amivantamab: package leaflet

What Rybrevant is
Rybrevant is a cancer medicine. It contains the active substance ‘amivantamab’, which is an antibody (type of protein) designed to recognise and attach 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 your body and has gone through certain changes in a gene called ‘EGFR’.
Rybrevant can be prescribed for you:
 as the first medicine you receive for your cancer in combination with lazertinib.
 in combination with chemotherapy after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI).
 as the first medicine you receive for your cancer in combination with chemotherapy, or  when chemotherapy is no longer working against your cancer.
How Rybrevant works
The active substance in Rybrevant, amivantamab, targets two proteins found on cancer cells:
 epidermal growth factor receptor (EGFR), and
 mesenchymal-epithelial transition factor (MET).
This medicine works by attaching to these proteins. This may help to slow or stop your lung cancer from growing. It may also help to reduce the size of the tumour.
Rybrevant may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflets for these other medicines. If you have any questions about these medicines, ask your doctor.

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 the above applies to you. If you are not sure, talk to your doctor or nurse before you are given this medicine.
Warnings and precautions
Tell your doctor or nurse before you are given Rybrevant if:
 you have suffered from inflammation of your lungs (a condition called ‘interstitial lung disease’ or ‘pneumonitis’).
Tell your doctor or nurse straight away while taking this medicine if you get any of the following side effects (see section 4 for more information):

Any side effect while the medicine is being given into your vein.

Sudden difficulty in breathing, cough, or fever that may suggest inflammation of the lungs. The condition may be life-threatening, therefore healthcare professionals will monitor you for potential symptoms.

When used with another drug called lazertinib; life-threatening side effects (due to blood clots in the veins) may occur. Your doctor will give you additional medication to help prevent blood clots during the course of your treatment and will monitor you for potential symptoms.

Skin problems. To reduce the risk and severity of skin problems, wear protective clothing, apply broad-spectrum UVA/UVB sunscreen, and use moisturisers (ceramide-based or other formulations that provide long-lasting skin hydration and without drying components are preferred) regularly on your face and whole body (except scalp), while taking this medicine.
You will need to keep out of the sun and continue doing this for 2 months after you stop treatment. Your doctor may recommend that you start an antibiotic(s) and an antiseptic to wash your hands and feet to reduce the risk and severity of skin problems, and may treat you with a medicine(s), or send you to see a skin specialist (dermatologist) if you get skin reactions during treatment.

Eye problems. If you have vision problems or eye pain contact your doctor or nurse straight away. If you use contact lenses and have any new eye symptoms, stop using contact lenses and tell your doctor straight away.
Children and adolescents
Do not give this medicine to children or young people below 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 take any other medicines.
Contraception

If you could become pregnant, you must use effective contraception during Rybrevant treatment and for 3 months after stopping treatment.
Pregnancy

Tell your doctor or nurse before you are given this medicine if you are pregnant, think you might be pregnant, or are planning to have a baby.

It is possible that this medicine may harm an unborn baby. If you become pregnant while being treated with this medicine, tell your doctor or nurse straight away. You and your doctor will decide if the benefit of having the medicine is greater than the risk to your unborn baby.

Breast-feeding
It is not known if Rybrevant passes into breast milk. Ask your doctor for advice before being given 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, feel dizzy, or if your eyes are irritated or vision is affected after taking Rybrevant, do not drive or use machinery.
Rybrevant contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. However, before Rybrevant is given to you, it may be mixed with a solution that contains sodium. Talk to your doctor if you are on a low salt diet.
Rybrevant contains polysorbate
This medicine contains 0.6 mg of polysorbate 80 in each mL, which is equivalent to 4.2 mg per 7 mL vial. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

How much is given
Your doctor will work out the correct dose of Rybrevant for you. The dose of this medicine will depend on your body weight at the start of your therapy. You will be treated with Rybrevant once every 2 or 3 weeks according to the treatment your doctor decides for you.
The recommended dose of Rybrevant every 2 weeks is:

1 050 mg if you weigh less than 80 kg.

