Tepkinly 4 mg/0,8 ml concentrado para solucion inyectable

Prospect: information for the patient

Tepkinly 4 mg/0.8 ml injectable solution

epcoritamab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospectus carefully before starting to use this medicine, because it contains important information for you.

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

What is Tepkinly

Tepkinly is a cancer medication that contains the active ingredient epcoritamab. Tepkinly is used alone (monotherapy) to treat adult patients who have a type of blood cancer called large B-cell lymphoma (LBCLG) or follicular lymphoma (FL) when the disease has relapsed or not responded to previous treatment after at least two previous treatments.

How Tepkinly works

Epcoritamab is designed specifically to help your own immune system attack cancer cells (lymphoma). Epcoritamab acts by binding to immune cells and cancer cells in your body, bringing them together, so that your immune system can destroy the cancer cells.

No use Tepkinly

If you are allergic to epcoritamab or any of the other components of this medication (listed in section 6).

Consult your doctor or nurse before Tepkinly is administered to you if you are unsure.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Tepkinly if

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

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

Inform your doctor immediately if you experience any of the following adverse effects listed below during or after treatment with Tepkinly. You may need additional medical treatment.

• Cytokine release syndrome:A potentially life-threatening disease that causes fever, vomiting, difficulty breathing/lack of breath, chills, rapid heart rate, headache, and dizziness or mild disorientation, associated with medications that stimulate T cells.

− Before each subcutaneous injection, you may be administered medications that help reduce the possible effects of cytokine release syndrome.

• ICANS (immune effector cell-associated neurotoxicity syndrome):Symptoms may include problems with language use (including speech, understanding, writing, and reading), drowsiness, confusion/disorientation, muscle weakness, seizures, swelling of a part of the brain, and memory loss.
• Infections:You may experience signs of infection, such as a fever of 38 °C or higher, chills, cough, or pain when urinating that may vary depending on the location of the body where the infection is located.
• Tumor lysis syndrome:Some people may present with unusual levels of certain salts in the blood, due to the rapid breakdown of cancer cells during treatment. This is called tumor lysis syndrome (TLS).

• Your doctor or nurse will perform blood tests to check if you have this situation. Before each subcutaneous injection, you must be well-hydrated and you may be administered other medications that can help reduce elevated uric acid levels and reduce the possible effects of tumor lysis syndrome.

• Tumor flare:As your cancer is destroyed, it may react and appear to worsen – this is called "tumor flare."

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 medications and Tepkinly

Inform your doctor or pharmacist if you are taking or using, have taken or used recently, or may need to take or use any other medication. This includes medications obtained without a prescription and herbal medications.

Pregnancy

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

Contraception

If you are a woman who may become pregnant, you must use effective contraceptive methods to avoid becoming pregnant 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 immediately with your doctor.

Discuss suitable contraceptive methods with your doctor or nurse.

Breastfeeding

You should not breastfeed during treatment with Tepkinly and for at least 4 months after the last dose. It is not known if Tepkinly passes into breast milk and if it could affect your baby.

Fertility

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

Driving and operating machinery

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

Tepkinly contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free."

Tepkinly contains sorbitol

This medication contains 21.9 mg of sorbitol in each vial, equivalent to 27.33 mg/ml.

Tepkinly contains polysorbate

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

A doctor with experience in cancer treatment will be in charge of your treatment. Follow the treatment schedule that your doctor explains to you.

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

Tepkinly will be administered in 28-day cycles, according to a dosing schedule that your doctor will provide to you.

Tepkinly will be administered according to the following schedule

You may be administered other medications before administering Tepkinly. This is to help prevent reactions such as cytokine release syndrome and fever in Cycle 1 (and potentially in future cycles).

These medications may include

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

If you have lymphomaB cell lymphoma with large cells (LBCL)

The first full dose (48 mg) of Tepkinly will be administered on Day 15 of Cycle 1. Your doctor will monitor how your treatment is working and will ask you to stay in the hospital for 24 hours after the first full dose (48 mg) because it is when reactions such as SLC, ICANS, and fever are most likely to occur.

