Thrombin (Topical)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Pad, topical [preservative free; bovine derived]:

Thrombi-Pad 3x3: ≥200 units (10s)

Powder for reconstitution, topical [bovine derived]:

Thrombin-JMI: 5000 units, 20,000 units [supplied with diluent]

Thrombin-JMI Epistaxis kit: 5000 units [supplied with diluent]

Thrombin-JMI Pump Spray Kit: 20,000 units [supplied with diluents]

Thrombin-JMI Syringe Spray Kit: 5000 units; 20,000 units [supplied with diluent]

Powder for reconstitution, topical [preservative free; recombinant]:

Recothrom: 5000 units; 20,000 units [production involves products derived from hamster and snake sources; supplied with diluent]

Recothrom Spray Kit: 20,000 units [production involves products derived from hamster and snake sources; supplied with diluent]

Solution, topical [human derived]:

Evithrom: 800-1200 units/mL (2 mL [DSC], 5 mL [DSC], 20 mL[DSC])

Sponge, topical [preservative free; bovine derived]:

Thrombi-Gel 10: ≥1000 units (10s)

Thrombi-Gel 40: ≥1000 units (5s)

Thrombi-Gel 100: ≥2000 units (5s)

Pharmacology

Mechanism of Action

Activates platelets and catalyzes the conversion of fibrinogen to fibrin to promote hemostasis.

Use: Labeled Indications

Hemostasis aid:

Evithrom, Recothrom, Thrombin-JMI only: As an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical.

Thrombi-Gel, Thrombi-Pad only: As a trauma dressing for temporary control of moderate to severe bleeding wounds; control of surface bleeding from vascular access sites and percutaneous catheters and tubes.

Contraindications

Known hypersensitivity to any component of the formulation.

Evithrom: Additional contraindications: Known anaphylactic or severe systemic reactions to blood products; treatment of severe or brisk arterial bleeding

Recothrom: Additional contraindications: Known hypersensitivity to hamster proteins; injection directly into the circulatory system; treatment of massive or brisk arterial bleeding.

Thrombi-Gel: Additional contraindications: Use in the closure of skin incisions.

Thrombin-JMI: Additional contraindications: Known sensitivity to material of bovine origin; injection directly into the circulatory system; re-exposure if there are known or suspected antibodies to bovine thrombin and/or factor V; treatment of severe or brisk arterial bleeding.

Thrombi-Pad: Additional contraindications: Known sensitivity to bovine-derived materials.

Dosage and Administration

Dosing: Adult

Hemostasis aid: Topical: Note: For topical use only; do not administer intravenously or intra-arterially:

Evithrom: Dose depends on area to be treated; for direct application, flood treatment area; up to 10 mL was used with absorbable gelatin sponge in clinical studies.

Recothrom: Dose depends on area to be treated. Apply to the bleeding site directly or in conjunction with absorbable gelatin sponge.

Thrombi-Gel: Apply directly over source of the bleeding with adjunct manual pressure until hemostasis is achieved.

Thrombin-JMI:

Solution: Apply 1,000 to 2,000 units/mL of solution where bleeding is profuse. Apply 100 units/mL for bleeding from skin or mucosal surfaces (eg, skin grafting, dental extractions, plastic surgery).

Powder: May apply dry powder directly to the site on oozing surfaces.

Thrombi-Pad: Apply dry or wetted pad directly over source of bleeding with adjunct manual pressure. If desired, product may be left in place for up to 24 hours; do not leave in the body.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemostasis: Topical: Note: For topical use only; do not administer intravenously or intra-arterially:

Evithrom: Infants, Children, and Adolescents: Dose depends on area to be treated; may apply directly or in conjunction with an absorbable gelatin sponge; up to 10 mL was used with absorbable gelatin sponge in clinical studies

Recothrom: Infants ≥1 month, Children, and Adolescents: Dose depends on area to be treated including size of and number of bleeding sites; may apply directly or in conjunction with an absorbable gelatin sponge

Reconstitution

Evithrom: Reconstitute with 2 mL of SWFI using device provided by the manufacturer. Shake gently to dissolve until clear.

Recothrom: Reconstitute using diluent provided in prefilled syringe. Gently swirl to dissolve powder; avoid excessive agitation; powder should dissolve within 1 minute at room temperature. For some vial sizes, do not use diluent syringe to withdraw solution from vial.

Thrombi-Gel: Must wet with NS or SWFI before use; may cut or roll to desired shape prior to wetting. Refer to manufacturer’s labeling for fluid volume used for wetting a specific product. Once wetted and prior to applying, knead thoroughly to saturate the pad and remove trapped air bubbles.

Thrombin-JMI: Used as drug powder or wetted. If wetted, reconstitute with NS or provided diluent to a concentration of 1,000 to 2,000 units/mL using a syringe or transfer device. In cases in which approximately 1,000 units/mL is desired, reconstitute with entire vial of provided diluent. When used with Gel-Flow NT, reconstitute the 5,000 unit syringe spray kit with 5 mL NS.

Thrombi-Pad: Used dry or wetted with up to 10 mL of NS.

Administration

For topical use only; do not administer intravenously or intra-arterially.

Evithrom: Sponge or suction target surface free of blood prior to application (do not wipe). Use syringe and small-gauge needle to apply; avoid sponging the clot after application. When used in conjunction with absorbable gelatin sponge, transfer solution to sterile container and immerse gelatin sponge(s) into solution; vigorously knead until all air is expelled and sponge can return to its original size and shape; hold sponge in place with gauze or cotton pledget using moderate pressure until hemostasis is achieved.

