Catridecacog - Dosage, Indication, Contraindication, and Administration

Overview

Catridecacog, also known as Factor XIII A-Subunit (Recombinant), is a recombinant form of the Factor XIII-A2 homodimer composed of two factors XIII (FXIII) A-subunits label. Exogenous replacement of this key coagulation factor is needed in managing and preventing bleeding episodes in people with a mutation of Factor XIII or congenital deficiency, a rare bleeding disorder.

How Does Catridecacog Work?

Factor XIII, also known as fibrin stabilizing factor (FSF), is an endogenous coagulation factor and the final enzyme in the blood coagulation cascade. Factor XIII circulates in the body as a heterotetramer composed of two catalytic A-subunits and two non-catalytic B-subunits (FXIII-A2B2). The factor XIII A2B2 pro-enzyme is cleaved when activated by thrombin at the site of injury, resulting in activation of the catalytic A-subunit and dissociation from its carrier B-subunit.

As a result, the active transglutaminase from subunit A crosslinks fibrin and other proteins, increasing the fibrin clot's mechanical strength and resistance to fibrinolysis. This contributes to increased platelet and clot adhesion to injured tissue, which improves blood coagulation and hemostasis maintenance.

Uses:

This medication is recommended for routine bleeding prevention in patients with congenital Factor XIII A-subunit deficiency. Using a validated assay, 35 IU/kg IV once monthly to achieve a trough level of FXIII activity of 10 percent. The dose may be adjusted if the recommended dose (35 IU/kg/month) does not produce satisfactory results.

Dosage:

Routine prophylaxis for bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency is 35 international units (IU) per kilogram body weight once monthly to achieve a target trough level of FXIII activity of 10 percent or higher using a validated assay. Consider adjusting the dose if the recommended 35 IU/kg dose does not provide adequate coverage.

Warnings:

Catridecacog should not be used in patients who have a hypersensitivity to the active ingredient or any of the excipients. Because increased levels of rFXIII increase the risk of thrombosis, health professionals should exercise caution in patients predisposed to thrombotic conditions. Improper storage of the product after reconstitution may result in sterility loss and increased levels of activated rFXIII.

For Patients

How to Prevent Bleeding?

Bleeding can occur as a result of injuries or certain medical conditions. Although this can cause anxiety and fear, bleeding has a healing purpose. Still, one should know how to treat common bleeding incidents like cuts and bloody noses and when to seek medical attention.

First aid do's to prevent bleeding:

• Assist the individual in remaining calm. Allow them to lie down if the cut is large or bleeding heavily. Raise the limb above the heart if the wound is on an arm or leg to slow the bleeding.

• Clear any visible debris from the wound.

• If the cut is minor, clean it with soap and water.

• After putting on clean latex gloves, apply firm pressure to the wound for about ten minutes with a folded cloth or bandage.

• If blood seeps through, add another cloth or bandage and apply pressure to the cut for another ten minutes.

• When the bleeding has stopped, cover the wound with a clean bandage.

Learn More About Catridecacog

When and How Often to Take Catridecacog?

Factor XIII is a protein that aids in blood clotting. The A-subunit, a component of factor XIII, strengthens the clot and prevents further bleeding. Patients with congenital factor XIII A-subunit deficiency lack the A-subunit, or it does not function properly, making them prone to excessive bleeding. Catridecacog, the active substance, has the same chemical structure as the human factor XIII A-subunit. Therefore, Catridecacog prevents bleeding in these patients by providing the factor XIII A-subunit.

How Effective Is Catridecacog?

Data from a long-term study in which patients were given Catridecacog to prevent bleeding supported the safety and effectiveness of Catridecacog in six children under six. There were no instances of bleeding in children who were given Catridecacog.

Things to Inform The Doctor Before They Prescribe Catridecacog to a Person:

Inform the doctor about the medical conditions, including:

• Pregnancy, suspecting about being pregnant or intending to become pregnant. It is unknown whether Catridecacog can harm the mother or the unborn child.

