VEYVONDI 650 IU POWDER AND SOLVENT FOR SOLUTION FOR INJECTION - patient leaflet, side effects, dosage

VEYVONDI

Patients developing inhibitors

Inhibitors (antibodies) against the VWF may occur in some patients receiving the medicine.These inhibitors, especially at high levels, could cause the treatment to stop working properly. You will be monitored carefully for the possibility of having developed these inhibitors.

– If your bleeding is not controlled with VEYVONDI, tell your doctor immediately.

If your plasma VWF or factor VIII fail to reach the expected levels with VEYVONDI based on the test results followed by your doctor, or if bleeding is not adequately controlled, it could be due to the presence of VWF or factor VIII antibodies. This will be checked by your doctor. You might need a higher dose of VEYVONDI, or a higher dose of factor VIII, or even a different medicine to control bleedings. Do not increase the total dose of VEYVONDI to control your bleeding without consulting your doctor.

If you have previously been treated with plasma-derived VWF concentrates you may have reduced response to VEYVONDI due to pre-existing antibodies. Your doctor may adjust the dose according to your laboratory results.

Thrombolism and embolism

There is a risk of occurrence of thrombotic events if you have known clinical or laboratory risk factors.Therefore your doctor will monitor you for early signs of thrombosis.

FVIII products may contain varying amounts of VWF. Therefore, any FVIII product that would be administered in combination with VEYVONDI should be a pure FVIII product.

If you previously had problems with blood clots or vessel occlusion (thromboembolic complications), tell your doctor immediately.

Children and adolescents

VEYVONDI is not approved for use in children or adolescents below 18 years.

Other medicines and VEYVONDI

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

VEYVONDI is not likely to affect your ability to drive and use machines.

VEYVONDI contains sodium

This medicine contains 5.2 mg sodium in each 650 IU vial or 10.4 mg sodium in each 1300 IU vial.

This is equivalent to 2.2% of the recommended maximum daily dietary intake of sodium for an adult, assuming 70 kg body weight and 80 IU/kg body weight.

This should be taken into consideration if you are on a controlled sodium diet.

3.How to use VEYVONDI

Your treatment with VEYVONDI will be supervised by a doctor who is experienced in the care of patients with von Willebrand disease.

Your doctor will calculate your dose of VEYVONDI (in international units or IU). The dose depends on: – body weight,

• – the site of the bleeding

• – intensity of the bleeding,

• – your clinical condition,

• – the required surgery

• – the VWF activity levels in your blood after surgery

• – the severity of your disease

Your doctor may test your blood to make sure that you have adequate levels of von Willebrand factor. This is particularly important if you are having major surgery.

Treatment of bleeding episodes

Your doctor will calculate the dose that is most appropriate for you, how often you should receive VEYVONDI and for how long.

For minor bleeding (e.g. nose bleed, oral bleeding, menorrhagia), each initial dose is usually 40 to 50 IU/kg and for major bleeding (severe or refractory nose bleed, menorrhagia, gastrointestinal bleeding, Central nervous system trauma, haemarthrosis, or traumatic haemorrhage), each initial dose is 50 to 80 IU/kg. Subsequent doses (as clinically required) are 40 to 50 IU/kg every 8 to 24 hours for minor bleeds as long as deemed clinically necessary and for major bleeds 40 to 60 IU/kg for approximately 2–3 days.

If you feel that VEYVONDI is not working well enough, talk to your doctor. Your doctor will perform tests to make sure that you have adequate levels of von Willebrand factor. If you use VEYVONDI at home, your doctor will make sure that you are shown how to infuse it and how much to use.

Prevention of bleeding in case of elective surgery

For prevention of excessive bleeding your doctor will assess the FVIII:C levels within 3 hours before surgery. If your FVIII level is inadequate your doctor may give you a dose of 40–60 IU/kg VEYVONDI 12–24 hours (pre-operative dose) prior to initiating elective surgery in order to raise FVIII levels to the target level (0.4 IU/mL for minor and at least 0.8 IU/mL for major surgery). Within 1 hour prior to surgery, you will receive a dose of VEYVONDI based on the assessment 3 hours before surgery. The dose depends on VWF and FVIII levels of the patient, the type and severity of the expected bleeding.

How VEYVONDI is given

VEYVONDI is usually infused into a vein (intravenously) by your doctor or nurse. Detailed instructions for reconstitution and administration are given at the end of this package leaflet.

Use in children and adolescents

VEYVONDI is not approved for use in children and adolescents below 18 years.