Recothrom: May apply reconstituted solution directly using ZymoGenetics spray applicator kit or in combination with absorbable gelatin sponge. When using spray applicator, use the sterile bowl in kit as receptacle for reconstituted solution; refer to spray kit manufacturer’s labeling for spray pump and syringe spray assembly and use. When used in conjunction with absorbable gelatin sponge(s), transfer solution to sterile container and immerse gelatin sponge(s) into solution until completely saturated; gently squeeze to remove excess solution; apply sponge(s) to bleeding site in a single layer.

Thrombi-Gel: After wetting, place directly over bleeding source and apply adjunct manual compression until hemostasis is achieved; may cut or roll to desired shape prior to wetting.

Thrombin-JMI: Sponge (do not wipe) application surface prior to use, if possible. Apply as dry powder or reconstituted solution. When used as a solution, flood surface using a sterile syringe with a small-gauge needle or use in conjunction with Thrombin-JMI pump spray kit, syringe spray kit, or epistaxis kit; refer to manufacturer’s kit labeling for assembly and use. The 5,000 unit syringe spray kit may be used to saturate gelatin powder in Gel-Flow NT; mixture may be smeared, filled or pressed against surface to control bleeding (refer to Gel-Flow NT product labeling for preparation instructions). When used in conjunction with absorbable gelatin sponge, immerse sponge strips into solution; vigorously knead sponge with moistened gloved fingers until all air is expelled; apply saturated sponge to bleeding area; hold in place with gauze or cotton pledget using moderate pressure until hemostasis is achieved. Product is most effective when it mixes freely with blood as soon as it reaches the surface. Avoid sponging of treated surfaces.

Thrombi-Pad: Apply dry or wet directly to the bleeding source and apply adjunct manual compression; may be left in place for up to 24 hours. To remove, do not disrupt clot by physical manipulation. If pad adheres to the site, irrigate with nonheparinized NS and remove.

Storage

All products: Store at 2°C to 25°C (36°F to 77°F) prior to reconstitution or wetting.

Evithrom: Protect from light. Following reconstitution, may store at 2°C to 25°C (36°F to 77°F) for up to 8 hours. Do not freeze or refrigerate reconstituted solution.

Recothrom: Do not freeze. Following reconstitution, may store at 2°C to 25°C (36°F to 77°F) for up to 24 hours.

Thrombi-Gel: After wetting, use within 3 hours.

Thrombin-JMI: Solutions may be stored at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature for up to 8 hours after reconstitution.

Thrombi-Pad: If pad is wetted, use within 1 hour.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not always defined.

Cardiovascular: Thromboembolism (1% to 9%)

Dermatologic: Pruritus

Gastrointestinal: Nausea, vomiting

Hematologic & oncologic: Increased INR, increased neutrophils, lymphocytopenia, prolonged partial thromboplastin time, prolonged prothrombin time

Hypersensitivity: Hypersensitivity reaction

Immunologic: Antibody development (≤2%)

Local: Postoperative wound complication

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, may occur. Institute supportive measure and treat individual symptoms immediately.

Dosage form specific issues:

• Human plasma product: Evithrom is a product of human plasma; may potentially contain infectious agents that could transmit infectious agents, such as viruses and, theoretically the Creutzfeldt-Jacob disease agent, or unknown infectious agents. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
• Infection risk: Thrombi-Gel and Thrombi-Pad: Do not use in the presence of infection; use caution in areas of contamination.
• Nonabsorbable product: Thrombi-Pad: Do not use as a replacement for absorbable hemostats. Product is nonabsorbable; do not leave in the body.
• Proteins (snake and hamster origin): Recothrom: Use caution in patients with known hypersensitivity to snake or hamster proteins (manufacturing process uses a genetically modified hamster cell line and snake proteins); the potential for allergic reaction theoretically exists.
• Severe bleeding and thrombosis complications: Thrombin-JMI, Thrombi-Gel, and Thrombi-Pad only. [US Boxed Warning]: Thrombin topical (bovine) can cause fatal severe bleeding or thrombosis. Thrombosis may result from the development of antibodies against bovine thrombin. Bleeding may result from the development of antibodies against factor V. These may cross-react with human factor V and lead to its deficiency. Do not re-expose patients to thrombin topical (bovine) if there are known or suspected antibodies to bovine thrombin and/or factor V. Monitor patients for abnormal coagulation laboratory values, bleeding, or thrombosis.

Other warnings/precautions:

• Administration: For topical use only. Do not inject intravenously or intra-arterially. Intravascular clotting, possibly leading to death, may occur following injection. Powder and solution formulations may be used in combination with absorbable gelatin sponges; The 5,000 unit syringe spray kit may be used in conjunction with Gel-Flow NT.

Monitoring Parameters

Signs of hypersensitivity, bleeding, thrombosis, abnormal coagulation laboratory values.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Reproduction studies conducted with the solvent/detergent used in processing the human-derived product (Evithrom) showed adverse events in animals. Only residual levels of the solvent/detergent would be expected to remain in the finished product.

Patient Education

What is this drug used for?

• It is used to treat or prevent bleeding.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop
• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight
• DVT like swelling, warmth, numbness, change in color, or pain in the extremities
• Skin infection
• Chest pain
• Shortness of breath
• Loss of strength and energy
• Severe dizziness
• Passing out
• Fast heartbeat
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.