• Catridecacog is not known whether it is safe and effective during labor and delivery.

• Catridecacog may pass into the breast milk if the patient is breastfeeding.

• A blood clot history.

• Inform the healthcare provider about all medications, including prescription and non-prescription medications such as over-the-counter medications, supplements, or herbal remedies.

Starting Catridecacog

The actual international unit (IU) amount stated on each carton and vial is 2000 to 3125 IU/vial (667 to 1042 IU/mL after reconstitution).

How to Take Catridecacog?

Catridecacog is administered via vein injection (intravenous injection). These injections are administered once a month. The person's body weight will determine the dose. Use the dose prescribed by the healthcare provider based on the person's weight. Catridecacog must be dissolved (reconstituted) in the sterile water provided in the package before injection. After injecting the dose, discard any Catridecacog that remains in the vial because it may become unsterile.

Things to Do After Starting Catridecacog:

After starting Catridecacog, regularly schedule appointments with the doctor to conduct a physical and diagnostic test to detect abnormalities; based on the test results, the doctor will recommend dose continuation, reduction, elevation, or drug interruption.

Look Out for Side Effects:

Headache, injection site pain, pain in the extremities, and increased fibrin D dimer levels were the most common adverse reactions reported in clinical trials.

Dietary Alterations:

Give the doctor a list of all the medications, herbs, non-prescription drugs, and dietary supplements a person takes. Then, inform them about smoking, consuming alcohol, or using illegal drugs to interact with the medications.

What Should Be Done When a Person Misses a Dose?

In case of a missed dose, take it as soon as the person remembers it. If the next dose is approaching, skip the missed dose and resume the dosing schedule. Do not use an extra dose to compensate for a missed dose. If a person frequently forgets to take their medication, consider setting the alarm or asking a family member for a reminder. If one has missed too many doses recently, please consult the doctor to discuss changes to the dosing schedule or a new schedule to make up for missed doses.

What Should Be Done to Treat Catridecacog Overdose?

Do not exceed the recommended dose. Taking more medication will not alleviate the symptoms; instead, it may result in poisoning or serious side effects.

How to Store and Handle Catridecacog?

Before reconstitution, refrigerate at 2C - 8C (36F - 46F). Catridecacog remains stable until the expiration date is printed on the carton and vial label. Do not become paralyzed. Keep away from direct sunlight. Catridecacog should be used within three hours of being reconstituted. If the reconstituted product is not used immediately, keep it refrigerated or at room temperature no higher than 25°C (77°F) for up to three hours after reconstitution.

How to Dispose of Catridecacog?

After injection, dispose of the syringe, the vial with the vial adapter, any unused Catridecacog, and any other waste materials in accordance with the healthcare provider's instructions. After injection, properly dispose of the syringe, the vial with the vial adapter, any unused Catridecacog, and any other waste materials as directed by the healthcare provider.

Avoid Self-Medication:

• Take the drug as directed by the physician.

• Do not miss a dose or overdose to compensate for a missed dose. Inform the physician immediately.

• Also, schedule regular appointments with the physician to monitor the disease progression and recommend dose alteration.

For Doctors

Indication:

• Catridecacog coagulation factor XIII A-Subunit (Recombinant) prevents bleeding in patients with congenital factor XIII A-subunit deficiency.

• Catridecacog should not be used in patients who have a congenital factor XIII B-subunit deficiency.

Pharmacology

Mechanism of Action:

The final enzyme in the blood coagulation cascade is FXIII. When activated by thrombin at the site of vessel wall injury, FXIII helps to maintain hemostasis by crosslinking fibrin and other proteins in the fibrin clot. FXIII circulates in plasma as a heterotetramer (A2B2) made up of two FXIII A-subunits and two FXIII B-subunits held together by strong non-covalent interactions. The catalytic subunit is FXIII A, and the FXIII B-subunit acts as a carrier molecule for the FXIII A-subunit in circulation and is abundant in plasma.