1 400 mg if you weigh more than or equal to 80 kg.
The recommended dose of Rybrevant every 3 weeks is:

1 400 mg for the first 4 doses and 1 750 mg for subsequent doses if you weigh less than 80 kg.

1 750 mg for the first 4 doses and 2 100 mg for subsequent doses if you weigh more than or equal to 80 kg.
How the medicine is given
This medicine will be given to you by a doctor or nurse. It is given as a drip into a vein (‘intravenous infusion’) over several hours.
Rybrevant is given as follows:
 once a week for the first 4 weeks
 then once every 2 weeks starting at week 5 or once every 3 weeks starting at week 7, for as long as you keep getting benefit from the treatment.
In the first week, your doctor will give you the Rybrevant dose split over two days.
Medicines given during treatment with Rybrevant
Before each infusion of Rybrevant, you will be given medicines which help lower the chance 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 based on any symptoms you may experience.

If you are given more Rybrevant than you should
This medicine will be given by your doctor or nurse. In the unlikely event that you are given too much (an overdose), your doctor will check you for side effects.
If you forget your appointment to have Rybrevant
It is very important to go to all your appointments. If you miss an appointment, make another one as soon as possible.
If you have any further questions on the use of this medicine, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse straight away if you notice the following serious side effects:
Very common (may affect more than 1 in 10 people):

Signs of a reaction to the infusion - such as chills, feeling short of breath, feeling sick (nausea), flushing, chest discomfort, and vomiting while the medicine is being given. This can happen especially with the first dose. Your doctor may give you other medicines, or the infusion may need to be slowed down or stopped.

When given together with lazertinib or chemotherapy (carboplatin and pemetrexed), a blood clot in the veins, especially in the lungs or legs can occur. Signs may include sharp chest pain, shortness of breath, rapid breathing, leg pain, and swelling of your arms or legs.
Common (may affect up to 1 in 10 people):

Signs of an inflammation in the lungs - such as sudden difficulty in breathing, cough, or fever.
This could lead to permanent damage (‘interstitial lung disease’). Your doctor may wish to stop Rybrevant if you get this side effect.

Signs of an inflamed cornea, which is the front part of the eye (keratitis) – such as eye pain, sensitivity to light, redness, changes in vision or eye discharge. If you experience these symptoms you should discontinue use of contact lenses until you have spoken to your doctor.
Uncommon (may affect up to 1 in 100 people):
 life-threatening rash with blisters and peeling skin over much of the body (toxic epidermal necrolysis).
 inflammation inside the eye that may affect vision (uveitis).
Other side effects
Very common (may affect more than 1 in 10 people):
 skin rash
 nail problems
 low number of a type of white blood cell (neutropenia)b
 low level of the protein ‘albumin’ in the blood
 liver problemsa
 swelling caused by fluid build up in the body (oedema)
 nausea
 sores in the mouth
 feeling very tired
 low number of ‘platelets’ (cells that help blood to clot)b
 constipation
 unusual feeling in the skin (such as tingling or a crawling feeling)a
 decreased appetite
 diarrhoea
 increased level of the liver enzyme ‘alanine aminotransferase’ in the blood

 dry skin
 itching
 increased level of the liver enzyme ‘aspartate aminotransferase’ in the blood
 vomiting
 low level of calcium in the blood
 other eye problems
 low level of potassium in the blood
 muscle spasmsa
 fever
 low level of magnesium in the blood
 feeling dizzy
 muscle aches
 increased level of the liver enzyme ‘alkaline phosphatase’ in the blood
 stomach pain.
Common (may affect up to 1 in 10 people):
 haemorrhoids
 redness, swelling, peeling or tenderness, mainly on the hands or feet (palmar-plantar erythrodysaesthesia syndrome)  ulcer (sore) on the skin  problems with vision  growth of eyelashes  hives.a a Only seen in combination with lazertinib b Only seen in combination with carboplatin and pemetrexed Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 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.

