Thrombin Alfa (Recombinant) (Topical) (Monograph)

Brand name: Recothrom
Drug class: Hemostatics
VA class: BL116
Chemical name: Human thrombin (recombinant, glycosylated)
Molecular formula: C₁₅₁₁H₂₃₄₂N₄₁₈O₄₃₆S₁₅
CAS number: 869858-13-9

Introduction

Hemostatic agent; biosynthetic (recombinant DNA origin) preparation of naturally occurring human thrombin.

Uses for Thrombin Alfa (Recombinant) (Topical)

Hemorrhage

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.

May be used alone or in conjunction with an absorbable gelatin sponge during various types of surgery (e.g., spinal surgery, liver resection, peripheral arterial bypass surgery).

Do not use for massive or brisk arterial bleeding. (See Contraindications.)

Thrombin Alfa (Recombinant) (Topical) Dosage and Administration

Administration

Topical Administration

Apply topically as a solution; do not inject. (See Contraindications.) Separate topical thrombin solutions from parenteral preparations to avoid inadvertent injection. (See Thrombosis under Cautions.) Do not leave reconstituted solutions in syringes as an intermediate step.

Apply directly to surfaces of bleeding tissue using a sterile syringe sprayer or spray pump; alternatively, may apply with an absorbable gelatin sponge. Consult manufacturer's instructions for proper assembly and use of the syringe sprayer or spray pump (available as part of the spray applicator kit).

When used in conjunction with an absorbable gelatin sponge, transfer solution to a sterile bowl or basin. Immerse sponge strips of the desired size in solution to allow complete saturation. Gently squeeze sponge strips to remove excess drug and apply to bleeding site in a single layer. Consult manufacturer's information for detailed instructions on use of absorbable gelatin sponge preparations.

Reconstitution

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. Gently swirl vial until powder is completely dissolved.

Draw reconstituted solution into a sterile syringe and apply auxiliary label indicating that the solution is for topical use only.

Use within 24 hours of reconstitution.

Dosage

Adults

Hemorrhage

Topical

Volume of drug required to achieve hemostasis depends on total number of bleeding sites, surface area being treated, and method of application.

Hemostasis usually achieved within 10 minutes following a single application.

Cautions for Thrombin Alfa (Recombinant) (Topical)

Contraindications

• Do not inject directly into circulatory system. (See Thrombosis under Cautions.)

• Treatment of massive or brisk arterial bleeding.

• Known hypersensitivity to thrombin alfa, hamster proteins, or any ingredient in the formulation.

Warnings/Precautions

Warnings

Thrombosis

Risk of thrombosis if absorbed systemically. Do not inject directly into the circulatory system; serious complications including hypotension, systemic thrombosis, and death may result. (See Contraindications under Cautions.) Take appropriate precautionary measures to avoid inadvertent injection. (See Administration under Dosage and Administration.)

Sensitivity Reactions

Hypersensitivity

Potential allergic reaction in patients with known hypersensitivity to snake proteins (due to use of snake-venom-derived prothrombin activator in production process).

Antibody Formation

Possible development of antibodies to thrombin alfa; risk of antibody development lower than that associated with bovine-derived thrombin. Relationship between antibody formation and clinically important adverse effects (e.g., excessive bleeding) not observed.

Immunogenicity of thrombin alfa not affected by preexisting antibodies to bovine thrombin.

Limited experience with repeated exposure to the drug.

Specific Populations

Pregnancy

Category C.

Pediatric Use

Evaluated in a limited number of pediatric patients (12–17 years of age) undergoing burn wound excision prior to grafting. Manufacturer states safety and efficacy in pediatric patients <12 years of age not established.

Geriatric Use

No overall differences in efficacy or safety relative to younger patients, but increased sensitivity cannot be ruled out.

Common Adverse Effects

Incision site complications.

Thrombin Alfa (Recombinant) (Topical) Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed (<0.37%) following topical application to the liver in a rabbit wound model.

Onset

Time to hemostasis dependent on concentrations of thrombin and fibrinogen present during clot formation.

Elimination

Elimination Route

Rapidly (< 5 minutes) neutralized by endogenous inhibitors in circulation; cleared by liver.

Stability

Storage

Topical

Powder

2–25°C.

May store reconstituted solution at 2–25°C for up to 24 hours; discard after 24 hours.

Actions

• 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.

• Converts fibrinogen directly to fibrin at site of vessel injury without the addition of other substances.

• Rapidly inactivated by endogenous inhibitors (e.g., antithrombin III human, heparin cofactor II, α₂-macroglobulin) to prevent systemic coagulation.

• 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.

• Structurally and functionally similar to endogenous human thrombin.

Advice to Patients

Risk of blood clotting disorders if absorbed systemically; importance of contacting a clinician if any new or unusual symptoms of thrombosis occur.

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

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

Importance of informing patients of other important precautionary information. (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.

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