most efficient [1%:<18 years of age than in adults. 1 (See Immunogenicity under Cautions.) Pharmacokinetic parameters are similar across different age groups, including in pediatric patients. 1 Geriatric Use Safety and efficacy not established in geriatric patients. 1 Common Adverse Effects Headache, 6 7 extremity pain, 1 7 injection site pain, 1 increased fibrin D dimer levels. 1 Interactions for Factor XIII A-Subunit (Recombinant) Specific Drugs Drug Interaction Comments Factor VIIa (recombinant) Potential additive thrombotic effects and increased risk of thrombosis 1 Monitor closely for thrombosis 1 Factor XIII A-Subunit (Recombinant) Pharmacokinetics Absorption Duration After IV administration of 35 units/kg, plasma factor XIII activity increases to adequate levels and normal clot solubility is restored for approximately 28 30 days. 7 35 36 37 Plasma Concentrations After IV administration, plasma concentrations increase in dose-dependent manner. 7 Distribution Extent Remains principally within intravascular space. 7 35 Not known whether distributed into human milk. 1 Elimination Half-life Approximately 5 15 days. 1 35 36 37 Stability Storage Parenteral Powder for Injection 2 8°C; avoid freezing. 1 Protect from light. 1 Reconstituted solutions: May store in refrigerator or at room temperature ( 25°C) for up to 3 hours after reconstitution. 1 Actions Biosynthetic (recombinant DNA origin) preparation of human factor XIII A 2 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 (α 2 -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 (A 2 B 2 ). 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 A 2 B 2 . 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 Advice to Patients 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.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Factor XIII A-Subunit (Recombinant) Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV use only number of units indicated on label Tretten (with sterile water for injection diluent; available with vial adapter) Novo Nordisk AHFS DI Essentials. Copyright 2017, Selected Revisions February 27, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Novo Nordisk. Tretten Coagulation factor XIII A-subunit (recombinant) prescribing information. Plainsboro, NJ; 2014 April. 2. Novo Nordisk. Tretten Coagulation factor XIII A-subunit (recombinant) patient information. Plainsboro, NJ; 2014 April. 3. Novo Nordisk. Tretten Coagulation factor XIII A-subunit (recombinant) instructions for use. Plainsboro, NJ; 2014 April. 4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD. From FDA web site. 5. Food and Drug Administration. Summary Basis for Regulatory Action: STN BLA#125398/0. From FDA website. 6. Inbal A, Oldenburg J, Carcao M et al. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood . 2012; 119:5111-7. [PubMed 22451421] 7. Lovejoy AE, Reynolds TC, Visich JE. Safety and pharmacokinetics of recombinant factor XIII-A2 administration in patients with congenital factor XIII deficiency. Blood . 2006; 108:57-62. [Epub 2006 Mar 23.] [PubMed 16556896] 8. Karimi M, Bereczky Z, Cohan et al. Factor XIII deficiency. Semin Thromb Hemost . 2009; 35:426-38. [Epub 2009 Jul 13.] Review. [PubMed 19598071] 9. Bagoly Z, Koncz Z, Hársfalvi J et al. Factor XIII, clot structure, thrombosis. Thromb Res . 2012; 129(3):382-7. [Epub 2011 Dec 24]. [PubMed 22197181] 10. CSL Behring LLC. Corifact Factor XIII concentrate (human) prescribing information. Kankakee, IL; 2013 Jan. 11. Kohler HP. Novel treatment for congenital FXIII deficiency. Blood . 2012; 119:5060-1. [PubMed 22653950] 12. Visich JE, Zuckerman LA, Butine MD et al. Safety and pharmacokinetics of recombinant factor XIII in healthy volunteers: a randomized, placebo-controlled, double-blind, multi-dose study. Thromb Haemost . 2005; 94:802-7. [PubMed 16270634] 13. Odame JE, Chan AK, Wu JK et al. Factor XIII deficiency management: a review of the literature. Blood Coagul Fibrinolysis . 2014; 25:199-205. [PubMed 24401950] 30. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendation regarding the use of recombinant clotting factor products with respect to pathogen transmission (May 6, 2014). MASAC recommendation #226. From National Hemophilia Foundation website. 31. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders (revised April 2014). MASAC recommendation #225. From National Hemophilia Foundation website. 32. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations regarding factor concentrate prescriptions and formulary development and restrictions (March 12, 2005). MASAC recommendation #159. From National Hemophilia Foundation website. 34. Bolton-Maggs PH, Perry DJ, Chalmers EA et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia . 2004; 10:593-628. [PubMed 15357789] 35. Kerlin B, Brand B, Inbal A et al. Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A-subunit deficiency. J Thromb Haemost . 2014; 12:2038-43. [PubMed 25263390] 36. Brand-Staufer B, Carcao M, Kerlin BA et al. Pharmacokinetic characterization of recombinant factor XIII (FXIII)-A2 across age groups in patients with FXIII A-subunit congenital deficiency. Haemophilia . 2015; :. [PubMed 25643920] 37. Williams M, Will A, Stenmo C et al. Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. Haemophilia . 2014; 20:99-105. [PubMed 23834599] 38. Acharya SS. Rare bleeding disorders in children: identification and primary care management. Pediatrics . 2013; 132:882-92. [PubMed 24127475] 39. Novo Nordisk, Plainsboro, NJ: Personal communication. Next Interactions Print this page Add to My Med List More about factor XIII Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: miscellaneous coagulation modifiers Consumer resources Factor XIII ... +3 more Professional resources Factor XIII (Human) (AHFS Monograph) Factor XIII A-Subunit (Recombinant) (Wolters Kluwer) Factor XIII Concentrate (Human) (Wolters Kluwer) Other brands: Corifact , Tretten Related treatment guides Factor XIII Deficiency> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Drug Class Miscellaneous coagulation modifiers Related Drugs Factor XIII Deficiency factor XIII , More... Factor XIII Rating No Reviews - Be the first! No Reviews - Be the first! 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