Rybrevant 350 mg concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Rybrevant 350 mg concentrate for solution for infusion

amivantamab

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

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Rybrevant is and what it is used for
2. What you need to know before receiving Rybrevant
3. How Rybrevant is given
4. Possible side effects
5. How to store Rybrevant
6. Contents of the pack and other information

1. What Rybrevant is and what it is used for

What Rbrevant is

Rybrevant is a cancer medicine. It contains the active substance amivantamab, which is an antibody (a type of protein) designed to recognize and bind to specific targets in the body.

What Rbrevant is used for

Rybrevant is used in adults with a type of lung cancer called non-small cell lung cancer. It is used when the cancer has spread to other parts of the body and has certain changes (exon 20 insertion mutations) in a gene called EGFR.

How Rbrevant works

The active substance in Rbrevant, amivantamab, targets two proteins present on cancer cells:

• the epidermal growth factor receptor (EGFR), and
• the mesenchymal-epithelial transition factor (MET).

This medicine works by binding to these proteins. This may help slow down or stop the growth of lung cancer. It may also help reduce the size of the tumor.

2. What you need to know before starting Rybrevant

Do not use Rybrevant if

• you are allergic to amivantamab or to any of the other ingredients of this medicine (listed in section 6).

Do not use this medicine if any of the above applies to you. If you are unsure, speak with your doctor or nurse before using this medicine.

Warnings and precautions

Tell your doctor or nurse before starting Rybrevant if:

• you have ever had lung inflammation (a condition called “interstitial lung disease” or “pneumonitis”).

Tell your doctor or nurse immediately if you experience any of the following side effects while receiving this medicine (for more information, see section 4):

• Any side effect while the medicine is being administered intravenously.
• Sudden difficulty breathing, cough, or fever, which may indicate lung inflammation.
• Skin problems. To reduce the risk of skin problems, avoid sunlight, wear protective clothing, apply sunscreen, and regularly use moisturizing creams on your skin and nails while taking this medicine. You must continue doing this for 2 months after stopping treatment.
• Eye problems. If you experience vision changes or eye pain, contact your doctor or nurse immediately. If you wear contact lenses and develop any new eye symptoms, stop using them and inform your doctor immediately.

Children and adolescents

Do not give this medicine to children or adolescents under 18 years of age. This is because it is not known whether the medicine is safe and effective in this age group.

Other medicines and Rybrevant

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

Contraception

• If you can become pregnant, you must use an effective method of contraception during treatment with Rybrevant and for 3 months after stopping treatment.

Pregnancy

• If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor or nurse before receiving this medicine.
• This medicine may be harmful to the unborn baby. If you become pregnant while being treated with this medicine, inform your doctor or nurse immediately. You and your doctor will decide whether the benefit of taking the medicine outweighs the risk to the fetus.

Breast-feeding

It is not known whether Rybrevant passes into breast milk. Consult your doctor before receiving this medicine. You and your doctor will decide whether the benefit of breast-feeding outweighs the risk to your baby.

Driving and using machines

If you feel tired, dizzy, or have irritated eyes or impaired vision after using Rybrevant, do not drive or operate machinery.

Rybrevant contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially “sodium-free”. However, Rybrevant may be mixed with a solution containing sodium before administration. Consult your doctor if you are on a low-salt diet.

3. How Rybrevant is administered

How much Rybrevant to use

Your doctor will determine the correct dose of Rybrevant for you. The dose of this medicine will depend on your body weight at the start of treatment.

The recommended dose of Rybrevant is:

• 1,050 mg if you weigh less than 80 kg.
• 1,400 mg if you weigh 80 kg or more.

How to use the medicine

This medicine will be administered by a doctor or nurse. It is given as an intravenous infusion (a "drip" into a vein) over several hours.

Rybrevant is administered as follows:

• once a week for the first 4 weeks
• and then once every 2 weeks starting from week 5, for as long as you continue to benefit from treatment.

During the first week, your doctor will administer the dose of Rybrevant split over two days.

Medicines given during treatment with Rybrevant

Before each Rybrevant infusion, you will be given medicines to help reduce the chance of infusion-related reactions. These may include:

• medicines for allergic reactions (antihistamines)
• medicines for inflammation (corticosteroids)
• medicines for fever (such as paracetamol).

You may also be given additional medicines depending on any symptoms you experience.

If you receive more Rybrevant than you should

This medicine will be administered by your doctor or nurse. In the unlikely event that you receive too much (an overdose), your doctor will monitor you for any side effects.

If you miss your appointment for Rybrevant administration

It is very important to attend all your appointments. If you miss an appointment, schedule another one as soon as possible.

