Takhzyro 300 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

TAKHZYRO 300 mg solution for injection in pre-filled syringe

lanadelumab

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if the side effects are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What TAKHZYRO is and what it is used for
2. What you need to know before using TAKHZYRO
3. How to use TAKHZYRO
4. Possible side effects
5. How to store TAKHZYRO
6. Contents of the pack and other information
7. Instructions for use

1. What TAKHZYRO is and what it is used for

TAKHZYRO contains the active substance lanadelumab.

What TAKHZYRO is used for

TAKHZYRO is a medicine used in patients 2 years of age and older with hereditary angioedema (HAE) to prevent angioedema attacks.

What is hereditary angioedema (HAE)

HAE is an inherited disease within a family. In people with this disease, there is either not enough of a protein called "C1 inhibitor" in the blood, or the C1 inhibitor does not work properly. This leads to an excess of "plasma kallikrein", which in turn causes higher levels of "bradykinin" in the bloodstream. Too much bradykinin causes symptoms of HAE, such as swelling and pain in:

• the hands and feet
• the face, eyelids, lips, or tongue
• the vocal cords (larynx), which can make it difficult to breathe
• the genitals

How TAKHZYRO works

TAKHZYRO is a type of protein that blocks the activity of plasma kallikrein, helping to reduce the amount of bradykinin in the bloodstream and thereby preventing HAE symptoms.

2. What you need to know before using TAKHZYRO

Do not use TAKHZYRO

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

Warnings and precautions

• Consult your doctor, pharmacist, or nurse before starting to use TAKHZYRO.
• If you experience a severe allergic reaction to TAKHZYRO with symptoms such as rash, chest tightness, wheezing, or rapid heartbeat, inform your doctor, pharmacist, or nurse immediately.

Keeping a record

It is strongly recommended that each time a dose of TAKHZYRO is administered, you record the name and batch number of the medicine, so that you have a record of the batches used.

Laboratory tests

Inform your doctor if you are using TAKHZYRO before undergoing blood coagulation tests, as the presence of TAKHZYRO in the blood may interfere with certain laboratory tests and lead to inaccurate results.

Children and adolescents

The use of TAKHZYRO is not recommended in children under 2 years of age, as it has not been studied in this age group.

Other medicines and TAKHZYRO

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

It is not known that TAKHZYRO affects other medicines or is affected by other medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Information on the safety of using TAKHZYRO during pregnancy and breastfeeding is limited. As a precautionary measure, it is preferable to avoid using lanadelumab during pregnancy and breastfeeding. Your doctor will discuss with you the risks and benefits of receiving this medicine.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is none or negligible.

TAKHZYRO contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe; i.e., essentially “sodium-free”.

3. How to use TAKHZYRO

TAKHZYRO is supplied in single-use pre-filled syringes as a ready-to-use solution. A physician experienced in the management of patients with HAE will initiate and supervise your treatment.

Follow exactly the instructions for administering the medicine provided in this leaflet or as directed by your doctor, pharmacist, or nurse. If you have any doubts or further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

How much TAKHZYRO to use

For adults and adolescents aged 12 years to under 18 years of age:

• The recommended starting dose is 300 mg of lanadelumab every 2 weeks. If you have had no attacks over a prolonged period of time, your doctor may adjust your dose to 300 mg of lanadelumab every 4 weeks, especially if your body weight is low.
• In patients with a body weight below 40 kg, a starting dose of 150 mg of lanadelumab every 2 weeks may also be considered. If you have had no attacks over a prolonged period of time, your doctor may change the dose to 150 mg of lanadelumab every 4 weeks.

For children aged 2 years to under 12 years of age, the recommended starting dose is based on body weight:

Body weight (kg)	Recommended starting dose	Dose adjustment
10 to less than 20 kg	150 mg of lanadelumab every 4 weeks	Dose increase to 150 mg of lanadelumab every 3 weeks may be considered in patients with inadequate attack control
20 to less than 40 kg	150 mg of lanadelumab every 2 weeks	Dose reduction to 150 mg of lanadelumab every 4 weeks may be considered in stable patients without breakthrough attacks on treatment
40 kg or more	300 mg of lanadelumab every 2 weeks	Dose reduction to 300 mg of lanadelumab every 4 weeks may be considered in stable patients without breakthrough attacks on treatment

• In patients with a body weight of 20 to less than 40 kg who have not had any attacks for a prolonged period of time, the physician may allow your child or the child in your care to continue receiving the same dose upon reaching 12 years of age.

