Generic Name: Thrombin (Recombinant)
VA Class: BL116
Uses for Recothrom
Used topically as an aid in achieving hemostasis at accessible sites of oozing blood and minor bleeding from capillaries and small venules when control of bleeding using standard surgical measures (e.g., suture, ligature, electrocautery) is ineffective or impractical.1 2 4 6 11
Recothrom Dosage and Administration
Apply topically as a solution; do not inject.1 2 6 7 11 102 (See Contraindications.) Separate topical thrombin solutions from parenteral preparations to avoid inadvertent injection.102 (See Thrombosis under Cautions.) Do not leave reconstituted solutions in syringes as an intermediate step.102
Apply directly to surfaces of bleeding tissue using a sterile syringe sprayer or spray pump; alternatively, may apply with an absorbable gelatin sponge.1 6 12 Consult manufacturer's instructions for proper assembly and use of the syringe sprayer or spray pump (available as part of the spray applicator kit).1 12
When used in conjunction with an absorbable gelatin sponge, transfer solution to a sterile bowl or basin.1 6 Immerse sponge strips of the desired size in solution to allow complete saturation.1 6 Gently squeeze sponge strips to remove excess drug and apply to bleeding site in a single layer.1 6 Consult manufacturer's information for detailed instructions on use of absorbable gelatin sponge preparations.1
Using a needle-free transfer device, add 5 or 20 mL of the supplied diluent (0.9% sodium chloride injection) to a vial containing 5000 or 20,000 units, respectively, of lyophilized thrombin alfa (thrombin [recombinant]) to provide a solution containing 1000 units/mL.1 Gently swirl vial until powder is completely dissolved.1
Use within 24 hours of reconstitution.1
Cautions for Recothrom
Risk of thrombosis if absorbed systemically.1 6 11 Do not inject directly into the circulatory system; serious complications including hypotension, systemic thrombosis, and death may result.1 7 11 12 102 (See Contraindications under Cautions.) Take appropriate precautionary measures to avoid inadvertent injection.102 (See Administration under Dosage and Administration.)
Possible development of antibodies to thrombin alfa; risk of antibody development lower than that associated with bovine-derived thrombin.1 2 4 6 7 Relationship between antibody formation and clinically important adverse effects (e.g., excessive bleeding) not observed.1 2 3 6
Immunogenicity of thrombin alfa not affected by preexisting antibodies to bovine thrombin.14
Evaluated in a limited number of pediatric patients (12–17 years of age) undergoing burn wound excision prior to grafting.13 Manufacturer states safety and efficacy in pediatric patients <12 years of age not established.12 13
No overall differences in efficacy or safety relative to younger patients, but increased sensitivity cannot be ruled out.1
Common Adverse Effects
Incision site complications.1
Minimally absorbed (<0.37%) following topical application to the liver in a rabbit wound model.11
May store reconstituted solution at 2–25°C for up to 24 hours; discard after 24 hours.1
Promotes hemostasis principally by converting fibrinogen to fibrin; other mechanisms (e.g., platelet activation and aggregation, activation of factor XIII leading to fibrin crosslinking and clot stabilization) also involved.1 2 4 5 6 7 10 11
Prepared using recombinant DNA technology in a genetically modified mammalian cell (Chinese hamster ovary) expression system free of animal or human additives; undergoes additional purification steps (e.g., nanofiltration, solvent/detergent) to further reduce risk of viral transmission.1 2 3 5 11
Advice to Patients
Importance of women informing clinicians 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.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Recothrom (with 0.9% sodium chloride diluent; package also contains needle-free transfer device and 5-mL sterile syringe)
Recothrom (with 0.9% sodium chloride diluent; package also contains 2 sterile needle-free transfer devices and 20-mL sterile syringe)
Recothrom (with 0.9% sodium chloride diluent; spray applicator kit contains spray pump, spray bottle, syringe spray tip, syringe, and bowl)
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 31, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. ZymoGenetics, Inc. Recothrom (thrombin [recombinant]) powder for solution prescribing information. Seattle, WA; 2009 May.
2. Chapman WC, Singla N, Genyk Y et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007; 205:256-65. [PubMed 17660072]
3. Chapman WC, Lockstadt H, Singla N et al. Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical evaluation of recombinant human thrombin in multiple surgical indications. J Thromb Haemost. 2006; 4:2083-5. [PubMed 16961621]
4. Weaver FA, Lew W, Granke K et al. A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures. J Vasc Surg. 2008; 47:1266-73. [PubMed 18440754]
5. Bishop PD, Lewis KB, Schultz J et al. Comparison of recombinant human thrombin and plasma-derived human alpha-thrombin. Semin Thromb Hemost. 2006; 32 Suppl 1:86-97. [PubMed 16673270]
6. Cada DJ, Levien T, Baker DE. Thrombin, topical (recombinant). Hosp Pharm. 2008; 43:577-85.
7. Heffernan JK, Ponce RA, Zuckerman LA et al. Preclinical safety of recombinant human thrombin. Regul Toxicol Pharmacol. 2007; 47:48-58. [PubMed 16971028]
8. King Pharmaceuticals, Inc. Thrombin-JMI thrombin (bovine origin) prescribing information. Middleton, WI; 2007 Nov.
9. Johnson and Johnson Wound Management. Evithrom thrombin (human) for topical use prescribing information. Somerville, NJ; 2007 Sep.
10. Lundblad RL, Bradshaw RA, Gabriel D et al. A review of the therapeutic uses of thrombin. Thromb Haemost. 2004; 91:851-60. [PubMed 15116244]
11. Anderson CD, Bowman LJ, Chapman WC. Topical use of recombinant human thrombin for operative hemostasis. Expert Opin Biol Ther. 2009; 9:133-7. [PubMed 19063699]
12. Zymogenetics, Seattle, WA: Personal communication.
13. Greenhalgh DG, Gamelli RL, Collins J et al. Recombinant thrombin: Safety and immunogenicity in burn wound excision and grafting. J Burn Care Res. 2009; 30:1-9. [PubMed 19060769]
14. Singla NK, Ballard JL, Moneta G et al. A phase 3b, open-label, single-group immunogenicity and safety study of topical recombinant thrombin in surgical hemostasis. J Am Coll Surg. 2009; 209:68-74. [PubMed 19651065]
15. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007; 21:131-42. [PubMed 17208341]
102. Cohen MR, Smetzer JL. ISMP medical error report analysis: Danger of giving topical thrombin intravascularly. Hosp Pharm. 2007; 42:284-5.