- INDICATIONS AND USAGE
Recobin X®, Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age.
Recobin X may be used in conjunction with an absorbable gelatin sponge, USP.
2. DOSAGE AND ADMINISTRATION
For topical use only. DO NOT INJECT.
2.1 Reconstitution of Recobin X
The volume of reconstituted Recobin X required will vary depending on the size and number of bleeding sites to be treated and the method of application.
Inspect the integrity of the Recobin X package and contents. Do not use if the packaging or contents have been damaged or opened.
Reconstitute the lyophilized powder using the supplied diluent.
Use aseptic technique when handling vials and syringes.
5000-unit Recobin X Reconstitution Units used herein represent international units of potency determined using a reference standard that has been calibrated against the World Health Organization Second International Standard for Thrombin.
1. Remove flip-off cap from the top of the Recobin X vial.
2. Attach the needle-free transfer device and snap it into place on the vial by placing the vial on
a flat surface and attaching the transfer device straight into the center of the vial stopper.
3.Attach the prefilled diluent syringe to the needle-free transfer device.
4. Inject the 5 mL of diluent from the syringe into the product vial. Keep the syringe plunger depressed.
5. DO NOT reuse the diluent syringe for transfer of the reconstituted product. Remove and discard the diluent syringe.
6. Gently swirl and invert the product vial until the powder is completely dissolved. Avoid excessive agitation. The powder should dissolve in less than one minute at room temperature.
7. Apply the pre-printed “DO NOT INJECT” label to the sterile, empty transfer syringe provided, then draw up the Recobin X solution. 20,000-unit Recobin X Reconstitution
1. Remove the flip-off cap from the top of the Recobin X vial and the diluent vial.
2. Attach a needle-free transfer device (one each) to the Recobin X and diluent vials and snap them into place by placing the vial on a flat surface and attaching the transfer device straight into the center of the vial stopper.
3. Open the sterile, empty 20-mL syringe package and apply the pre-printed “DO NOT INJECT” label to the syringe.
4. Attach the labeled 20-mL syringe to the needle-free transfer device on the diluent vial (injection of air into the diluent vial may facilitate withdrawal of the diluent).
5. Draw up 20 mL of diluent from the vial into the syringe.
6. Remove the diluent-filled syringe from the diluent vial and attach it to the transfer device on the Recobin X vial.
7. Transfer the 20 mL of diluent from the syringe into the Recobin X vial; the vacuum in the vial facilitates transfer.
8. Leave the syringe attached and gently swirl and invert the Recobin X vial until the powder is completely dissolved. Avoid excessive agitation. The powder should dissolve in less than one minute at room temperature.
9. With the same syringe, draw up the Recobin X solution.
2.2 Application Techniques
Topically apply Recobin X solution directly or in conjunction with absorbable gelatin sponge onto the bleeding site. DO NOT INJECT.
The amount required depends upon the area of tissue to be treated and the method of application. Vials are for single use only. Discard unused contents. Use with Absorbable Gelatin Sponge Refer to the absorbable gelatin sponge labeling for safety information and instructions on appropriate use.
1. Transfer solution from syringe to a sterile bowl or basin.
2. Place the desired size pieces of the absorbable gelatin sponge into the bowl containing reconstituted Recobin X to completely saturate the sponge(s).
3. Remove the saturated sponge(s) and squeeze gently to remove excess Recobin X.
4. Apply the sponge to the bleeding site in a single layer. Use with ZymoGenetics Spray Applicator Kit
1. Hold the outer sealed tray, peel back the lid, and aseptically transfer the inner sealed sterile tray to the sterile field.
2. Open the inner tray seal and use the sterile bowl as the receptacle for reconstituted Recobin X solution.
3. Refer to Spray Applicator Kit instructions for spray pump and syringe spray assembly and use.
3 DOSAGE FORMS AND STRENGTHS
Recobin X is available as a sterile lyophilized powder in 5000- and 20,000-unit single-use vials. When reconstituted with the sterile 0.9% sodium chloride, USP provided, the powder yields a solution containing 1000 units/mL of Thrombin topical (Recombinant).
4 CONTRAINDICATIONS
• Do not inject directly into the circulatory system.
• Do not use for the treatment of massive or brisk arterial bleeding.
• Do not administer to patients with a history of hypersensitivity to Recobin X or any components of Recobin X.
• Do not use in patients with known hypersensitivity to hamster proteins.
5 WARNINGS AND PRECAUTIONS
5.1 Thrombosis
Recobin X may cause thrombosis if it enters the circulatory system. Apply topically. DO NOT INJECT.
5.2 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, may occur. Recobin X is produced in a genetically modified Chinese Hamster Ovary (CHO) cell line and may contain hamster or snake proteins [see Contraindications (4) and Description (11)].
6 ADVERSE REACTIONS
Thromboembolic adverse reactions were reported in 6% of surgical patients treated with Recobin X in all completed clinical trials (N=644) [see Warnings and Precautions (5.1)].
Antibody formation to Recobin X occurred in <1% of patients. None of the antibodies detected neutralized native human thrombin [see Adverse Reactions (6.2)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug product cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical trials have been performed with Recobin X applied with absorbable gelatin sponge and applied with a spray applicator. A total of 644 patients were exposed to Recobin X in these studies.
7 USE IN SPECIFIC POPULATIONS
7.1 Pregnancy
Pregnancy Category C
Animal reproduction studies have not been conducted with Recobin X. It is also not known whether Recobin X can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Recobin X should be given to a pregnant woman only if clearly needed.
7.2 Pediatric Use
A total of 30 pediatric patients, ages 0 to 16 years (one month to 2 years, n=10; 2 to 12 years, n=12; 12 to 16 years, n=8), were treated in clinical trials with Recobin X using a spray applicator to burn wound excision sites prior to autologous skin grafting. No patient experienced a thromboembolic adverse reaction. The safety of Recobin X in pediatric patients greater than or equal to one month of age is supported by these data and by extrapolation of efficacy from adequate and well-controlled studies of Recobin X in adults. Safety and efficacy have not been established in neonates [see Adverse Reactions (6)].
7.3 Geriatric Use
Of 644 patients in clinical studies of Recobin X, 36% (n=232/644) were ≥65 years old and 15% (n=95/644) were ≥75 years old.
No differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
8 DESCRIPTION
Recobin X, Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. Recobin X is 1 identical in amino acid sequence and structurally similar to naturally occurring human thrombin. Recobin X precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture Recobin X has been tested and
shown to be free of known infectious agents. The cell culture process used in the manufacture of Recobin X employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance.
Recobin X is provided as a sterile, white to off-white, preservative-free, lyophilized powder in vials for reconstitution with diluent (sterile 0.9% sodium chloride, USP). Reconstitution with the provided diluent, as described [see Dosage and Administration (2.1)], yields a solution with a pH of 6.0 containing 1000 units/mL of recombinant thrombin for topical use. The formulated product is a clear, colorless solution upon reconstitution and contains the following excipients:
histidine, mannitol, sucrose, polyethylene glycol 3350, sodium chloride, and calcium chloride dihydrate, USP.