How to inject TAKHZYRO

If you self-inject TAKHZYRO or if a caregiver administers it, you or your caregiver must read and carefully follow the instructions in section 7, "Instructions for Use".

• TAKHZYRO is injected under the skin ("subcutaneous injection").
• The injection may be administered by you or a caregiver in patients aged 12 years and older.
• The injection may be administered by a healthcare professional or a caregiver in patients aged 2 years to less than 12 years of age.
• A doctor, pharmacist, or nurse must train you to properly prepare and inject TAKHZYRO before you use it for the first time. Do not inject it yourself or administer it to another person until you have been trained to inject the medicine.
• Insert the needle into the fatty tissue of the stomach (abdomen), thigh, or upper arm.
• Inject the medicine at a different site each time.
• Use each TAKHZYRO pre-filled syringe only once.

If you use more TAKHZYRO than you should

Inform your doctor, pharmacist, or nurse if you have administered a dose of TAKHZYRO higher than recommended.

If you forget to use TAKHZYRO

If you miss a dose of TAKHZYRO, inject the missed dose as soon as possible. Administration of subsequent doses may require adjustment based on the desired dosing frequency, ensuring that:

• at least 10 days elapse between doses for patients on a once every 2 weeks dosing regimen,
• at least 17 days elapse between doses for patients on a once every 3 weeks dosing regimen,
• at least 24 days elapse between doses for patients on a once every 4 weeks dosing regimen.

If you are unsure about when to inject TAKHZYRO after missing a dose, consult your doctor, pharmacist, or nurse.

If you stop using TAKHZYRO

It is important that you continue to inject TAKHZYRO as directed by your doctor, even if you feel better. If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

If you have a severe allergic reaction to TAKHZYRO with symptoms such as rash, chest tightness, wheezing, or rapid heartbeat, inform your doctor, pharmacist, or nurse immediately.

Tell your doctor, pharmacist, or nurse if you notice any of the following adverse effects.

Very common (may affect more than 1 in 10 people):

• Reactions at the injection site: symptoms include pain, redness, bruising, discomfort, swelling, bleeding, itching, skin hardening, tingling, warmth, and rash.

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

• Allergic reactions, such as itching, discomfort, and tingling of the tongue
• Dizziness, feeling faint
• Raised skin rash
• Muscle pain
• Abnormal laboratory test results showing changes in the liver

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of TAKHZYRO

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and on the carton after EXP. The expiry date refers to the last day of the month indicated.

TAKHZYRO 300 mg solution for injection in a pre-filled syringe

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Keep the pre-filled syringe in the outer packaging to protect it from light.

Pre-filled syringes may be stored below 25 °C for a single period of up to 14 days, but not beyond the expiry date.

After storage at room temperature, do not return TAKHZYRO to the refrigerator for storage.

When a pre-filled syringe is removed from a multi-pack container, the remaining pre-filled syringes should be returned to the refrigerator for future use.

Do not use this medicine if there are signs of deterioration, such as particles in the pre-filled syringe or a change in colour of the injection solution.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the container and other information

Composition of TAKHZYRO

• The active substance is lanadelumab. Each pre-filled syringe contains 300 mg of lanadelumab in a 2 ml solution.
• The other components are disodium phosphate dihydrate, citric acid monohydrate, histidine, sodium chloride, polysorbate 80, and water for injections; see section 2 "TAKHZYRO contains sodium".

Appearance of the product and contents of the container

TAKHZYRO is a clear, colourless to pale yellow injectable solution in a pre-filled syringe.

TAKHZYRO is available as:

• a single pack containing one 2 ml pre-filled syringe in a box
• a single pack containing two 2 ml pre-filled syringes in a box
• multiple packs containing 3 intermediate boxes, each containing two 2 ml pre-filled syringes.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland

Manufacturer

Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland

Shire Pharmaceuticals Ireland Limited
Blocks 2 & 3 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
Ireland

