Tepkinly 4 mg/0.8 ml solution for injection: detailed information

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

Tepkinly 4 mg/0.8 ml solution for injection

epcoritamab

This medicinal product is subject to additional monitoring, which will allow for faster identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet includes information on how to report adverse reactions.

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

Keep this leaflet, as you may need to read it again.
Your doctor will provide you with a patient information card. Read it carefully and follow the instructions it contains. Always carry this patient information card with you.
Always show the patient information card to your doctor, nurse, or if you visit a hospital.
If you have any questions, consult your doctor, pharmacist, or nurse.
If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are possible adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

What Tepkinly is and what it is used for
What you need to know before using Tepkinly
How to use Tepkinly
Possible adverse 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 a cancer medicine that contains the active substance epcoritamab. Tepkinly is used alone (monotherapy) to treat adult patients who have a type of blood cancer called diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) when the disease has returned or has not responded to prior treatment after at least two previous therapies.

How Tepkinly works

Epcoritamab is specifically designed to help your own immune system attack cancer cells (lymphoma). Epcoritamab works by binding to immune cells and cancer cells in your body, bringing them together so that your 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 in doubt, consult your doctor or nurse before receiving Tepkinly.

Warnings and precautions

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

you have or have had problems with your nervous system, such as seizures
you have an infection
you are due to receive a vaccine or know you will need one in the near future.

If any of the above apply to you (or you are unsure), consult your doctor or nurse before receiving Tepkinly.

Your doctor or nurse will perform blood tests before and during treatment with epcoritamab to monitor your antibody levels and assess your risk of infection, as well as determine whether you need specific treatment.

Immediately inform your doctor if you experience symptoms of any of the following adverse effects listed below during or after treatment with Tepkinly. You may require additional medical treatment.

Cytokine release syndrome (CRS): a potentially life-threatening condition causing fever, vomiting, difficulty breathing/shortness of breath, chills, rapid heartbeat, headache, and dizziness or mild lightheadedness, associated with medications that stimulate T cells.

_Before each subcutaneous injection, you may be given medications to help reduce the potential effects of cytokine release syndrome.

Hemophagocytic lymphohistiocytosis (HLH): a rare condition in which the immune system produces excessive numbers of otherwise normal infection-fighting cells called histiocytes and lymphocytes. This may cause enlargement of the liver and/or spleen, heart problems, and kidney abnormalities. Symptoms may include fever, rash, swollen lymph nodes, breathing difficulties, and easy bruising. Immediately inform your doctor 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, 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 disturbances in thinking, memory, and orientation leading to confusion. These symptoms may begin several months after treatment has ended and usually develop slowly and progressively 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 do not.
Tumor lysis syndrome (TLS): some people may develop abnormal levels of certain salts in the blood due to the rapid breakdown of cancer cells during treatment. This is known as tumor lysis syndrome (TLS).
Your doctor or nurse will perform blood tests to check for this condition. Before each subcutaneous injection, you must be well hydrated, and you may be given other medications to help reduce elevated uric acid levels and minimize the potential effects of tumor lysis syndrome.
Tumor flare reaction: as your cancer is destroyed, you may experience a reaction that appears to worsen your condition—this is called a "tumor 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 taking, have recently taken, or might need to take any other medicines. This includes over-the-counter medicines and herbal remedies.

Pregnancy

If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Do not use Tepkinly during pregnancy, as it may harm the fetus. Your doctor may ask you to take a pregnancy test before starting treatment.

Contraception

If you are a woman who can become pregnant, you must use effective contraception to prevent pregnancy while taking Tepkinly and for at least 4 months after the last dose of Tepkinly. If you become pregnant during this time, you must speak to your doctor immediately.

Talk to your doctor or nurse about suitable contraceptive methods.

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 your baby.

Fertility

The effect of Tepkinly on fertility in men and women 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 of sodium (23 mg) per vial; therefore, it is essentially "sodium-free."

Tepkinly contains sorbitol

This medicine contains 28.8 mg of sorbitol in each vial, equivalent to 27.33 mg/ml.

Tepkinly contains polysorbate

This medicine contains 0.42 mg of polysorbate 80 in each vial, equivalent to 0.4 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Tepkinly

A doctor experienced in cancer treatment will manage your therapy. Follow the treatment schedule explained to you by your doctor.

Tepkinly will be administered by a doctor or nurse as a subcutaneous injection.

Tepkinly will be given to you in 28-day cycles, according to a dosing schedule provided by your doctor.