If you have follicular lymphoma (FL)

The first full dose (48mg) of Tepkinly will be administered on Day22 of Cycle1.

Tepkinly will be administered while your doctor thinks 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 forget or miss a medical appointment, ask for another one immediately. It is very important not to miss any doses for the treatment to be fully effective.

If you interrupt treatment with Tepkinly

Do not interrupt treatment with Tepkinly unless you have talked to your doctor. This is because interrupting treatment may make your condition worse.

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

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

Severe side effects

Inform your doctor immediately if you notice any of the following severe side effects. You may only experience one or some of these symptoms.

Cytokine Release Syndrome (CRS) (Very common: may affect more than 1 in 10 people)

The symptoms may include

• fever
• vomiting
• dizziness or mild drowsiness
• chills
• rapid heartbeat
• difficulty breathing/lack of breath
• headache

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (Common: may affect up to 1 in 10 people)

• The effects on the nervous system, whose symptoms may occur days or even weeks after receiving the injection, may be subtle at first. Some of those symptoms may be signs of a severe immune reaction called "Immune Effector Cell-Associated Neurotoxicity Syndrome" (ICANS). The 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)

The symptoms may include

• fever
• chills
• vomiting
• confusion/disorientation
• difficulty breathing
• seizures
• irregular heart rhythm
• dark or cloudy urine
• unusual fatigue
• muscle or joint pain

Other side effects

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

Very common: may affect more than 1 in 10 people

• Viral infection
• Pneumonia (lung infection)
• Upper respiratory tract infections (respiratory tract infections)
• Decreased appetite
• Pain in bones, joints, ligaments, and muscles
• Abdominal pain
• Headache
• Nausea
• Diarrhea
• Rash
• Fatigue
• Reaction at the injection site
• Fever
• Inflammation

Shown in blood tests

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

Common: may affect up to 1 in 10 people

• Fever due to infection when having low white blood cell levels (neutropenic fever)
• Painful lymph node inflammation, 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 reaction to an infection (sepsis)
• Rapid breakdown of tumor cells in the blood resulting in changes in blood chemistry and damage to organs, including the kidneys, heart, and liver (tumor lysis syndrome)
• Irregular heartbeat
• Fluid accumulation around the lungs that can make it difficult to breathe (pleural effusion)
• Vomiting
• Rash
• Itching (pruritus)

Shown in blood tests:

• Low levels of phosphates, potassium, magnesium, or sodium
• Increased levels of creatinine in the blood, a waste product of muscle tissue
• Increased levels of liver proteins in the blood, which can show liver problems

Reporting side effects

If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects that do not appear in this prospectus. You can also report them directly through thenational reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

The doctor, nurse or pharmacist will conserve Tepkinly in the hospital or medical center. To conserve Tepkinly correctly

• Keep this medication out of the sight and reach of children
• Do not use this medication after the expiration date that appears on the vial label and packaging after EXP. The expiration date is the last day of the month indicated.
• Conserve and transport refrigerated (between 2 °C and 8 °C).
• Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Tepkinly 4 mg/0.8 ml is a concentrated solution that must be diluted before use.
• • Dilute before subcutaneous use for doses of 0.16 mg and 0.8 mg.
  • No dilution is required for the 3 mg dose.
• If not used immediately, the prepared solution can be conserved at between 2 °C and 8 °C for a maximum of 24 hours from the time of preparation.
• Within these 24 hours, the prepared solution can be conserved for a maximum of 12 hours at room temperature (20 °C - 25 °C) from the start of preparation to administration.
• Allow the solution to reach room temperature before using it.

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

Composition of Tepkinly

• The active principle is epcoritamab. Each vial of 0.8 ml contains 4 mg of epcoritamab at a concentration of 5 mg/ml.
• The other excipients are sodium trihydrate acetate, acetic acid, sorbitol (E420), polisorbate 80, and water for injectable preparations (see section 2 “Tepkinly contains sodium” and “Tepkinly contains sorbitol”).

Appearance of Tepkinly and contents of the package

Tepkinly is an injectable solution. It is a colorless to slightly yellow solution supplied in a glass vial.

