VYLOY

Package leaflet: Information for the patient

Vyloy 100 mg powder for concentrate for solution for infusion, 300 mg powder for concentrate for solution for infusion

zolbetuximab
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicinal product. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What Vyloy is and what it is used for
2. What you must know before being administered Vyloy
3. How Vyloy is administered
4. Possible side effects
5. How to store Vyloy
6. Contents of the pack and other information

1. What Vyloy is and what it is used for

Vyloy contains the active substance zolbetuximab, a monoclonal antibody that can recognize and
bind to certain tumour cells. The binding of the medicine to these tumour cells triggers the
immune system to attack and kill them.
This medicine is used to treat adult patients with gastric (stomach) cancer or gastro-oesophageal junction cancer. The gastro-oesophageal junction is the point where the oesophagus connects to the stomach.
This medicine is given to patients whose tumours are positive for the protein Claudin 18.2 (CLDN18.2) (meaning the protein is produced in the cells) and negative for proteins called “human epidermal growth factor receptor 2 (HER2)” (meaning the protein is not produced or is produced only in small amounts). It is administered to patients whose gastric or gastro-oesophageal junction cancer cannot be surgically removed or has spread to other parts of the body.
This medicine is given in combination with other anticancer medicines containing fluoropyrimidine and/or platinum. It is important that you also read the package leaflets of these other medicines. If you have any doubts about these medicines, consult your doctor.

2. What you need to know before you are given Vyloy

Vyloy must not be administered to you if:

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

Warnings and precautions

Talk to your doctor before you are given this medicine, as it may cause:

• Allergic reactions (hypersensitivity), including anaphylaxis. Severe allergic reactions may occur during or after the infusion. Immediately inform your doctor or seek urgent medical help if you experience any of the following symptoms of a severe allergic reaction:

  • red, swollen, itchy areas of skin (urticaria),
  • persistent cough,
  • breathing problems such as wheezing, or
  • tightness in the throat/voice changes.

• Infusion-related reactions. Severe infusion-related reactions may occur during or after the infusion. Immediately inform your doctor or seek urgent medical help if you experience any of the following symptoms of an infusion-related reaction:

  • nausea (feeling unwell),
  • vomiting (feeling sick),
  • stomach pain,
  • increased salivation (hypersalivation),
  • fever,
  • chest discomfort,
  • chills or trembling,
  • back pain,
  • cough, or
  • high blood pressure (hypertension).

• Nausea and vomiting. Inform your doctor if you experience nausea before the start of the infusion. Nausea and vomiting are very common during treatment and may sometimes be severe. Your doctor may give you another medicine before each infusion to help reduce nausea and vomiting.

Immediately inform your doctor if you experience any of these signs or symptoms, or if they worsen. Your doctor may:

• administer other medicines to relieve symptoms or prevent complications,
• reduce the infusion rate, or
• temporarily or permanently discontinue treatment.

Children and adolescents

Vyloy is not intended for use in children and adolescents, as it has not been studied in this age group for the treatment of gastric cancer or gastro-oesophageal junction cancer.

Other medicines and Vyloy

Tell your doctor if you are taking, have recently taken, or might take any other medicines, including medicines without a prescription.

Pregnancy

Vyloy must not be used during pregnancy unless specifically recommended by your doctor. It is not known whether this medicine may harm the unborn baby. If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.

Breastfeeding

Breastfeeding is not recommended during treatment with Vyloy. It is not known whether this medicine passes into breast milk. Inform your doctor if you are breastfeeding or intend to breastfeed.

Driving and using machines

It is unlikely that Vyloy will affect your ability to drive or use machines.

Vyloy contains polysorbate 80

This medicine contains 1.05 mg and 3.15 mg of polysorbate 80 per 100 mg and 300 mg dose of Vyloy, respectively. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

Vyloy infusion contains sodium

This medicine does not contain sodium; however, a saline solution is used to dilute the product before infusion. Speak with your doctor if you are on a low-salt diet.

3. How Vyloy is administered

Vyloy will be administered to you in a hospital or outpatient clinic under the supervision of a physician experienced in anticancer treatments. This medicine will be given by intravenous infusion (drip) into a vein over a period of at least 2 hours.

How much Vyloy will be administered to you
Your doctor will determine the dose of this medicine to be administered. Generally, this medicine will be given every 2 or 3 weeks, depending on the other anticancer medicines chosen by your doctor. Your doctor will decide how many treatment cycles you will need.