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium Takeda Belgium NV Tel/Tel: +32 2 464 06 11 [email protected]	Lithuania Takeda, UAB Tel: +370 521 09 070 [email protected]
	Luxembourg/Luxembourg Takeda Belgium NV Tel/Tel: +32 2 464 06 11 [email protected]
Czech Republic Takeda Pharmaceuticals Czech Republic s.r.o. Tel: + 420 234 722 722 [email protected]	Hungary Takeda Pharma Kft. Tel.: +36 1 270 7030 [email protected]
Denmark Takeda Pharma A/S Tlf: +45 46 77 10 10 [email protected]	Malta Drugsales Ltd Tel: +356 21419070 [email protected]
Germany Takeda GmbH Tel: +49 (0)800 825 3325 [email protected]	Netherlands Takeda Nederland B.V. Tel: +31 20 203 5492 [email protected]
Estonia Takeda Pharma OÜ Tel: +372 6177 669 [email protected]	Norway Takeda AS Tlf.: +47 800 800 30 [email protected]
Greece Takeda ELLAS S.A. Tel: +30 210 6387800 [email protected]	Austria Takeda Pharma Ges.m.b.H. Tel: +43 (0) 800-20 80 50 [email protected]
Spain Takeda Farmacéutica España, S.A. Tel: +34 917 90 42 22 [email protected]	Poland Takeda Pharma Sp. z o.o. Tel.: +48223062447 [email protected]
France Takeda France SAS Tel: + 33 1 40 67 33 00 [email protected]	Portugal Takeda Farmacêuticos Portugal, Lda. Tel: + 351 21 120 1457 [email protected]
Croatia Takeda Pharmaceuticals Croatia d.o.o. Tel: +385 1 377 88 96 [email protected]	Romania Takeda Pharmaceuticals SRL Tel: +40 21 335 03 91 [email protected]
Ireland Takeda Products Ireland Ltd Tel: 1800 937 970 [email protected]	Slovenia Takeda Pharmaceuticals farmacevtska družba d.o.o. Tel: + 386 (0) 59 082 480 [email protected]
Iceland Vistor ehf. Tel: +354 535 7000 [email protected]	Slovakia Takeda Pharmaceuticals Slovakia s.r.o. Tel: +421 (2) 20 602 600 [email protected]
Italy Takeda Italia S.p.A. Tel: +39 06 502601 [email protected]	Finland/Finland Takeda Oy Tel/Tel: 0800 774 051 [email protected]
Cyprus Proton Medical (Cyprus) Ltd Tel: +357 22866000 [email protected]	Sweden Takeda Pharma AB Tel: 020 795 079 [email protected]
Latvia Takeda Latvia SIA Tel: +371 67840082 [email protected]	United Kingdom (Northern Ireland) Takeda UK Ltd Tel: +44 (0) 3333 000 181 [email protected]

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

1. Instructions for use

Be sure to read, understand, and follow the instructions for use before injecting TAKHZYRO. Contact your healthcare professional if you have any questions.

Intended use

The TAKHZYRO pre-filled syringe is a single-use, ready-to-use, fixed-dose (300 mg/2 ml) needle injection device intended for subcutaneous administration by healthcare professionals and caregivers or for self-administration (for patients aged 12 years and older).

Storage of TAKHZYRO

• Store the TAKHZYRO pre-filled syringe in the refrigerator at 2 °C to 8 °C. Do not freeze.
• A pre-filled syringe removed from refrigeration must be stored at less than 25 °C and used within 14 days. After storage at room temperature, do not re-refrigerate TAKHZYRO for storage purposes.
• When a pre-filled syringe is removed from a multi-pack container, the remaining pre-filled syringes should be returned to the refrigerator for future use.
• Store TAKHZYRO in the original carton to protect the pre-filled syringe from light.
• Discard the TAKHZYRO pre-filled syringe if it has not been refrigerated, has been frozen, or has not been stored in its original packaging protected from light.
• Do not shake TAKHZYRO.
• Keep TAKHZYRO and all medicines out of the reach of children.

Parts of your TAKHZYRO pre-filled syringe before use (Figure A).

Figure A: TAKHZYRO pre-filled syringe

STEP 1: Preparing the injection

1. Take an alcohol wipe, gauze pad or cotton ball, adhesive bandage, and a sharps disposal container (Figure B) and place them all on a clean, flat surface in a well-lit area. These items are not included in the TAKHZYRO package.

Figure B: Supplies

1. Remove the TAKHZYRO pre-filled syringe from the refrigerator.
   • Do not use the TAKHZYRO pre-filled syringe if the security seal is open or broken.
   • Before preparing the injection, wait for the pre-filled syringe to reach room temperature for at least 15 minutes.
   • This medicine is heat-sensitive. Do not use heat sources such as a microwave or hot water to warm the TAKHZYRO pre-filled syringe.
   • Do not remove the needle cap until you are ready to begin the injection.