Tepkinly will be administered according to the following schedule:

Table with two columns, Cycle and Schedule of Doses, indicating weekly doses for cycles 1-3, biweekly for cycles 4-9, and monthly from cycle 10 onward

You may be given other medicines before Tepkinly is administered. 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) when Tepkinly is administered:

It is important that you stay well hydrated. Therefore, your doctor may ask you to drink plenty of water the day before and the day after receiving Tepkinly. On the day of Tepkinly administration, your doctor may give you fluids through a needle inserted into a vein (intravenous infusion).
If you are taking any medication for high blood pressure, your doctor may ask you to stop taking it for a short period while you are being treated 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.

If you have follicular lymphoma (FL):

The first full dose (48 mg) of Tepkinly will be administered on Day 22 of Cycle 1.

Your doctor will monitor how well your treatment is working. You will continue to receive Tepkinly as long as your doctor considers that you are benefiting from the treatment.

Your doctor may delay or completely stop treatment with Tepkinly if you experience certain adverse effects.

If you forget to use Tepkinly

If you miss or skip a medical appointment, reschedule it immediately. To ensure the treatment is fully effective, it is very important not to miss any doses.

If you interrupt treatment with Tepkinly

Do not interrupt treatment with Tepkinly unless you have discussed it with your doctor. This is because interrupting treatment may cause your condition to worsen.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Tell your doctor immediately if you notice any of the symptoms listed below related to the following serious adverse effects. 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 lightheadedness
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 occur days or even weeks after receiving the injection, may be subtle at first. Some of these symptoms may 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

Tumor lysis syndrome (TLS) (Common: may affect up to 1 in 10 people)

Symptoms may include:

fever
chills
vomiting
confusion/disorientation
difficulty breathing
seizures
irregular heartbeat
dark or cloudy urine
unusual tiredness
muscle or joint pain

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

a condition in which the immune system produces an excessive number of cells that normally fight infections, called histiocytes and lymphocytes

Symptoms may include:

fever
skin rash
swollen lymph nodes
breathing problems
easy bruising

Other adverse effects

Tell your doctor or nurse immediately if you notice any of the following adverse effects or if they worsen:

Very common: may affect more than 1 in 10 people

Viral infection
pneumonia (lung infection)
upper respiratory tract infections (infections of the airways)
decreased appetite
pain in bones, joints, ligaments, and muscles
abdominal pain
headache
nausea
diarrhea
skin rash
fatigue
injection site reactions
fever
swelling

Shown in blood tests:

low levels of a type of white blood cell that fights infections (neutropenia)
low levels of red blood cells, which may cause fatigue, paleness, and shortness of breath (anemia)
low levels of platelets, which may lead to bleeding and bruising (thrombocytopenia)
decrease in a type of white blood cell called lymphocytes, which may affect the body's ability to fight infections (lymphopenia)
low levels of immunoglobulins, which may lead to infections

Common: may affect up to 1 in 10 people

fever due to infection when white blood cell levels are low (febrile neutropenia)
painful swelling of lymph nodes, chest pain, cough or difficulty breathing, pain in the tumor area (tumor flare)
fungal infections (caused by a type of fungus called Candida)
skin infections
body's response to an infection (sepsis)
rapid breakdown of tumor cells in the blood leading to chemical changes in the blood and damage to organs, including the kidneys, heart, and liver (tumor lysis syndrome)
irregular heartbeat
excess fluid around the lungs that may make breathing difficult (pleural effusion)
vomiting
itching (pruritus)

Shown in blood tests:

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

Reporting of adverse effects

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

5. Storage of Tepkinly

Your doctor, nurse, or pharmacist will store Tepkinly at the hospital or medical center. To properly store Tepkinly:

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 packaging following EXP. The expiry date refers to the last day of the month indicated.
Store and transport refrigerated (between 2 °C and 8 °C).
Do not freeze.
Keep the vial in its outer packaging to protect it from light.
Tepkinly 4 mg/0.8 ml is a solution that may be diluted before use.
- Dilute prior to subcutaneous use for doses of 0.16 mg and 0.8 mg.
- Dilution is not required for the 3 mg dose.
If not used immediately, the prepared solution can be stored at between 2 °C and 8 °C for up to 24 hours 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 preparation until administration.
Allow the solution to reach room temperature before use.

Your doctor, nurse, or pharmacist will dispose of any unused medicine according to local regulations. This helps protect the environment.