If you miss a dose of Vyloy
It is very important that you do not miss a dose of this medicine. If you miss an appointment, contact your doctor as soon as possible to reschedule.

If you stop treatment with Vyloy
Do not stop treatment with this medicine without first discussing it with your doctor.
Stopping treatment may interrupt the medicine's effect.

If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some possible side effects could be serious:

• Hypersensitivity (allergic) reactions (including hypersensitivity and anaphylactic reaction) – common (may affect up to 1 in 10 people). Inform your doctor immediately or seek urgent medical assistance if you experience any of the following symptoms of a severe allergic reaction: red, swollen, itchy areas of skin (urticaria), persistent cough, breathing problems such as wheezing or tightness in the throat/voice changes.
• Infusion-related reaction – common (may affect up to 1 in 10 people). Inform your doctor immediately or seek urgent medical assistance if you experience any of the following symptoms of an infusion-related reaction: nausea, vomiting, stomach ache, increased salivation (hypersalivation), fever, chest discomfort, chills or shivering, back pain, cough or high blood pressure (hypertension).
• Nausea and vomiting – very common (may affect more than 1 in 10 people). Inform your doctor if these symptoms do not go away or worsen.

Other possible side effects:
Inform your doctor if these side effects worsen.
Very common (may affect more than 1 in 10 people):

• decreased appetite
• low white blood cell count
• low levels of albumin in the blood (hypoalbuminemia)
• swelling of the lower legs or hands (peripheral oedema)
• weight loss
• fever (pyrexia)

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

• indigestion (dyspepsia)
• increased salivation (hypersalivation)
• increased blood pressure (hypertension)
• chills

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You may also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vyloy

The doctor, pharmacist or nurse is responsible for storing this medicine and for the proper disposal of any unused product. The following information is intended for healthcare professionals.
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 on the label of the vial after "Exp./EXP". The expiry date refers to the last day of that month.
Store in the refrigerator (2 ºC–8 ºC). Do not freeze. Keep in the original packaging to protect from light.
Do not store any unused portion from the single-dose vials for later use. Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What Vyloy contains

• The active substance is zolbetuximab.
• A vial of 100 mg of powder for concentrate for solution for infusion contains 100 mg of zolbetuximab.
• A vial of 300 mg of powder for concentrate for solution for infusion contains 300 mg of zolbetuximab.
• After reconstitution, each mL of solution contains 20 mg of zolbetuximab.
• The other components are arginine, phosphoric acid (E 338), sucrose and polysorbate 80 (E 433) (see section 2 “Vyloy contains polysorbate 80”). Description of the appearance of Vyloy and contents of the pack Vyloy powder for concentrate for solution for infusion is a lyophilized powder, white to off-white.

Vyloy is supplied in a carton containing 1 or 3 glass vials.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Astellas Pharma Europe B.V.
Sylviusweg 62
2333 BE Leiden
The Netherlands
Manufacturer
Astellas Ireland Co. Limited
Killorglin
Co Kerry
V93 FC86
Ireland
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
Astellas Pharma B.V. Branch Astellas Pharma d.o.o.
Tél/Tel: +32 (0) 2 5580710 Tel: +370 37 408 681
България Luxembourg/Luxemburg
Астелас Фарма ЕООД Astellas Pharma B.V. Branch
Teл.: +359 2 862 53 72 Belgique/Belgien
Tél/Tel: +32 (0)2 5580710
Česká republika Magyarország
Astellas Pharma s.r.o. Astellas Pharma Kft.
Tel: +420 221 401 500 Tel.: +36 1 577 8200
Danmark Malta
Astellas Pharma a/s Astellas Pharmaceuticals AEBE
Tlf.: +45 43 430355 Tel: +30 210 8189900
Deutschland Nederland
Astellas Pharma GmbH Astellas Pharma B.V.
Tel: +49 (0)89 454401 Tel: +31 (0)71 5455745
Eesti Norge
Astellas Pharma d.o.o. Astellas Pharma
Tel: +372 6 056 014 Tlf: +47 66 76 46 00
Ελλάδα Österreich
Astellas Pharmaceuticals AEBE Astellas Pharma Ges.m.b.H.
Τηλ: +30 210 8189900 Tel: +43 (0)1 8772668
España Polska
Astellas Pharma S.A. Astellas Pharma Sp.z.o.o.
Tel: +34 91 4952700 Tel.: +48 225451 111
France Portugal
Astellas Pharma S.A.S. Astellas Farma, Lda.
Tél: +33 (0)1 55917500 Tel: +351 21 4401300
Hrvatska România
Astellas d.o.o S.C. Astellas Pharma SRL
Tel: +385 1670 0102 Tel: +40 (0)21 361 04 95
Ireland Slovenija
Astellas Pharma Co., Ltd. Astellas Pharma d.o.o
Tel: +353 (0)1 4671555 Tel: +386 14011400
Ísland Slovenská republika
Vistor hf Astellas Pharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 4444 2157
Italia Suomi/Finland
Astellas Pharma S.p.A. Astellas Pharma
Tel: +39 (0)2 921381 Puh/Tel: +358 (0)9 85606000
Κύπρος Sverige
Ελλάδα Astellas Pharma AB
Astellas Pharmaceuticals AEBE Tel: +46 (0)40-650 15 00
Τηλ: +30 210 8189900
Latvija
Astellas Pharma d.o.o.
Tel: +371 67 619365
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/.

