Tretten: Uses, Side Effects and Dosage

What is Tretten^® used for?

Tretten^® is recombinant blood coagulation Factor XIII A-subunit. Tretten^® is used to prevent bleeding in patients who do not have enough Factor XIII A-subunit.

How does Tretten^® work?

Tretten^® replaces the missing Factor XIII A-subunit and helps to stabilize the initial blood clot.

What are the ingredients in Tretten^®?

Medicinal ingredients: The medicinal ingredient is recombinant Factor XIII A-subunit (catridecacog).

Non-medicinal ingredients: L-histidine, polysorbate 20, sodium chloride, and sucrose.

Tretten^® comes in the following dosage forms:

Tretten^® comes as a freeze-dried powder containing 2500 IU/vial (corresponding to 15 mg/vial). The powder in the vial is reconstituted (dissolved) with the solvent (sterile water) that is supplied with your Tretten^®. After reconstitution, 1 mL of solution contains 833 IU of catridecacog (corresponding to 5 mg/mL).

Do not use Tretten^® if:

Do not use Tretten^® if you are allergic (hypersensitive) to catridecacog or to any ingredient in the formulation or component of the container.

Do not use Tretten^® without talking to your doctor, if you are pregnant, planning to become pregnant, or are breast feeding.

Other warnings you should know about:

Once you have prepared Tretten^® for injection it should be used immediately. For proper storage instructions see “How to take Tretten^®” and “Storage”.

BEFORE you use Tretten^® talk to your doctor if you have, or have ever had any of the following:

• A higher risk of blood clots forming (thrombosis), as Tretten^® may increase the severity of a pre-existing clot.
• Liver damage.
• Experienced unexpected spontaneous bleeding during treatment with Factor XIII containing products. Antibodies against Tretten^® could decrease the effectiveness of the treatment and thereby result in unexpected spontaneous bleeding episodes. Contact your doctor immediately if bleeding occurs.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with Tretten^®:

Please tell your doctor if you are using or have recently used any other medicines, including medicines obtained without a prescription.

Do not use Tretten^® and rFVIIa (another blood clotting factor) together.

How to take Tretten^®:

Always use Tretten^® exactly as your doctor has told you. You should check with your doctor if you are not sure.

Tretten^® is given as an injection into a vein. For instructions on how to prepare and administer Tretten^® please refer to the sections ‘Preparing Your Injection’ and ‘Giving Your Injection’ located at the end of this insert.

Once you have prepared Tretten^® for injection it should be used immediately. This is because if not stored correctly, the medicine may no longer be sterile. Also, the amount of activated Factor XIII in the medicine may increase. Activated Factor XIII may increase the severity of a pre-existing blood clot. It is therefore important that you store Tretten^® according to the storage instructions below.

PREPARING YOUR INJECTION

To reconstitute and administer this product you will need the following tools: 10 mL syringe or size of syringe as most convenient according to injection volume, alcohol swabs, the vial adapter included, and an infusion set (tubing, butterfly needle). Check the name and the colour of the package to make sure it contains the right product. Also check that the product has not passed the expired date. Reconstitute only with the solvent provided with Tretten® (sterile water for injection). Always use sterile technique. Before starting, wash your hands with soap and water and dry with a clean towel. Bring the powder and solvent vials to room temperature, but

not above 25°C. You can do this by holding the vials in your hands until they feel as warm as your hands. Remove the plastic caps from the two vials. If the caps are loose or missing, do not use the vials. Clean the rubber stoppers on the vials with alcohol swabs and allow them to dry prior to use. Do not touch the rubber stoppers after wiping them.
Step A		The product is reconstituted using the vial adapter included. Remove the protective paper from the vial adapter, without taking the vial adapter out of the protective cap. If the protective paper is not fully sealed or if it is broken, do not use the vial adapter. Place the solvent vial on a flat and solid surface and attach the vial adapter to the solvent vial (sterile water for injection). Take care not to touch the spike on the vial adapter.
Step B		Once attached, remove the protective cap from the vial adapter by lightly squeezing the protective cap with your thumb and index finger.
Step C		Pull the plunger to draw in a volume of air that is equal to the amount of solvent in the solvent vial (3.2 mL sterile water).

Step D		Screw the syringe tightly onto the vial adapter on the solvent vial. Inject air into the vial by pushing the plunger until you feel a clear resistance.
Step E		Hold the syringe with the solvent vial upside down. Pull the plunger to draw the solvent into the syringe.
Step F		Remove the empty solvent vial by tipping the syringe with the attached vial adapter.
Step G		Click the vial adapter, still attached to the syringe onto the powder vial. Hold the syringe slightly tilted with the vial facing downwards. Push the plunger slowly to inject the solvent into the powder vial. Make sure not to aim the stream of solvent directly at the powder as this will cause foaming.