If you use more VEYVONDI than you should

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. If you infuse more VEYVONDI than recommended, tell your doctor as soon as possible. There may be a risk of developing blood clots (thrombosis) in case of an accidental high dose.

If you forget to use VEYVONDI

• – Do not infuse a double dose to make up for a forgotten dose.

• – Proceed with the next infusion as scheduled and continue as advised by your doctor.

If you stop using VEYVONDI

Do not stop using VEYVONDI without consulting your doctor.

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

4.Possible side effects

Like all medicines, this medicine may cause side effects, although not everybody gets them.

You can have a serious allergic reaction to VEYVONDI.

You must stop the infusion and contact your doctor immediately if you have any of the following early symptoms of severe allergic reactions:

• – rash or hives, itching all over the body,

• – tightness of the throat, chest pain or chest tightness, – difficulty breathing, light headedness, fast heartbeat, – dizziness, nausea or fainting.

Side effects that have been reported with VEYVONDI that can occur commonly (up to 1 in 10 patients) are: nausea, vomiting, tingling or burning at infusion site, chest discomfort, dizziness, vertigo, blood clots, hot flushes, itching, high blood pressure, muscle twitching, unusual taste, and increased heart rate.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme at Website: or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store VEYVONDI

• – 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 label after EXP. The expiry date refers to the last day of that month.

• – Do not store above 30°C.

• – Do not freeze.

• – Keep the vial in the outer carton in order to protect from light.

• – Do not refrigerate the solution after preparation.

• – Use the reconstituted product within 3 hours to avoid the risk of microbial contamination because the product does not contain preservatives.

• – This medicine is for single use only. Discard any unused solution appropriately.

• – Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.Contents of the pack and other information

What VEYVONDI contains

The active substance is vonicog alfa (recombinant human von Willebrand factor).

VEYVONDI 650 IU powder and solvent for solution for injection

Each vial of powder contains nominally 650 International Units (IU) vonicog alfa.

After reconstitution with the 5 mL solvent provided, VEYVONDI contains approximately 130 IU/mL vonicog alfa.

VEYVONDI 1300 IU powder and solvent for solution for injection

Each vial of powder contains nominally 1300 International Units (IU) vonicog alfa.

After reconstitution with the 10 mL solvent provided, VEYVONDI contains approximately 130 IU/mL vonicog alfa.

The other ingredients are:

• – Sodium citrate, glycine, trehalose dihydrate, mannitol, polysorbate 80 and water for injections.

• – See section 2 “VEYVONDI contains sodium”.

What VEYVONDI looks like and contents of

the pack

VEYVONDI is a white to off-white powder. After reconstitution, when drawn into the syringe, the solution is clear, colourless in appearance and free from flakes or other foreign particles.

Each pack of VEYVONDI 650 IU contains:

• – powder in a glass vial with a rubber stopper

• – 5 mL of solvent in a glass vial with a rubber stopper

• – one reconstitution device (Mix2Vial)

Each pack of VEYVONDI 1300 IU contains:

• – powder in a vial (type I glass), with a butyl rubber stopper

• – 10 mL of solvent in a vial (type I glass), with a rubber stopper (bromobutyl)

• – one reconstitution device (Mix2Vial)

Marketing Authorisation Holder

Baxalta Innovations GmbH

IndustriestraBe 67

1221 Vienna

Austria

Tel: +44(0)1256 894 959

e-mail:

Manufacturer

Takeda Manufacturing Austria AG

Industriestrasse 67

1221 Vienna

Austria

This leaflet was last revised in 01/2022.

Instructions for preparation and administration

General instructions

Check the expiry date, and ensure that the VEYVONDI powder and water for injections (solvent) are at room temperature prior to preparation. Do not use after the expiry date stated on the labels and carton.

Use antiseptic technique (clean and low-germ conditions) and a flat work surface during the reconstitution procedure. Wash your hands and put on clean exam gloves (the use of gloves is optional).

Use the reconstituted product (after mixing the powder with the supplied water) as soon as possible and within three hours. You can store the reconstituted product at room temperature not to exceed 25°C for up to three hours. Reconstituted product should not be refrigerated. Discard after three hours.

Ensure that the VEYVONDI powder vial and the Sterilised Water for Injections (solvent) are at room temperature prior to preparation.

Use plastic syringes with this product because proteins in the product tend to stick to the surface of glass syringes.

Do not mix VEYVONDI with other medicinal products except for rFVIII.