The half-life of the FXIII A-subunit (A2) is extended when it is bound to the FXIII B-subunit (A2B2). FXIII is a pro-enzyme (pro-transglutaminase) that is activated in the presence of Ca 2+ by thrombin. The FXIII A-subunit is in charge of the enzymatic activity. When activated, the FXIII A-subunit dissociates from the FXIII B-subunit, exposing the FXIII A-active subunit's site. The active transglutaminase crosslinks fibrin and other proteins, increasing the mechanical strength and resistance to fibrinolysis of the fibrin clot and helping to improve platelet and clot adhesion to injured tissue. Coagulation factor XIII A-subunit is a pro transglutaminase (rFXIII (rA2) homodimer) that binds to free human FXIII B-subunit to form the heterotetramer (rA2B2) with a half-life similar to (A2B2). Thrombin has been shown to activate rFXIII in the presence of Ca2+. Activated rFXIII has been shown to increase the mechanical strength of fibrin clots, slow fibrinolysis, and improve platelet adhesion to the site of injury dose-dependently.

Pharmacodynamics:

Coagulation Factor XIII A-subunit (Recombinant) has been shown to have the same pharmacodynamic properties in plasma as endogenous FXIII after combining with available plasma B-subunits. When performed correctly, a qualitative assay of clot solubility is widely used as an indicator of FXIII deficiency; the test is positive only when the FXIII activity in the sample is close to zero. However, standard coagulation tests show normal results because the quality of the clot is affected. Furthermore, there are currently no markers that can quantify FXIII's in vivo pharmacodynamics.

Ingredients:

• A-Subunit of Coagulation Factor XIII (Recombinant).
• Sodium Chloride.
• Sucrose.
• Polysorbate 20.
• L-Histidine.

Absorption:

Peak plasma concentration (adults): 0.71 IU/mL; 0.48 IU/mL (children). AUC: 128.3 IU•hour/mL (adults); 107.8 IU•hour/mL (children).

Distribution:

Radioactivity was distributed to blood and highly perfused tissues, crossing the blood test and blood-brain barriers at low levels. The distribution of the blood's cellular fraction was minimal. No tissues had tissue at two h or 72 hours post-dose: plasma exposure ratios greater than one.

Metabolism:

Since Catridecacog belongs to a therapeutic class known to be degraded into smaller peptides and individual amino acids, no metabolism studies were conducted.

Elimination:

Based on radioactivity levels following an IV dose of 125I-Catridecacog, the primary route of excretion was established as urine. To a lesser extent, the biliary route is also an excretory route.

Toxicity:

Headache, pain in the extremities, injection site pain, and increased fibrin D dimer levels were the most common adverse reactions reported in clinical trials, 1 percent. Because of its anti-clotting activity, this medication may cause thromboembolic complications.

Warning and Precaution:

• Hypersensitivity Reaction - Catridecacog may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, and hypotension) occur, discontinue immediately and institute appropriate treatment.

• Inhibitors - Catridecacog may induce inhibitory antibodies. Patients who have inhibitory antibodies may have an inadequate response to treatment. If expected plasma FXIII activity levels are not met, or if breakthrough bleeding occurs while on prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.

• Thromboembolic Risk - Thromboembolic complications are possible. Therefore, after administering Catridecacog, patients with conditions predisposing them to thrombosis should be monitored for signs and symptoms.

Dosage and Forms:

Catridecacog, coagulation factor XIII A-Subunit (Recombinant), is a white lyophilized powder in single-use vials containing 2500 IU (2000-3125 IU) of recombinant coagulation factor XIII A-subunit. Each carton and vial clearly state the amount of Catridecacog in IU. Each vial contains 667 to 1042 IU/mL recombinant coagulation factor XIII A-subunit after reconstitution with the provided sterile water for injection.

Administration of the Drug:

• An aseptic technique should be used. Before injecting, wash your hands.

• Catridecacog (white lyophilized powder) and sterile injection water (diluent) should be brought to room temperature but not above 25°C (77°F).

• Take the plastic caps off the two vials.

• Before using the vials, clean the rubber stoppers with sterile alcohol swabs and allow them to dry.