Rybrevant will be stored at the hospital or clinic.
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 the vial label after “EXP”. The expiry date refers to the last day of that month.
Chemical and physical in-use stability has been demonstrated for 10 hours at 15°C to 25°C in room 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 to 8°C). Do not freeze.
Store in the original package in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will throw away any medicines that are no longer being used. These measures will help protect the environment.

What Rybrevant contains

The active substance is amivantamab. One mL of concentrate for solution for infusion contains 50 mg of amivantamab. One vial of 7 mL concentrate contains 350 mg of amivantamab.

The other ingredients are ethylenediaminetetraacetic acid (EDTA) disodium salt dihydrate, L- histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 80 (E433), sucrose, and water for injections (see section 2).
What Rybrevant looks like and contents of the pack
Rybrevant is a concentrate for solution for infusion and is a colourless to pale yellow liquid. This medicine is available in a carton pack containing 1 glass vial of 7 mL of concentrate.
Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium
Manufacturer
Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: 0800 93 377 info_belux@its.jnj.com
Lietuva
UAB “JOHNSON & JOHNSON”
Tel: +370 5 278 68 88 lt@its.jnj.com
България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00 jjsafety@its.jnj.com
Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: 800 29 504 info_belux@its.jnj.com
Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227
Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858 janssenhu@its.jnj.com
Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282 jacdk@its.jnj.com
Malta
AM MANGION LTD
Tel: +356 2397 6000
Deutschland
Janssen-Cilag GmbH
Tel: 0800 086 9247 / +49 2137 955 6955 jancil@its.jnj.com
Nederland
Janssen-Cilag B.V.
Tel: 0800 242 42 42 info_nl@its.jnj.com

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410 ee@its.jnj.com
Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00 jacno@its.jnj.com
Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη
Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000
Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300
España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00 contacto@its.jnj.com
Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00
France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 medisource@its.jnj.com
Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600
Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700 jjsafety@JNJCR.JNJ.com
România
Johnson & Johnson România SRL
Tel: +40 21 207 1800
Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122 medinfo@its.jnj.com
Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
JNJ-SI-safety@its.jnj.com
Ísland
Janssen-Cilag AB c/o Vistor ehf.
Sími: +354 535 7000 janssen@vistor.is
Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400
Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1 janssenita@its.jnj.com
Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300 jacfi@its.jnj.com
Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700
Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00 jacse@its.jnj.com
Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561 lv@its.jnj.com
This leaflet was last revised in.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:
This medicinal product must not be mixed with other medicinal products except those mentioned below.
Prepare the solution for intravenous infusion using aseptic technique as follows:
Preparation

Determine the dose required and the number of Rybrevant vials needed based on patient’s baseline weight. Each vial of Rybrevant contains 350 mg of amivantamab.

For every 2-week dosing, patients < 80 kg receive 1 050 mg and for patients ≥80 kg, 1 400 mg once weekly for a total of 4 doses, then every 2 weeks starting at Week 5.

For every 3-week dosing, patients < 80 kg receive 1 400 mg once weekly for a total of 4 doses, then 1 750 mg every 3 weeks starting at Week 7, and for patients ≥80 kg, 1 750 mg once weekly for a total of 4 doses, then 2 100 mg every 3 weeks starting at Week 7.

Check that the Rybrevant solution is colourless to pale yellow. Do not use if discolouration or visible particles are present.

Withdraw and then discard a volume of either 5% glucose solution or sodium chloride 9 mg/mL (0.9%) solution for injection from the 250 mL infusion bag that is equal to the required volume of Rybrevant solution to be added (discard 7 mL diluent from the infusion bag for each vial).
Infusion bags must be made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP+PE).

Withdraw 7 mL of Rybrevant from each vial needed then add it to the infusion bag. Each vial contains a 0.5 mL overfill to ensure sufficient extractable volume. The final volume in the infusion bag should be 250 mL. Discard any unused portion left in the vial.

