Rybrevant - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Rybrevant 350 mg concentrate for solution for infusion amivantamab

This medicine is subject to additional monitoring. This will allow quick identification of new safetyinformation. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given 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.

What is in this leaflet

• 1. What Rybrevant is and what it is used for

• 2. What you need to know before you are given 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 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 (Exon 20 insertion mutations) in a gene called ‘EGFR’.

How Rybrevant works

he active substance in Rybrevant, amivantamab, targets two proteins found on cancer cells:

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

his 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.

2. What you need to know before you are given 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 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

ell 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.
• Skin problems. To reduce the risk of skin problems, keep out of the sun, wear protective

clothing, apply sunscreen, and use moisturisers regularly on your skin and nails while taking this medicine. You will need to continue doing this for 2 months after you stop 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.

• 3. How Rybrevant is given

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.

The recommended dose of Rybrevant is:

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

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 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.

• 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, problems with vision, growth of

eyelashes.

• 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.

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

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

necrolysis).

Other side effects

Tell your doctor 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 build up in the body
• feeling very tired
• sores in the mouth
• constipation or diarrhoea
• decreased appetite
• increased level of the liver enzyme ‘alanine aminotransferase’ in the blood, a possible sign of

liver problems

• increased level of the enzyme ‘aspartate aminotransferase’ in the blood, a possible sign of liver

problems

• feeling dizzy
• increased level of the enzyme ‘alkaline phosphatase’ in the blood
• muscle aches
• low level of calcium in the blood.

Common (may affect up to 1 in 10 people)

• stomach pain.

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.

5. How to store Rybrevant

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.

6. Contents of the pack and other information

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), L-histidine, L-histidine

hydrochloride monohydrate, L-methionine, polysorbate 80, 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:

Belgie/Belgiqu­e/Belgien Janssen-Cilag NV Tel/Tél: +32 14 64 94 11	Lietuva UAB “JOHNSON & JOHNSON Tel: +370 5 278 68 88
Etarapuu ..^■/KOHCbH & ^>kohcuh Ebarapua” EOOfl Tea.: +359 2 489 94 00	Luxembourg/Lu­xemburg Janssen-Cilag NV Tél/Tel: +32 14 64 94 11
Česká republika Janssen-Cilag s.r.o. Tel: +420 227 012 227	Magyarorszag Janssen-Cilag Kft. Tel.: +36 1 884 2858
Danmark Janssen-Cilag A/S Tlf: +45 4594 8282	Malta AM MANGION LTD Tel: +356 2397 6000
Deutschland Janssen-Cilag GmbH Tel: +49 2137 955 955	Nederland Janssen-Cilag B.V. Tel: +31 76 711 1111

Eesti UAB „JOHNSON & JOHNSON“ Eesti filiaal Tel: +372 617 7410	Norge Janssen-Cilag AS Tlf: +47 24 12 65 00
EÀÀàôa Janssen-Cilag OappaKauTiK^ A.E.B.E. Tql: +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	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	Portugal Janssen-Cilag Farmacêutica, Lda. Tel: +351 214 368 600
Hrvatska Johnson & Johnson S.E. d.o.o. Tel: +385 1 6610 700	România Johnson & Johnson România SRL Tel: +40 21 207 1800
Ireland Janssen Sciences Ireland UC Tel: +353 1 800 709 122	Slovenija Johnson & Johnson d.o.o. Tel: +386 1 401 18 00
Ísland Janssen-Cilag AB c/o Vistor hf. Sími: +354 535 7000	Slovenská republika Johnson & Johnson, s.r.o. Tel: +421 232 408 400
Italia Janssen-Cilag SpA Tel: 800.688.777 / +39 02 2510 1	Suomi/Finland Janssen-Cilag Oy Puh/Tel: +358 207 531 300
Kùnpoç Bapváßaç XaTZnnavaY^ç Ató Tip.: +357 22 207 700	Sverige Janssen-Cilag AB Tfn: +46 8 626 50 00
Latvija UAB „JOHNSON & JOHNSON“ filiäle Latvijä Tel: +371 678 93561	United Kingdom (Northern Ireland) Janssen Sciences Ireland UC Tel: +44 1 494 567 444

This leaflet was last revised in.

This medicine has been given ‘conditional approval’.

This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

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 (either 1,050 mg or 1,400 mg) and the number of Rybrevant vials

needed based on patient’s baseline weight. Each vial of Rybrevant 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 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.

• 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.

ANNEX IV

CONCLUSIONS ON THE GRANTING OF THE CONDITIONAL MARKETING AUTHORISATION PRESENTED BY THE EUROPEAN MEDICINES AGENCY

Conclusions presented by the European Medicines Agency on:

• Conditional marketing authorisation

The CHMP having considered the application is of the opinion that the risk-benefit balance is favourable to recommend the granting of the conditional marketing authorisation as further explained in the European Public Assessment Report.

33

Grade 3 events only

a Hypoalbuminaemia: blood albumin decreased, hypoalbuminaemia

b Dizziness: dizziness, dizziness exertional, vertigo

c Visual impairment: vision blurred, visual acuity reduced, visual impairment

d Growth of eyelashes: growth of eyelashes, trichomegaly

e Other eye disorders: blepharitis, conjunctival hyperaemia, corneal irritation, dry eye, episcleritis, eye disorder, eye pruritus, noninfective conjunctivitis, ocular hyperaemia

f Interstitial lung disease: interstitial lung disease, pneumonitis

g Stomatitis: aphthous ulcer, cheilitis, glossitis, lip ulceration, mouth ulceration, mucosal inflammation, stomatitis

h Abdominal pain: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, epigastric discomfort, gastrointesti­nal pain

i Rash: acne, dermatitis, dermatitis acneiform, erythema, erythema multiforme, folliculitis, impetigo, palmar-plantar erythrodysaesthesia syndrome, perineal rash, perioral dermatitis, pustule, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular, skin exfoliation, skin lesion

j Nail toxicity: ingrowing nail, nail bed infection, nail cuticle fissure, nail disorder, nail ridging, onychoclasis, onycholysis, paronychia

k Dry skin: dry skin, eczema, eczema asteatotic, skin fissures, xeroderma

l Oedema: eye oedema, eyelid oedema, face oedema, generalised oedema, localised oedema, oedema, oedema peripheral, periorbital oedema, periorbital swelling, peripheral swelling, swelling face

m Fatigue: asthenia, fatigue