6. Contents of the pack and other information

Composition of Tepkinly

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, water for injections (see section 2 “Tepkinly contains sodium”, “Tepkinly contains sorbitol” and “Tepkinly contains polysorbate 80”).

Appearance of Tepkinly and contents of the pack

Tepkinly is an injectable solution. It is a solution ranging from colourless to slightly yellow supplied in a glass vial.

Each pack contains 1 vial.

Marketing Authorization 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 more information about this medicinal product, you may contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium

AbbVie SA

Tel/Tel: +32 10 477811

Lithuania

AbbVie UAB

Tel: +370 5 205 3023

Text in Cyrillic characters on a white background showing the word Bulgaria, the name Abvi EOOD, and a Bulgarian telephone number

Luxembourg/Luxembourg

AbbVie SA

Belgium/Belgium

Tel/Tel: +32 10 477811

Czech Republic

AbbVie s.r.o.

Tel: +420 233 098 111

Hungary

AbbVie Kft.

Tel: +36 1 455 8600

Denmark

AbbVie A/S

Tlf: +45 72 30-20-28

Malta

V.J.Salomone Pharma Limited

Tel: +356 21220174

Germany

AbbVie Deutschland GmbH & Co. KG

Tel: 00800 222843 33 (toll-free)

Tel: +49 (0) 611 / 1720-0

Netherlands

AbbVie B.V.

Tel: +31 (0)88 322 2843

Estonia

AbbVie OÜ

Tel: +372 623 1011

Norway

AbbVie AS

Tlf: +47 67 81 80 00

Greece

AbbVie PHARMACEUTICAL COMPANY S.A.

Tel: +30 214 4165 555

Austria

AbbVie GmbH

Tel: +43 1 20589-0

Spain

AbbVie Spain, S.L.U.

Tel: +34 91 384 09 10

Poland

AbbVie Sp. z o.o.

Tel: +48 22 372 78 00

France

AbbVie

Tél: +33 (0) 1 45 60 13 00

Portugal

AbbVie, Lda.

Tel: +351 (0)21 1908400

Croatia

AbbVie d.o.o.

Tel: +385 (0)1 5625 501

Romania

AbbVie S.R.L.

Tel: +40 21 529 30 35

Ireland

AbbVie Limited

Tel: +353 (0)1 4287900

Slovenia

AbbVie Biofarmacevtska družba d.o.o.

Tel: +386 (1)32 08 060

Iceland

Vistor.

Tel: +354 535 7000

Slovakia

AbbVie s.r.o.

Tel: +421 2 5050 0777

Italy

AbbVie S.r.l.

Tel: +39 06 928921

Finland

AbbVie Oy

Puh/Tel: +358 (0)10 2411 200

Cyprus

Lifepharma (Z.A.M.) Ltd

Tel: +357 22 34 74 40

Sweden

AbbVie AB

Tel: +46 (0)8 684 44 600

Latvia

AbbVie SIA

Tel: +371 67605000

Date of the most recent review of this leaflet

This medicinal product has been authorised under a “conditional approval”. This type of approval means that further information on this medicinal product is expected.

The European Medicines Agency will review new information on this medicinal product at least once a year, and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The most up-to-date and approved package leaflet and patient information card for this medicinal product are available by scanning the QR code included in this leaflet and on the outer carton with a smartphone. 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

This leaflet is available on the European Medicines Agency’s website in all languages of the European Union/European Economic Area.

This information is intended for healthcare professionals only:

This section should be read carefully in full before preparing epcoritamab. Some doses (the priming dose (0.16 mg) and the intermediate dose (0.8 mg)) of epcoritamab must be diluted before administration. All instructions provided below must be followed, as improper 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 vial of epcoritamab is for single use only.

Each vial contains an overfill to allow extraction of the indicated amount.

Epcoritamab must be diluted and administered by a healthcare professional using an aseptic technique.

Filtration of the diluted solution is not required.

Epcoritamab should be inspected visually for particles and discoloration prior to administration. The injectable solution should be a colourless to slightly yellow solution. Do not use if the solution shows discoloration, is cloudy, or contains foreign particles.

Preparation of epcoritamab dilution using the sterile empty vial method

Instructions for preparing the 0.16 mg priming dose – 2 dilutions required – sterile empty vial method

Use a new syringe and needle of appropriate size for each transfer step.

Prepare the Tepkinly vial
1. Remove one 4 mg/0.8 ml vial of Tepkinly with the light blue closure cap from the refrigerator.
2. Allow the vial to reach room temperature for no more than 1 hour.
3. Gently agitate the Tepkinly vial.