Gently invert the bag to mix the solution. Do not shake.

Visually inspect for particulate matter 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 fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometer). Administration sets must be made of either polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE.

The administration set with filter must be primed with either 5% glucose solution or 0.9% sodium chloride solution prior to the initiation of each Rybrevant infusion.

Do not infuse Rybrevant concomitantly in the same intravenous line with other agents.

The diluted solution should be administered within 10 hours (including infusion time) at room temperature (15°C to 25°C) and in room light.

Due to the frequency of IRRs at the first dose, amivantamab should be infused via a peripheral vein at Week 1 and Week 2; infusion via a central line may be administered for subsequent weeks when the risk of IRR is lower.
Disposal
This medicinal product is for single use only and any unused medicinal product that is not administered within 10 hours should be disposed of in accordance with local requirements.

What Rybrevant is
Rybrevant is a cancer medicine. It contains the active substance ‘amivantamab’, which is an antibody (type of protein) designed to recognise and attach 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 your body and has gone through certain changes in a gene called ‘EGFR’.
Rybrevant can be prescribed for you:
 as the first medicine you receive for your cancer in combination with lazertinib, or  in combination with chemotherapy (carboplatin and pemetrexed) after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI), or  as the first medicine you receive for your cancer in combination with chemotherapy (carboplatin and pemetrexed), or  when chemotherapy is no longer working against your cancer.
How Rybrevant works
The active substance in Rybrevant, amivantamab, targets two proteins found on cancer cells:
 epidermal growth factor receptor (EGFR), and
 mesenchymal-epithelial transition factor (MET).
This medicine works by attaching to these proteins. This may help to slow or stop your lung cancer from growing. It may also help to reduce the size of the tumour.

Rybrevant may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflets for these other medicines. If you have any questions about these medicines, ask your doctor.

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 the above applies to you. If you are not sure, talk to your doctor or nurse before you are given this medicine.
Warnings and precautions
Tell your doctor or nurse before you are given Rybrevant if:
 you have suffered from inflammation of your lungs (a condition called ‘interstitial lung disease’ or ‘pneumonitis’).
Tell your doctor or nurse straight away while taking this medicine if you get any of the following side effects (see section 4 for more information):

Any side effect while the medicine is injected.

Sudden difficulty in breathing, cough, or fever that may suggest inflammation of the lungs. The condition may be life‑threatening; therefore healthcare professionals will monitor you for potential symptoms.

When used with another drug called lazertinib; life‑threatening side effects (due to blood clots in the veins) may occur. Your doctor will give you additional medication to help prevent blood clots during the course of your treatment and will monitor you for potential symptoms.

Skin problems. To reduce the risk and severity of skin problems, wear protective clothing, apply broad-spectrum UVA/UVB sunscreen, and use moisturisers (ceramide-based or other formulations that provide long lasting skin hydration and without drying components are preferred) regularly on your face and whole body (except scalp), while taking this medicine.
You will need to keep out of the sun and continue doing this for 2 months after you stop treatment. Your doctor may recommend that you start an antibiotic(s) and an antiseptic to wash your hands and feet to reduce the risk and severity of skin problems, and may treat you with a medicine(s), or send you to see a skin specialist (dermatologist) if you get skin reactions during treatment.

Eye problems. If you have vision problems or eye pain, contact your doctor or nurse straight away. If you use contact lenses and have any new eye symptoms, stop using contact lenses and tell your doctor straight away.
Children and adolescents
Do not give this medicine to children or young people below 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 take any other medicines.
Contraception

If you could become pregnant, you must use effective contraception during Rybrevant treatment and for 3 months after stopping treatment.
Pregnancy

Tell your doctor or nurse before you are given this medicine if you are pregnant, think you might be pregnant, or are planning to have a baby.