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

4. Possible adverse effects

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

Serious side effects

Tell your doctor or nurse immediately if you notice any of the following serious side effects:

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

• Signs of an infusion-related reaction – such as chills, feeling short of breath, nausea, flushing, chest discomfort, and vomiting during administration of the medicine. This may occur especially with the first dose. Your doctor may give you other medicines, or it may be necessary to slow down or stop the infusion.
• Skin problems – such as rash (including acne), infected skin around the nails, dry skin, itching, pain, and redness. Inform your doctor if your skin or nail problems worsen.

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

• Eye problems – such as dry eyes, swollen eyelids, itchy eyes, vision problems, eyelash growth.
• Signs of lung inflammation – such as sudden difficulty breathing, cough, or fever. This could lead to permanent damage («interstitial lung disease»). Your doctor may decide to stop treatment with Rybrevant if you experience this side effect.

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

• inflamed cornea (front part of the eye)
• inflammation inside the eye that may affect vision
• potentially life-threatening skin rash with blistering and peeling of the skin over large areas of the body (toxic epidermal necrolysis)

Other side effects

Tell your doctor immediately if you notice any of the following side effects:

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

• low blood levels of the protein "albumin"
• swelling due to fluid accumulation in the body
• feeling of severe tiredness
• mouth sores
• constipation or diarrhoea
• loss of appetite
• increased blood levels of the liver enzyme "alanine aminotransferase", a possible sign of liver problems
• increased blood levels of the enzyme "aspartate aminotransferase", a possible sign of liver problems
• feeling dizzy
• increased blood levels of the enzyme "alkaline phosphatase"
• muscle pain
• low blood calcium levels

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

• stomach pain

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor or nurse, even if they are adverse effects not listed in this leaflet. You may 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 Rybrevant

Rybrevant will be stored in the hospital or medical center.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and label of the vial following "EXP". The expiry date refers to the last day of the month indicated.

Chemical and physical stability during use has been demonstrated for 10 hours at a temperature of 15 °C to 25 °C under ambient light conditions. From a microbiological standpoint, unless the dilution method prevents the risk of microbial contamination, the product should be used immediately. If immediate use is not possible, the times and conditions of storage during use are the responsibility of the user.

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

Keep in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Unused medicines will be disposed of by your healthcare professional. This will help protect the environment.

6. Contents of the pack and other information

Composition of Rybrevant

• The active substance is amivantamab. One ml of concentrate for infusion solution contains 50 mg of amivantamab. A 7 ml vial of concentrate contains 350 mg of amivantamab.
• The other components are ethylenediaminetetraacetic acid (EDTA), L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 80, sucrose, and water for injections (see section 2).

Nature of the product and contents of the container

Rybrevant is a concentrate for infusion solution and is a liquid, ranging from colourless to pale yellow. This medicinal product is supplied in a cardboard pack containing one 7 ml glass vial of concentrate.

Marketing Authorization Holder

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer responsible

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of the most recent review of this summary:

This medicinal product has been authorised under a "conditional approval".

This type of approval means that further information is expected to become available for this medicinal product. The European Medicines Agency will review the new information at least once a year, and this summary 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, and on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

This medicinal product must not be mixed with other medicinal products except those mentioned below.

Prepare the intravenous infusion solution using aseptic technique as follows:

Preparation

• Determine the required dose (1,050 mg or 1,400 mg) and the number of Rybrevant vials needed based on the patient's weight at the reference time. Each Rybrevant vial contains 350 mg of amivantamab.
• Check that the Rybrevant solution is colourless to pale yellow. Do not use if discolouration or visible particles are present.
• Withdraw and discard a volume of 5 % glucose solution or 9 mg/ml (0.9 %) sodium chloride injection solution from the 250 ml infusion bag equal to the volume of Rybrevant solution to be added (discard 7 ml of diluent from the infusion bag for each vial). Infusion bags must be made of polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), or a polyolefin blend (PP+PE).
• Withdraw 7 ml of Rybrevant from each required vial and add it to the infusion bag. Each vial contains an overfill of 0.5 ml to ensure sufficient volume can be withdrawn. The final volume in the infusion bag must be 250 ml. Discard any unused portion remaining in the vial.
• Gently invert the bag to mix the solution. Do not shake.
• Visually inspect for particles and discolouration prior to administration. Do not use if discolouration or visible particles are observed.

Administration

• Administer the diluted solution by intravenous infusion using an infusion set with a flow regulator and an in-line, sterile, pyrogen-free, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometres). Infusion sets must be made of polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE.
• Do not co-infuse Rybrevant simultaneously with other drugs through the same intravenous line.
• The diluted solution must be administered within 10 hours (including infusion time) at room temperature (15 °C to 25 °C) under normal light conditions.
• Due to the frequency of infusion-related reactions (IRR) with the first dose, amivantamab must be administered via peripheral intravenous infusion in Week 1 and Week 2; central venous infusion may be used in subsequent weeks when the risk of IRR is lower.

Disposal

This medicinal product is for single use only. Any unused medicine not administered within 10 hours must be disposed of in accordance with local regulations.