regulations.

Preparation of the 3 mg epcoritamab dose

Instructions for preparing the second intermediate 3 mg dose (No dilution required)
The 3 mg dose of epcoritamab is required only for patients with FL.

Prepare the Tepkinly vial
a) Remove one 4 mg/0.8 mL Tepkinly vial with a blue cap from the refrigerator.
b) Allow the vial to reach room temperature for no more than 1 hour.
c) Gently swirl the Tepkinly vial.
DO NOT vortex or shake vigorously.
Withdraw the dose
Withdraw 0.6 mL of epcoritamab and transfer it into a syringe.
Label the syringe
Label the syringe with the dosage (3 mg), date, and time of day.
Dispose of the vial and any unused portion of Tepkinly in accordance with local regulations.

Traceability
To improve traceability of biological medicinal products, the name and batch number of the administered product must be clearly documented.

Patient information leaflet

Tepkinly 48 mg solution for injection

epcoritamab
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicinal product. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicinal product as it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will provide you with a Patient Card. Read it carefully and follow the instructions contained therein. Always carry your Patient Card with you.
Always show your Patient Card to your doctor or nurse when you see them, or when you go to hospital.
If you have any questions, consult your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Tepkinly is and what it is used for

What Tepkinly is
Tepkinly is an anticancer medicine that contains the active substance epcoritamab. Tepkinly is used
alone (monotherapy) to treat adult patients with a blood cancer called
diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) when the disease has relapsed or
has not responded to prior treatment after at least two previous therapies.
How Tepkinly works
Epcoritamab is specifically designed to help the human immune system attack cancer cells (lymphoma). Epcoritamab works by binding to both immune cells and cancer cells in the body, bringing them together so that the immune system can destroy the cancer cells.

2. What you need to know before using Tepkinly

Do not use Tepkinly
If you are allergic to epcoritamab or to any of the other ingredients of this medicine (listed in
section 6).
If you are unsure, consult your doctor or nurse before being administered Tepkinly.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Tepkinly if:

you currently have or have previously had neurological problems, such as seizures
you have an infection
you need to be vaccinated or know that you may need vaccination in the near future.

If any of the above conditions apply to you (or if you are unsure), consult your doctor or
nurse before receiving Tepkinly.
Immediately inform your doctor if you experience symptoms of any of the following adverse
reactions during or after treatment with Tepkinly. Additional medical treatment may be
required.

Cytokine release syndrome (CRS) – a life-threatening condition causing fever, vomiting, difficulty breathing/shortness of breath, chills, rapid heartbeat, headache, dizziness, or mild confusion, associated with medicines that stimulate T cells.
Before each subcutaneous injection, you may be given medications to help reduce the potential effects of cytokine release syndrome.
Haemophagocytic lymphohistiocytosis (HLH) – a rare condition in which the immune system produces excessive numbers of certain cells normally involved in fighting infections, called histiocytes and lymphocytes. It may cause enlargement of the liver and/or spleen, heart problems, and kidney abnormalities. Symptoms may include fever, rash, swollen lymph nodes, difficulty breathing, and easy bruising. Inform your doctor immediately if you experience these symptoms simultaneously.
Immune effector cell-associated neurotoxicity syndrome (ICANS) – symptoms may include problems with language use (including speaking, understanding, writing, and reading), drowsiness, confusion/disorientation, muscle weakness, seizures, brain swelling, and memory loss.
Infections – you may experience signs of infection, such as fever of 38°C or higher, chills, cough, or pain when urinating, which may vary depending on the site of infection.
Progressive multifocal leukoencephalopathy (PML) – symptoms of this serious and potentially fatal brain condition may include blurred vision, vision loss or double vision, difficulty speaking, weakness or clumsiness in an arm or leg, changes in walking or balance problems, personality changes, and changes in thinking, memory, and orientation leading to confusion. These symptoms may begin several months after treatment ends and usually develop slowly and gradually over weeks or months. It is important that your family members or caregivers are also aware of these symptoms, as they may notice signs you are not aware of.
Tumour lysis syndrome (TLS) during treatment – in some people, unusual levels of certain salts in the blood may occur due to the rapid breakdown of cancer cells. This is known as tumour lysis syndrome (TLS). Your doctor or nurse will perform blood tests to monitor for this condition. Before each subcutaneous injection, you must be well hydrated and may receive additional medications to help lower high levels of uric acid and reduce the potential effects of tumour lysis syndrome.
Tumour flare reaction – when cancer cells are destroyed, they may react in a way that appears to worsen the disease—this is known as a “tumour flare reaction.”