It is possible that this medicine may harm an unborn baby. If you become pregnant while being treated with this medicine, tell your doctor or nurse straight away. You and your doctor will decide if the benefit of having the medicine is greater than the risk to your unborn baby.
Breast-feeding
It is not known if Rybrevant passes into breast milk. Ask your doctor for advice before being given 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, feel dizzy, or if your eyes are irritated or vision is affected after taking Rybrevant, do not drive or use machinery.
Rybrevant contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
Rybrevant contains polysorbate
This medicine contains 0.6 mg of polysorbate 80 in each mL, which is equivalent to 6 mg per 10 mL vial, 8.4 mg per 14 mL vial, 9 mg per 15 mL vial, or 13.2 mg per 22 mL vial. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

How much is given
Your doctor will work out the correct dose of Rybrevant solution for subcutaneous injection for you.
The dose of this medicine will depend on your body weight at the start of your therapy. You will be treated with Rybrevant once every week for the first 4 weeks, then once every 2, 3 or 4 weeks according to the treatment your doctor decides for you.
Recommended dose of Rybrevant solution for subcutaneous injection when given alone or in combination with lazertinib Every 4 weeks:

1 600 mg weekly for the first 4 doses, and then 3 520 mg every 4 weeks if you weigh less than 80 kg.

2 240 mg weekly for the first 4 doses, and then 4 640 mg every 4 weeks if you weigh more than or equal to 80 kg.
Every 2 weeks:

1 600 mg weekly for the first 4 doses, and then every 2 weeks if you weigh less than 80 kg.

2 240 mg weekly for the first 4 doses, and then every 2 weeks if you weigh more than or equal to 80 kg.
Recommended dose of Rybrevant solution for subcutaneous injection when given in combination with chemotherapy (carboplatin and pemetrexed) Every 3 weeks:

1 600 mg for the first dose, then 2 400 mg weekly for the next 3 doses, and then every 3 weeks if you weigh less than 80 kg.

2 240 mg for the first dose, then 3 360 mg weekly for the next 3 doses, and then every 3 weeks if you weigh more than or equal to 80 kg.
How the medicine is given
Rybrevant solution for subcutaneous injection will be given to you by a doctor or nurse as an injection under your skin (subcutaneous injection) over approximately 5 minutes per injection. It is given in the

stomach area (abdomen), not in other sites of the body, and not into areas of the abdomen where the skin is red, bruised, tender, hard or where there are tattoos or scars.
If you experience pain during the injection, the doctor or nurse may interrupt the injection and give you the remaining injection in another area of your abdomen.
Medicines given during treatment with Rybrevant
Before each injection of Rybrevant, you will be given medicines which help lower the chance of administration-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 based on any symptoms you may experience.
If you are given more Rybrevant than you should
This medicine will be given by your doctor or nurse. In the unlikely event that you are given too much (an overdose), your doctor will check you for side effects.
If you forget your appointment to have Rybrevant
It is very important to go to all your appointments. If you miss an appointment, make another one as soon as possible.
If you have any further questions on the use of this medicine, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse straight away if you notice the following serious side effects:
Very common (may affect more than 1 in 10 people):

When given together with lazertinib or chemotherapy (carboplatin and pemetrexed), a blood clot in the veins, especially in the lungs or legs can occur. Signs may include sharp chest pain, shortness of breath, rapid breathing, leg pain, and swelling of your arms or legs.

Signs of a reaction to the injection - such as chills, feeling short of breath, feeling sick (nausea), flushing, chest discomfort, and fever. This can happen especially with the first dose. Your doctor may give you other medicines, or the injection may need to be stopped.
Common (may affect up to 1 in 10 people):

Signs of an inflammation in the lungs - such as sudden difficulty in breathing, cough, or fever.
This could lead to permanent damage (‘interstitial lung disease’). Your doctor may wish to stop Rybrevant if you get this side effect.

