RYBREVANT 350 mg concentrate for infusion solution

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 quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Rybrevant and what is it used for
2. What you need to know before you receive Rybrevant
3. How Rybrevant is administered
4. Possible side effects
5. Storage of Rybrevant
6. Contents of the pack and further information

1. What is Rybrevant and what is it used for

What is Rybrevant

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 Rybrevant 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 undergone certain changes (insertion mutations in Exon 20) in a gene called EGFR.

How Rybrevant works

The active substance in Rybrevant, amivantamab, targets two proteins present in 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 you receive Rybrevant

Do not use Rybrevant if

• you are allergic to amivantamab or 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 not sure, talk to your doctor or nurse before using this medicine.

Warnings and precautions

Tell your doctor or nurse before you start receiving Rybrevant if:

• you have had inflammation of the lungs (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 into a vein.
• Sudden difficulty breathing, cough or fever that may indicate the presence of lung inflammation.
• Skin problems. To reduce the risk of skin problems, stay out of the sun, wear protective clothing, apply sunscreen, and use moisturizing creams on the skin and nails while using this medicine. You will also need to continue doing so for 2 months after stopping treatment.
• Eye problems. If you have vision problems or eye pain, contact your doctor or nurse immediately. If you wear contact lenses and have any new eye symptoms, stop wearing 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 if 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 take any other medicines.

Contraceptives

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

Pregnancy

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or nurse before receiving this medicine.
• This medicine may harm your unborn baby. If you become pregnant while using this medicine, tell your doctor or nurse immediately. You and your doctor will decide if the benefit of taking the medicine is greater than the risk to your baby.

Breast-feeding

It is not known if Rybrevant passes into breast milk. Consult your doctor before you receive this medicine. You and your doctor will decide if the benefit of breast-feeding is greater than the risk to your baby.

Driving and using machines

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

Rybrevant contains sodium

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

3. How Rybrevant is administered

How much Rybrevant is used

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 your weight is 80 kg or more.

How to use the medicine

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

Rybrevant is administered as follows:

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

In the first week, your doctor will administer the dose of Rybrevant divided over 2 days.

Medicines administered during treatment with Rybrevant

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

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

You may also be given additional medicines depending on the symptoms you have.

If you receive more Rybrevant than you should

This medicine will be administered by a doctor or nurse. In the unlikely event that you receive too much (an overdose), your doctor will examine you to see if you have any side effects.

If you miss your appointment for Rybrevant administration

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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, shortness of breath, nausea, redness, 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 reduce the infusion rate or stop it.
• Skin problems - such as rash (including acne), infected skin around the nails, dry skin, itching, pain, and redness. Tell your doctor if your skin or nail problems get worse.

Common(may affect up to 1 in 10 people)

• Eye problems - such as dry eye, swollen eyelid, 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 want to stop the administration of Rybrevant if you have this side effect.

Uncommon(may affect up to 1 in 100 people)

• inflammation of the cornea (front part of the eye)
• inflammation inside the eye that can affect vision
• potentially life-threatening rash with blisters and peeling of the skin over much 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 level of the protein albumin in the blood
• swelling caused by fluid accumulation in the body
• feeling of extreme tiredness
• mouth sores
• constipation or diarrhea
• loss of appetite
• increase in the level of the liver enzyme alanine aminotransferase in the blood, a possible sign of liver problems
• increase in the level of the enzyme aspartate aminotransferase in the blood, a possible sign of liver problems
• feeling of dizziness
• increase in the level of the enzyme alkaline phosphatase in the blood
• muscle pain
• low calcium levels in the blood

Common(may affect up to 1 in 10 people)

• stomach pain.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side 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 which is stated on the carton and vial label after EXP. The expiry date is the last day of the month shown.

Chemical and physical stability has been demonstrated for 10 hours at a temperature of 15°C to 25°C with ambient light. From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

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

Store in the original package to protect from light.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will dispose of any unused medicines. This will help protect the environment.

6. Container Contents and Additional Information

Rybrevant Composition

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

Appearance and Container Contents of the Product

Rybrevant is a concentrate for solution for infusion and is a colorless to pale yellow liquid. This medicinal product is presented in a cardboard box containing 1 glass vial of 7 ml of concentrate.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

Netherlands

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

Date of Last Revision of this Leaflet:

This medicinal product has been authorized with a "conditional approval".

This type of approval means that more information on this medicinal product is expected. The European Medicines Agency will review the 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 European Medicines Agency website: http://www.ema.europa.eu, and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended only for healthcare professionals:

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

Prepare the solution for intravenous infusion using an 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 time of reference. Each Rybrevant vial contains 350 mg of amivantamab.
• Check that the Rybrevant solution is colorless to pale yellow. Do not use if there is discoloration or visible particles.
• Withdraw and discard a volume of 5% glucose solution or 9 mg/ml (0.9%) sodium chloride injectable solution from the 250 ml infusion bag that is equal to the required volume of Rybrevant solution to be added (discard 7 ml of diluent from the infusion bag for each vial). The infusion bags must be made of polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), or a mixture of polyolefins (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 extractable volume. The final volume in the infusion bag should 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 discoloration before administration. Do not use if discoloration or particles are visible.

Administration

• Administer the diluted solution by intravenous infusion using an infusion set equipped with a flow regulator and a polyethersulfone (PES) filter in line, sterile, apyrogenic, and with low protein binding (pore size 0.22 or 0.2 microns). The infusion sets must be made of polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE.
• Do not infuse Rybrevant simultaneously in the same intravenous line with other medicinal products.
• The diluted solution should be administered within 10 hours (including infusion time) at room temperature (15°C to 25°C) and ambient light.
• Due to the frequency of IRs in the first dose, amivantamab should be infused by peripheral intravenous route in Week 1 and Week 2; central venous infusion may be administered in subsequent weeks when the risk of IRs is lower.

Disposal

This medicinal product is for single use and disposal of unused medicinal product that is not administered within 10 hours will be carried out in accordance with local regulations.