Tretten

Tretten is a prescription medication used to prevent bleeding in people with a rare blood clotting disorder known as congenital Factor XIII A-subunit deficiency. This medication replaces an important protein necessary for normal clotting.

Tretten comes in an injectable form to be given directly into a vein (IV) by a healthcare professional. In some cases, patients can be taught to properly administer this medication.

Common side effects include headache and pain at the site of injection. 

• Novo Nordisk, Inc.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Tretten, there are no specific foods that you must exclude from your diet when receiving this medication.

Factor XIII is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

Factor XIII is usually given once every 4 weeks. Follow your doctor's dosing instructions very carefully.

Factor XIII is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Allow the mixture to reach room temperature before giving the injection. Do not heat the medicine before using.

Factor XIII should look clear or slightly yellow in color. Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription.

Do not mix factor XIII with other injectable medications in the same IV line.

Each single use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

While using factor XIII, you may need frequent blood tests.

Store unmixed factor XIII in the refrigerator, do not freeze. Keep the medicine in its original container.

Unopened vials of factor XIII may also be stored at room temperature for up to 6 months, away from moisture, heat, and light. Do not refrigerate an unopened vial that has been stored at room temperature.

After mixing factor XIII with a diluent, store at room temperature and use within 4 hours. Do not refrigerate or freeze.

Throw away any unused factor XIII after the expiration date on the label has passed.

Other drugs may interact with factor XIII, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

• Biosynthetic (recombinant DNA origin) preparation of human factor XIII A2 homodimer (consists of 2 factor XIII A-subunits).1 7 12

• Congenital factor XIII deficiency is a rare but serious bleeding disorder manifested by a lifelong bleeding tendency that typically includes umbilical bleeding during the neonatal period, delayed soft tissue bleeding, mucosal bleeding, poor wound healing, recurrent miscarriage, and intracranial hemorrhage.6 8 13 34 Predominantly caused by deficiency of the factor XIII A-subunit; factor XIII B-subunit deficiency is extremely rare and associated with milder clinical manifestations.6 8 13

• Patients with congenital factor XIII A-subunit deficiency have decreased plasma levels of endogenous factor XIII A-subunit, resulting in a hemorrhagic tendency.8 Factor XIII A-subunit (recombinant) restores normal clot solubility in such patients.7

• Factor XIII is a proenzyme (protransglutaminase) that is activated in the presence of calcium by thrombin; once activated, factor XIIIa promotes cross-linking of fibrin and other proteins (α2-plasmin inhibitor, fibrinogen, collagen) to strengthen and stabilize the fibrin clot, protect from fibrinolysis, and enhance platelet adhesion to the site of tissue injury.1 5 7 8 9

• Factor XIII circulates in plasma as a heterotetrameric glycoprotein consisting of 2 A-subunits and 2 B-subunits (A2B2).1 8 9 The A-subunit is the active catalytic domain; B-subunits function as carrier molecules for A-subunits.1

• Factor XIII A-subunit (recombinant) binds to free, noncomplexed factor XIII B-subunit to form A2B2.1 7 In its complexed form, pharmacodynamic and pharmacokinetic (e.g., half-life) properties of factor XIII A-subunit (recombinant) are similar to endogenous factor XIII.1 6 7 35

• Prepared using DNA technology in a yeast (Saccharomyces cerevisiae) expression system and further purified through several chromatography steps (e.g., hydrophobic interaction, ion exchange chromatography).1 Manufactured without any human or animal components.1

• Importance of advising patients to read the manufacturer's patient information (patient information and instructions for use).1 2

• Importance of patients reporting to their clinician any adverse reactions or other issues occurring after administration of factor XIII A-subunit (recombinant).1

• Risk of hypersensitivity reactions; importance of informing patients of manifestations (e.g., urticaria, rash, chest tightness, wheezing, hypotension, anaphylaxis) that may occur during or after administration of factor XIII A-subunit (recombinant).1

• Importance of informing patients of signs and symptoms of thrombosis (e.g., swelling and/or pain of limb or abdomen; chest pain; shortness of breath; loss of sensation or motor power; alteration in consciousness, vision, or speech).1

• Importance of advising patients that bleeding occurring during factor XIII A-subunit (recombinant) prophylaxis may be a sign of neutralizing antibody (inhibitor) formation.1

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Bloody nose
• bruise
• collection of blood under the skin
• deep, dark purple bruise
• fever
• itching, pain, redness, or swelling

• Chest pain
• cough
• dizziness or fainting
• hives
• pain in the chest, groin, or legs, especially the calves
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red, scaly, swollen, or peeling areas of the skin
• severe, sudden headache
• shortness of breath
• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty with moving
• general feeling of discomfort or illness
• headache
• joint pain
• muscle aches and pains

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to prevent bleeding in patients without Factor XIII A-subunit.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to Factor XIII or any other part of Tretten (factor XIII A-subunit (recombinant)).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are getting Factor VIIa.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Tretten with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Tretten is given as an injection into your vein (intravenous injection). These injections are given once a month. Your dose will depend on your body weight. Use the dose that your healthcare provider has prescribed for you based on your weight. Before injecting Tretten, it must be dissolved (reconstituted) using the sterile water that is provided in the package. Throw away any Tretten left in the vial after you inject your dose because it may become unsterile.