• Remove the protective paper from the vial adapter, but leave the protective cap in place. Next, attach the vial adapter to the diluent vial without removing it from the protective cap. Once attached, gently squeeze the protective cap with the thumb and index finger to release it from the vial adapter.

• Draw back the plunger of the sterile syringe to allow 3.2 mL of air into the syringe.

• Screw the syringe onto the diluent vial's vial adapter.

• Inject the syringe's air into the diluent vial until resistance is felt. Then, with the diluent vial upside down, withdraw 3.2 mL of water into the syringe.

• Tip the syringe with the attached vial adapter to remove the empty diluent vial.

• Connect the syringe to the powder vial using the vial adapter. Keep the syringe slightly tilted with the vial facing down. Slowly push the plunger to inject all the water (3.2 mL) into the powder vial.

• Do not inject the diluent directly onto the Catridecacog powder to avoid foaming.

• Gently swirl the vial until all of the material has been dissolved. The vial should not be shaken. Catridecacog reconstituted is a clear, colorless solution.

• Use the reconstituted Catridecacog right away. If not, store the solution refrigerated or at room temperature for up to three hours at a temperature not exceeding 25°C (77°F). After three hours, discard.

Considerations for Administration:

Treatment should begin under the supervision of a physician who has experience treating rare bleeding disorders. Routine prophylaxis for bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency is 35 international units (IU) per kilogram body weight once monthly to achieve a target trough level of FXIII activity of 10 percent or higher using a validated assay. Before administration, visually inspect the reconstituted Catridecacog for particulate matter and discoloration. If particulate matter or discoloration is detected, do not use it. Administer at a rate of no more than 1 to 2 mL per minute. Do not combine with any other infusion solutions. Do not give it as a drip.

Contraindications:

Catridecacog is not recommended for patients with hypersensitivity to the active ingredient or excipients.

Clinical Studies for Catridecacog:

A multi-center, open-label, non-controlled trial was conducted for 52 weeks in 41 subjects to determine the efficacy of Catridecacog for preventing bleeding in patients with congenital FXIII A-subunit deficiency. Catridecacog at 35 IU/kg was given to all subjects every month. To assess the efficacy of monthly replacement therapy with Catridecacog in preventing bleeding episodes, bleeding episodes that required treatment with an FXIII-containing product were observed. Genotyping confirmed congenital FXIII A-subunit deficiency in the subjects.

Subjects who had previously received regular replacement therapy were required to have started it at least six months before screening and to have a documented history of at least one treatment-requiring bleeding episode before starting regular replacement therapy or a documented family history of FXIII congenital deficiency. Subjects who had only received on-demand treatment before entering the trial were required to have a documented history of at least two treatment-requiring bleeding episodes within 12 months of the screening visit.

Drug Interactions:

A single-dose study in monkeys looked at the possibility of drug interactions between Catridecacog and rFVIIa. There was no effect on exposure or other PK parameters.

Other Specifications:-

Catridecacogin Pregnant Women:

Pregnancy type C Catridecacog has not been used in animal reproduction studies. It is also unknown whether Catridecacog can cause fetal harm or affect reproduction capacity when administered to a pregnant woman. Therefore, Catridecacog should only be given to a pregnant woman if necessary.

Catridecacogin Lactating Women:

Catridecacog is not known to be excreted in human milk. However, because many drugs are excreted in human milk, Catridecacog should be cautiously administered to a nursing woman.

Catridecacogin Pediatric Patients:

Pediatric patients in phase 3 and extension studies included six children aged 0 to 5, 12 children aged 6 to 12, and 9 adolescents aged 13 to 17 who were treated with Catridecacog for a total of 652 exposures. Adverse reactions were reported more frequently in patients aged 6 to less than 18 years old than in adults; a greater number of possible trial drug-related events were reported in patients under 18 than in those over 18.

Catridecacogin Geriatric Patients:

Catridecacog's safety and efficacy in the geriatric population have yet to be established due to a lack of patients.