Step H		Gently swirl the vial until all the powder is dissolved. Do not shake the vial as this will cause foaming. Check the solution for bits and discolouration. If you notice either, do not use it. The reconstituted product is a clear to slightly opalescent and colourless solution. If you need a larger dose, repeat the procedure in a separate syringe until you have reached your required dose.
	Special Additional Instructions for Patients Weighing Less than 24 kg If the body weight is less than 24 kg, the reconstituted Tretten® should be diluted with 6.0 mL of 0.9% sodium chloride solution for injection. Your doctor will let you know if this is the case, and instruct you on how to dilute Tretten®. To dilute the reconstituted Tretten® the following tools are needed: a vial containing 0.9% sodium chloride solution for injection, a 10 mL syringe and alcohol swabs. General Instructions for Dilution: The dilution should be performed using sterile technique. Carefully draw exactly 6.0 mL of 0.9% sodium chloride solution for injection into the 10 mL syringe. Slowly inject the 6.0 mL of 0.9% sodium chloride solution for injection into the reconstituted Tretten® vial. Gently swirl the vial to mix the solution. The diluted solution is a clear to slightly opalescent andcolourless solution. Check the injection solution for particles and for discolouration. If either is noticed, please discard. After dilution proceed to the step ‘GIVING YOUR INJECTION’. Important Information Once you have prepared Tretten® it should be used immediately. This is because if left, the medicine may no longer be sterile. Also, the amount of activated Tretten® in the medicine will increase. Activated Tretten® may increase your risk of getting a blood clot (thrombosis). If the reconstituted product is not used immediately, it should be used within 3 hours of reconstitution, and can be stored at room temperature during this period. Any unused product stored at room temperature for 3 hours should be discarded. Alternatively, if the reconstituted product is not administered immediately, it should be stored in the refrigerator at 2°C - 8°C for no longer than 24 hours. After this period the product should be discarded.

Usual dose:

• Your dose will depend on how much you weigh.
• The usual dose is 35 IU for each kilogram of body weight.
• The injections are given once a month.

Overdose:

There is limited information on overdosing with Tretten^®. None of the reported cases have had a medical consequence. If you have injected more Tretten^® than you should, talk to your doctor immediately.

Missed dose:

If you forget an injection of Tretten^® talk to your doctor immediately. Do not take a double dose to make up for a forgotten dose.

Stopping your treatment:

If you stop using Tretten^® you are not protected against bleeding. Do not stop using Tretten^® without talking to your doctor. Your doctor will explain what might happen if you stop treatment and will discuss other options with you.

What are possible side effects from using Tretten^®?

These are not all the possible side effects you may have when taking Tretten^®. If you experience any side effects not listed here, tell your healthcare professional.

If you have an allergic reaction, see a doctor immediately. The signs may include:

• Hives
• Itching
• Swelling
• Difficulty breathing
• Low blood pressure (paleness and coldness of skin, rapid heartbeat)
• Feeling dizzy and sweating

The following is not a complete list of side effects. For any unexpected effects while taking Tretten^®, contact your doctor.

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

Storage:

• Do not use Tretten^® after the expiry date which is stated on the label and the outer carton
• Store in the original package in order to protect from light
• Store in a refrigerator
• Do not freeze

It is recommended to use the reconstituted product immediately.

If the reconstituted product is not used immediately, it should be used within 3 hours of reconstitution, and can be stored at room temperature during this period. Any unused product stored at room temperature for 3 or more hours should be discarded.

Alternatively, if the reconstituted product is not administered immediately, it should be stored in the refrigerator at 2°C - 8°C for no longer than 24 hours. After this period the product should be discarded.

If the product is diluted with 0.9% sodium chloride solution for injection (for those patients weighing less than 24 kg), the storage and stability recommendations specified above are still applicable.

Do not freeze reconstituted Tretten^® or store it in syringes.

Keep out of the reach and sight of children.

If you want more information about Tretten^®:

If you still have questions or would like more information, please contact your doctor.

This document plus the full product monograph, prepared for health professionals can be found at:

http://www.novonordisk.ca or by contacting Novo Nordisk Canada Inc., at: 1-800-465-4334.

Tretten^® is a registered trademark of Novo Nordisk Health Care AG and is used under license by Novo Nordisk Canada Inc.

© 2024

Novo Nordisk Canada Inc.

Last revised: September 24, 2024