Children and adolescents
Tepkinly is not recommended for children and adolescents under 18 years of age, as there is no
information available on its use in this age group.
Other medicines and Tepkinly
Inform your doctor or pharmacist if you are currently taking or using, have recently taken or used, or
might take or use any other medicines. This includes medicines obtained without a prescription and
herbal remedies.
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your
doctor or pharmacist before taking this medicine. Do not use Tepkinly during pregnancy, as it may
affect the unborn baby. Before starting treatment, your doctor may ask you to undergo a pregnancy
test.
Contraception
Women of childbearing potential must use effective contraceptive measures to prevent pregnancy
during treatment with Tepkinly and for at least 4 months after the last dose of Tepkinly. If you become
pregnant during this period, inform your doctor immediately. Discuss appropriate contraceptive
measures with your doctor or nurse.
Breast-feeding
You must not breast-feed during treatment with Tepkinly and for at least 4 months after the last dose.
It is not known whether Tepkinly passes into breast milk or if it may affect the breast-fed infant.
Fertility
The effect of Tepkinly on male and female fertility is unknown.
Driving and using machines
Due to the possible symptoms of ICANS, you should exercise caution when driving, cycling, or
operating heavy or potentially dangerous machinery. If you currently have such symptoms, avoid
these activities and contact your doctor, nurse, or pharmacist. See section 4 for more information on
adverse reactions.
Tepkinly contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially ‘sodium-free’.
Tepkinly contains sorbitol
This medicine contains 21.9 mg of sorbitol per vial, equivalent to 27.33 mg/mL.
Tepkinly contains polysorbate
This medicine contains 0.42 mg of polysorbate 80 per vial, equivalent to 0.4 mg/mL. Polysorbate 80
may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Tepkinly is administered

A doctor experienced in cancer treatment will manage your therapy. Follow the treatment schedule explained to you by your doctor.
Tepkinly will be administered to you by a doctor or nurse through a subcutaneous injection.
Tepkinly will be given in 28-day cycles, according to the dosage schedule prescribed by your doctor.
You will be administered Tepkinly according to the following schedule:

Cycle	Dosing schedule
Cycles 1 to 3	Weekly
Cycles 4 to 9	Every two weeks
Cycle 10 and onwards	Every four weeks

Before receiving Tepkinly, you may be given other medicines. This is to help prevent reactions such as cytokine release syndrome and fever during Cycle 1 (and potentially in future cycles).
These medicines may include:

Corticosteroids, such as dexamethasone, prednisolone or equivalent
An antihistamine, such as diphenhydramine
Paracetamol

During the first month (Cycle 1) of treatment with Tepkinly:

It is important to stay well hydrated. For this reason, your doctor may ask you to drink plenty of water the day before and the day after receiving Tepkinly. On the day you receive Tepkinly, your doctor may give you fluids through a needle inserted into a vein (intravenously).
If you are taking a medicine for high blood pressure, your doctor may ask you to stop taking it for a short period during treatment with Tepkinly.

If you have diffuse large B-cell lymphoma (DLBCL)
Your first full dose (48 mg) of Tepkinly will be given on Day 15 of Cycle 1. Your doctor will monitor the effects of the treatment and will ask you to remain in hospital for 24 hours after the first full dose (48 mg), as reactions such as CRS, ICANS and fever are more likely during this period.

If you have follicular lymphoma (FL)
Your first full dose (48 mg) of Tepkinly will be given on Day 22 of Cycle 1.
You will continue to receive Tepkinly for as long as your doctor considers that you are benefiting from the treatment.
Your doctor may delay or permanently stop treatment with Tepkinly if you experience certain side effects.

If you forget to use Tepkinly
If you miss or forget a medical appointment, schedule another one immediately. It is very important not to miss any doses to ensure the treatment is fully effective.

If you stop treatment with Tepkinly
Do not stop treatment with Tepkinly unless you have discussed it with your doctor. Stopping treatment may worsen your condition.

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

4. Possible side effects

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

Serious side effects
Contact your doctor immediately if you notice any of the symptoms of the serious side effects listed below. You may experience only one or some of these symptoms.

Cytokine release syndrome (CRS) (very common: may affect more than 1 in 10 people)
Symptoms may include:

fever
vomiting
dizziness or mild confusion
chills
rapid heartbeat
difficulty breathing / shortness of breath
headache

Immune effector cell-associated neurotoxicity syndrome (ICANS) (common: may affect up to 1 in 10 people)

effects on the nervous system, whose symptoms may appear days or weeks after injection and may initially be subtle. Some of these symptoms could be signs of a serious immune reaction called "immune effector cell-associated neurotoxicity syndrome" (ICANS). Symptoms may include:
difficulty speaking or writing
drowsiness
confusion/disorientation
muscle weakness
seizures
memory loss

Tumour lysis syndrome (TLS) (common: may affect up to 1 in 10 people)
Symptoms may include:

fever
chills
vomiting
confusion
shortness of breath
seizures
irregular heartbeat
dark or cloudy urine
unusual tiredness
muscle or joint pain

Haemophagocytic lymphohistiocytosis (HLH) (uncommon: may affect up to 1 in 100 people)

a condition in which the immune system produces excessive numbers of certain defence cells normally involved in fighting infections, called histiocytes and lymphocytes. Symptoms may include:
fever
rash
swollen lymph nodes
difficulty breathing
easy bruising

Other side effects
Contact your doctor or nurse immediately if you experience any of the side effects listed below or if they worsen:

Very common: may affect more than 1 in 10 people

viral infection
pneumonia (lung infection)
upper respiratory tract infections (airway infections)
reduced appetite
pain in bones, joints, ligaments, and muscles
abdominal pain
headache
nausea
diarrhoea
rash
fatigue
injection site reactions
fever
swelling

Detected in blood tests:

low levels of a type of white blood cells that fight infections (neutropenia)
low levels of red blood cells, which may cause fatigue, pale skin, and shortness of breath (anaemia)
low levels of platelets, which may lead to bleeding and bruising (thrombocytopenia)
reduced levels of a type of white blood cells called lymphocytes, which may affect the body’s ability to fight infections (lymphopenia)