Signs of an inflamed cornea, which is the front part of the eye (keratitis) – such as eye pain, sensitivity to light, redness, changes in vision or eye discharge. If you experience these symptoms, you should discontinue use of contact lenses until you have spoken to your doctor.
Uncommon (may affect up to 1 in 100 people):
 life-threatening rash with blisters and peeling skin over much of the body (toxic epidermal necrolysis).

Inflammation inside the eye that may affect vision (uveitis).

Other side effects
Very common (may affect more than 1 in 10 people):
 skin rash
 nail problems
 low number of a type of white blood cell (neutropenia)b
 low level of the protein ‘albumin’ in the blood
 feeling very tired
 nausea
 sores in the mouth
 liver problemsa
 swelling caused by fluid build up in the body (oedema)
 low number of ‘platelets’ (cells that help blood to clot)b
 constipation
 diarrhoea
 decreased appetite
 unusual feeling in the skin (such as tingling or a crawling feeling)a
 increased level of the liver enzyme ‘alanine aminotransferase’ in the blood
 increased level of the liver enzyme ‘aspartate aminotransferase’ in the blood
 dry skin
 itching
 vomiting
 low level of potassium in the blood
 other eye problems
 low level of calcium in the blood
 muscle aches
 feeling dizzy
 muscle spasmsa
 fever
 stomach pain
 increased level of the liver enzyme ‘alkaline phosphatase’ in the blood
 low level of magnesium in the blood.
Common (may affect up to 1 in 10 people):
 haemorrhoids
 irritation or pain where the injection is given
 ulcer (sore) on the skin
 problems with vision
 redness, swelling, peeling or tenderness, mainly on the hands or feet (palmar-plantar erythrodysaesthesia syndrome)  growth of eyelashes  hives.a a Only seen in combination with lazertinib b Only seen in combination with carboplatin and pemetrexed Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 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.

Rybrevant solution for subcutaneous injection will be stored at the hospital or clinic.
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 the vial label after “EXP”. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C to 8°C). Do not freeze.
Store in the original package in order to protect from light.
Chemical and physical in-use stability of the prepared syringe has been demonstrated up to 24 hours at 2°C to 8°C followed by up to 24 hours at 15°C to 30°C. From a microbiological point of view, unless the method of dose preparation 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.
Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will throw away any medicines that are no longer being used. These measures will help protect the environment.

What Rybrevant contains

The active substance is amivantamab. One mL of solution contains 160 mg of amivantamab.
One vial of 10 mL of solution for injection contains 1 600 mg of amivantamab. One vial of 14 mL of solution for injection contains 2 240 mg of amivantamab. One vial of 15 mL of solution for injection contains 2 400 mg of amivantamab. One vial of 22 mL of solution for injection for injection contains 3 520 mg of amivantamab.

The other ingredients are recombinant human hyaluronidase (rHuPH20), EDTA disodium salt dihydrate, glacial acetic acid, L-methionine, polysorbate 80 (E433), sodium acetate trihydrate, sucrose, and water for injections (see “Rybrevant contains sodium” and “Rybrevant contains polysorbate” in section 2).
What Rybrevant looks like and contents of the pack
Rybrevant solution for subcutaneous injection is a colourless to pale yellow liquid. This medicine is available in a carton pack containing 1 glass vial of 10 mL of solution, 1 glass vial of 14 mL of solution, 1 glass vial of 15 mL of solution or 1 glass vial of 22 mL of solution.
Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium
Manufacturer
Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: 0800 93 377 info_belux@its.jnj.com
Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88 lt@its.jnj.com
България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00 jjsafety@its.jnj.com
Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: 800 29 504 info_belux@its.jnj.com
Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227
Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858 janssenhu@its.jnj.com
Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282 jacdk@its.jnj.com
Malta
AM MANGION LTD
Tel: +356 2397 6000
Deutschland
Janssen-Cilag GmbH
Tel: 0800 086 9247 / +49 2137 955 6955 jancil@its.jnj.com
Nederland
Janssen-Cilag B.V.
Tel: 0800 242 42 42 info_nl@its.jnj.com
Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410 ee@its.jnj.com
Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00 jacno@its.jnj.com
Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη
Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000
Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300
España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00 contacto@its.jnj.com
Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00
France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 medisource@its.jnj.com
Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600
Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700 jjsafety@JNJCR.JNJ.com
România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122 medinfo@its.jnj.com
Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
JNJ-SI-safety@its.jnj.com
Ísland
Janssen-Cilag AB c/o Vistor ehf.
Sími: +354 535 7000 janssen@vistor.is
Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400
Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1 janssenita@its.jnj.com
Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300 jacfi@its.jnj.com
Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700
Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00 jacse@its.jnj.com
Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561 lv@its.jnj.com
This leaflet was last revised in.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency website:
https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:
Rybrevant subcutaneous formulation should be administered by a healthcare professional.
To prevent medication errors, it is important to check the vial labels to ensure that the appropriate formulation (intravenous or subcutaneous formulation) and dose is being given to the patient as prescribed. Rybrevant subcutaneous formulation should be given by subcutaneous injection only, using the dose specified. Rybrevant subcutaneous formulation is not intended for intravenous administration.
This medicinal product must not be mixed with other medicinal products except those mentioned below.
Prepare the solution for subcutaneous injection using aseptic technique as follows:
Preparation