1. Open the carton. Hold the syringe barrel and remove the TAKHZYRO pre-filled syringe from the tray (Figure C).

Figure C: Remove the pre-filled syringe

1. Wash your hands with water and soap (FigureD). Dry your hands completely.

• Do not touch any surface or part of the body after washing your hands before starting the injection.

Figure D: Hand washing

1. Check the expiration date (EXP) on the barrel of the syringe (Figure E).

Do not use the TAKHZYRO pre-filled syringe if the expiration date has passed. If the TAKHZYRO pre-filled syringe is expired, dispose of it in a sharps container and contact your healthcare professional.

Figure E: Location of the expiration date

1. Inspect the TAKHZYRO pre-filled syringe to ensure it is not damaged and confirm that the medicine is colorless or pale yellow (Figure F).
   • Do not use the product if the syringe is damaged, for example, if it has cracks.
   • Do not use the TAKHZYRO pre-filled syringe if the medicine has discolored, appears cloudy, or contains particles or deposits.
   • You may see air bubbles in your TAKHZYRO pre-filled syringe. This is normal and will not affect the dose.

If you cannot use the pre-filled syringe, contact your healthcare professional.

Figure F: Examine the prefilled syringe

STEP 2: Selection and preparation of the injection site

1. The TAKHZYRO pre-filled syringe should only be injected in the following areas (Figure G):

• stomach (abdomen)
• thigh
• upper arm (only if the injection is administered by a healthcare professional or caregiver)
  • Do not administer the injection in an area of skin that is irritated, red, infected, or bruised.
  • The chosen injection site must be at least 5 cm away from any scar or the navel.

Important:

Rotate injection sites to maintain healthy skin. Each new injection should be administered at least 3 cm away from the previous injection site.

1. Clean the injection site with an alcohol wipe and wait for it to dry completely (Figure H).
   • Do not blow on or fan the cleaned area.
   • Do not touch this area again before administering the injection.

Figure H: Clean the injection site

1. Carefully pull off the needle cap with one hand while firmly holding the center of the TAKHZYRO pre-filled syringe with the other hand. Discard the needle cap in the trash or in a sharps container (FigureI).
   • Do not touch or press the plunger until you are ready to begin the injection.
   • To avoid needle-stick injury, do not recap the TAKHZYRO pre-filled syringe.
   • Do not use the TAKHZYRO pre-filled syringe if it has been dropped without the needle cap.
   • Do not use the TAKHZYRO pre-filled syringe if the needle appears damaged or bent.
   • Do not touch the needle or allow the needle to come into contact with anything.

FigureI: Removing the needle cap

STEP3: Injecting TAKHZYRO

1. Hold the TAKHZYRO pre-filled syringe in one hand as you would hold a pencil (FigureJ). Avoid touching the needle or pushing the plunger.

FigureJ: Holding the pre-filled syringe

1. With your other hand, gently pinch the skin to create a 3-cm (approximately 1-inch) skin fold at the cleaned injection site.

• Maintain the skin fold until the injection is complete and the needle has been withdrawn (FigureK).

Figure K: Pinch a 3cm skin fold

1. With a short and quick motion, insert the needle into the skin at an angle of 45 to 90 degrees. Make sure you keep the needle in place (FigureL).

Important: Inject directly into the fatty tissue under the skin (subcutaneous injection).
Figure L: Inserting the needle

1. Slowly push the plunger until it stops (Figure M).
2. Slowly remove the needle while keeping the syringe at the same angle. Carefully release the skin fold.

Important: Do not remove the needle until all the liquid has been injected and the syringe is empty.
	Figure M: Push the plunger until it stops

When the injection is complete, the plunger will be at the bottom of the syringe barrel (Figure N).
Figure N: Plunger at the bottom of the syringe barrel

Press the cotton swab or gauze pad against the injection site, if needed, and hold for 10 seconds. Do not rub the injection site. You may have slight bleeding. This is normal. Cover the injection site with an adhesive bandage, if needed. Dispose of the used TAKHZYRO pre-filled syringe. Place the used TAKHZYRO pre-filled syringe into a sharps disposal container immediately after use (FigureO). To avoid needle-stick injuries, do not recap the needle. Do not reuse the TAKHZYRO pre-filled syringe or any other injection materials. Do not touch the needle. Important: Always keep the sharps disposal container out of the reach of children.

FigureO: Dispose in a sharps disposal container