The following information is intended for healthcare professionals only:

Traceability
To improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly documented.

Instructions for preparation and administration
Reconstitution in the single-dose vial

• Follow appropriate handling and disposal procedures for antineoplastic medicinal products.
• Use appropriate aseptic technique when reconstituting and preparing solutions.
• Calculate the recommended dose based on the patient’s body surface area to determine the number of vials required.
• Reconstitute each vial as described below. If possible, direct the stream of sterile water for injection (SWFI) against the vial walls and not directly onto the lyophilized powder:
  a. 100 mg vial: slowly add 5 mL of SWFI to obtain a solution containing 20 mg/mL of zolbetuximab.
  b. 300 mg vial: slowly add 15 mL of SWFI to obtain a solution containing 20 mg/mL of zolbetuximab.
• Gently rotate each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to stand. Visually inspect the solution until air bubbles disappear. Do not shake the vial(s).
• Visually inspect the solution for particulate matter and discoloration. The reconstituted solution should be clear to slightly opalescent, colorless to slightly yellow, and free of visible particles. Discard any vial showing visible particles or discoloration.
• Based on the calculated dose volume, the reconstituted solution in the vial(s) must be immediately transferred into an infusion bag. This product contains no preservatives.

Dilution in the infusion bag

• Withdraw the calculated dose volume of reconstituted solution from the vial(s) and transfer it into an infusion bag.
• Dilute with sodium chloride 9 mg/mL (0.9%) solution for infusion. The size of the infusion bag should allow sufficient diluent to be added to achieve a final zolbetuximab concentration of 2 mg/mL. The diluted solution for zolbetuximab administration is compatible with intravenous infusion bags made of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with plasticizer [di(2-ethylhexyl) phthalate (DEHP) or trioctyl trimellitate (TOTM)], ethylene-propylene copolymer, ethylene-vinyl acetate (EVA) copolymer, styrene-ethylene-butylene-styrene copolymer, or glass (administration vial), and with infusion lines made of PE, polyurethane (PU), PVC with plasticizer [DEHP, TOTM or di(2-ethylhexyl) terephthalate], polybutadiene (PB), or modified PP elastomer, equipped with in-line filter membranes (pore size 0.2 μm) made of polyethersulfone (PES) or polysulfone.
• Mix the diluted solution by gentle inversion. Do not shake the bag.
• Before use, visually inspect the infusion bag for particulate matter. The diluted solution must be free of visible particles. Do not use the infusion bag if particulate matter is observed.
• Discard any unused residual solution remaining in the single-dose vials.

Administration

• Do not administer other medicinal products through the same infusion line.
• Administer the infusion immediately over a period of at least 2 hours via an intravenous line. Do not administer as an intravenous push or bolus. No incompatibilities have been observed with closed-system transfer devices made of PP, PE, stainless steel, silicone (rubber/oil/resin), polyisoprene, PVC with plasticizer [TOTM], acrylonitrile-butadiene-styrene (ABS) copolymer, methyl methacrylate-ABS copolymer, thermoplastic elastomer, polytetrafluoroethylene, polycarbonate, PES, acrylic copolymer, polybutylene terephthalate, PB, or EVA copolymer. No incompatibilities have been observed with central ports made of silicone rubber, titanium alloy, or PVC with plasticizer [TOTM].
• The use of in-line filters (pore size 0.2 μm with materials listed above) is recommended during administration.

Disposal
Vyloy is for single use only.
Any unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.