Determine the dose required and the appropriate Rybrevant subcutaneous formulation vial(s) needed based on patient’s baseline weight.

For every 4-week dosing, patients < 80 kg receive 1 600 mg weekly from Weeks 1 to 4, then 3 520 mg every 4 weeks starting at Week 5 onwards. Patients ≥ 80 kg receive 2 240 mg weekly from Weeks 1 to 4, then 4 640 mg every 4 weeks starting at Week 5 onwards.

For every 2-week dosing, patients < 80 kg receive 1 600 mg and patients ≥80 kg receive 2 240 mg weekly from Weeks 1 to 4, and then every 2 weeks starting at Week 5 onwards.

For every 3-week dosing, patients < 80 kg receive 1 600 mg on Week 1 Day 1, then 2 400 mg weekly from Weeks 2 to 4, and then every 3 weeks starting at Week 7 onwards. Patients ≥ 80 kg receive 2 240 mg on Week 1 Day 1, then 3 360 mg weekly from Weeks 2 to 4, and then every 3 weeks starting at Week 7 onwards.

Remove the appropriate Rybrevant subcutaneous formulation vial(s) from refrigerated storage (2°C to 8°C).

Check that the solution is colourless to pale yellow. Do not use if opaque particles, discolouration or other foreign particles are present.

Equilibrate Rybrevant subcutaneous formulation to room temperature (15°C to 30°C) for at least 15 minutes. Do not warm Rybrevant subcutaneous formulation in any other way. Do not shake.

Withdraw the required injection volume of Rybrevant subcutaneous formulation from the vial into an appropriately sized syringe using a transfer needle. Smaller syringes require less force during preparation and administration.

Each injection volume should not exceed 15 mL. Divide doses requiring greater than 15 mL into approximately equal volumes in multiple syringes.

Rybrevant subcutaneous formulation is compatible with stainless steel injection needles, polypropolene and polycarbonate syringes, and polyethylene, polyurethan, and polyvinylchloride subcutaneous infusion sets. A sodium chloride 9 mg/mL (0.9%) solution may also be used to flush an infusion set if needed.

Replace the transfer needle with the appropriate ancillaries for transport or administration. Use of a 21G to 23G needle or infusion set is recommended to ensure ease of administration.
Storage of prepared syringe
The prepared syringe should be administered immediately. If immediate administration is not possible, store the prepared syringe refrigerated at 2°C to 8°C for up to 24 hours followed by at room temperature of 15°C to 30°C for up to 24 hours. The prepared syringe should be discarded if stored for more than 24 hours refrigerated or more than 24 hours at room temperature. If stored in the refrigerator, allow the solution to come to room temperature before administration.
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Disposal
This medicinal product is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.