Instructions for reconstitution

	Steps	Image example
1	Remove the caps from the VEYVONDI powder and solvent vials to expose the centre of the rubber stoppers.
2	Disinfect each stopper with a separate sterile alcohol swab (or other suitable sterile solution suggested by your doctor or haemophilia treatment centre) by wiping the stopper for several seconds. Allow the rubber stoppers to dry. Place the vials on a flat surface.	© 0B
3	Open the Mix2Vial device package by completely peeling away the lid, without touching the inside of the package. Do not remove the Mix2Vial device from the package.	NA
4	Turn the package with the Mix2Vial device upside down and place it over the top of the solvent vial. Firmly insert the blue plastic spike of the device into the centre of the solvent vial stopper by pushing straight down. Grip the package at its edge and lift it off the Mix2Vial device. Be careful not to touch the clear plastic spike. The solvent vial now has the Mix2Vial device connected to it and is ready to be connected to the VEYVONDI vial.	4l _
5	To connect the solvent vial to the VEYVONDI vial, turn the solvent vial over and place it on top of the vial containing VEYVONDI concentrate. Fully insert the clear plastic spike into the VEYVONDI vial stopper by firmly pushing straight down. This should be done right away to keep the liquid free of germs. The solvent will flow into the VEYVONDI vial by vacuum. Check that all the solvent has transferred. Do not use if vacuum has been lost and the solvent does not flow into the VEYVONDI vial.	■ ■ ! ■ □< i Ji'/'
6	Gently and continuously swirl the connected vials or allow the reconstituted product to stand for 5 minutes then gently swirl to ensure the powder is completely dissolved. Do not shake. Shaking will adversely affect the product. Do not refrigerate after reconstitution.
7	Disconnect the two sides of the Mix2Vial from each other by holding the clear plastic side of the Mix2Vial device attached to the VEYVONDI vial with one hand and the blue plastic side of the Mix2Vial device attached to the solvent vial with the other hand. Turn the blue plastic side counterclockwise and gently pull the two vials apart. Do not touch the end of the plastic connector attached to the VEYVONDI vial containing the dissolved product. Place the VEYVONDI vial on a flat work surface. Discard the empty solvent vial.	'— ---

8	Draw air into the empty, sterile disposable plastic syringe by pulling back on the plunger. The amount of air should equal the amount of reconstituted VEYVONDI that you will withdraw from the vial.
9	Leaving the VEYVONDI vial (containing the dissolved product) on your flat work surface, connect the syringe to the clear plastic connector by attaching and turning the syringe clockwise.	Ad WiV
10	Hold the vial with one hand and use the other hand to push all the air from the syringe into the vial	/ tJf-
11	Flip connected syringe and VEYVONDI vial so the vial is on top. Be sure to keep the syringe plunger pressed in. Draw the VEYVONDI into the syringe by pulling plunger back slowly.	fk
12	Do not push and pull solution back and forth between syringe and vial. Doing so may harm the medicine. When ready to infuse, disconnect the syringe by turning it counterclockwise. Inspect the syringe visually for particulate matter; the solution in the syringe should be clear. If flakes or particles are seen, do not use the solution and notify your doctor.	J —
13	If you need more than one vial of VEYVONDI to make up your dose: Leave the syringe attached to the vial until an additional vial is prepared. Use the reconstitution steps above (2 to 8) to prepare the additional vial of VEYVONDI using a fresh Mix2Vial for each vial
14	The contents of two vials may be drawn into a single syringe. NOTE: When pushing air into a second vial of VEYVONDI to be pooled into a syringe, position the vial and connected syringe so that the vial is on top.

Instructions for administration

Inspect the prepared solution in the syringe for particulate matter and discoloration prior to administration (the solution should be clear, colourless and free from particles). It is not uncommon for a few flakes or particles to remain in the product vial after reconstitution. The filter included in the Mix2Vial device removes those particles completely. Filtration does not influence dosage calculations. The solution in the syringe should not be used if it is cloudy or contains flakes or particles after filtration.

• 1. Attach the infusion needle to a syringe containing VEYVONDI solution. For comfort, a winged (butterfly) infusion set is preferred. Point the needle up and remove any air bubbles by gently tapping the syringe with your finger and slowly and carefully pushing air out of the syringe and needle.

• 2. Apply a tourniquet and get the infusion site ready by wiping the skin well with a sterile alcohol swab (or other suitable sterile solution suggested by your doctor or haemophilia treatment centre).