Each package 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

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

Last update of this leaflet

This medicinal product has been authorized under a conditional approval. This type of approval means that more information is expected to be obtained about this medicinal product.

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

Other sources of information

The detailed information about this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites about rare diseases and orphan medicinal products.

The leaflet and patient information card for recent and approved medicinal products of this medicinal product are available by scanning the QR code included in this leaflet and in the outer packaging with a smartphone. The same information is also available at the following URL:www.tepkinly.eu

QR code to include

To listen to or request a copy of this leaflet in , or , please contact the local representative of the marketing authorization holder.

This information is only intended for healthcare professionals:

Epcoritamab is prepared and administered as a subcutaneous injection.

Each vial of epcoritamab is for single use only.

Each vial contains an overfill that allows the extraction of the indicated amount.

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

No filtration of the diluted solution is required.

Epcoritamab should be visually inspected to detect particles and color changes before administration. The injectable solution should be a colorless to slightly yellow solution. Do not use if the solution shows color changes, is turbid, or contains foreign particles.

Instructions for preparing the 0.16 mg dose preparation - 2 dilutions are required

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

1. Prepare the Tepkinly vial

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

DO NOTagitate in a vortex or agitate vigorously the vial.

1. Perform the first dilution

1. Label a suitable empty vial as “dilution A”.
2. Transfer0.8 ml of Tepkinlyto the vial ofdilution A.
3. Transfer4.2 ml of sterile sodium chloride 9 mg/ml (0.9 %) solutionto the vial ofdilution Ato obtain a final concentration of 0.8 mg/ml.
4. Gently agitate the vial ofdilution Afor 30-45 seconds.

1. Perform the second dilution

1. Label a suitable empty vial as “dilution B”.
2. Transfer2 ml of solutionfrom the vial ofdilution Ato the vial ofdilution B. The vial ofdilution Ais no longer required and should be discarded.
3. Transfer8 ml of sterile sodium chloride 9 mg/ml (0.9 %) solutionto the vial ofdilution Bto obtain a final concentration of 0.16 mg/ml.
4. Gently agitate the vial ofdilution Bfor 30-45 seconds.

1. Extract the dose

Extract1 ml of epcoritamab dilutedfrom the vial ofdilution Bwith a syringe. The vial ofdilution Bis no longer required and should be discarded.

1. Label the syringe

Label the syringe with the name of the product, the dose concentration (0.16 mg), the date, and the time of the day.

1. Discard the vial and the part of Tepkinly that has not been used in accordance with local regulations.

Instructions for preparing the intermediate dose of 0.8 mg - 1 dilution is required

Use a syringe, a vial, and a needle, of the appropriate size, for each step of transfer.

1. Prepare the Tepkinly vial

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

DO NOTagitate in a vortex or agitate vigorously the vial.

1. Perform the dilution

1. Label a suitable empty vial as “dilution A”.
2. Transfer0.8 ml of Tepkinlyto the vial ofdilution A.
3. Transfer4.2 ml of sterile sodium chloride 9 mg/ml (0.9 %) solutionto the vial ofdilution Ato obtain a final concentration of 0.8 mg/ml.
4. Gently agitate the vial ofdilution Afor 30-45 seconds.

1. Extract the dose

Extract1 ml of epcoritamab dilutedfrom the vial ofdilution Awith a syringe. The vial ofdilution Ais no longer required and should be discarded.

1. Label the syringe

Label the syringe with the name of the product, the dose concentration (0.8 mg), the date, and the time of the day.

1. Discard the vial and the part of Tepkinly that has not been used in accordance with local regulations.

Instructions for preparing the second intermediate dose of 3 mg - no dilution is required

The 3 mg dose of epcoritamab is only required for patients with LF.

1)Prepare the Tepkinly vial

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

DO NOTagitate in a vortex or agitate vigorously the vial.

2)Extract the dose

Extract0.6 ml of epcoritamabwith a syringe.

3)Label the syringe

Label the syringe with the name of the product, the dose concentration (3 mg), the date, and the time of the day.

4)Discard the vial and the part of Tepkinly that has not been used in accordance with local regulations.

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the medicinal product administered must be clearly recorded.