fibrinogen/thrombin (Rx)

Adverse effects reported were similar to use of gelatin sponge alone

>10%

Procedural pain (52%)

Nausea (26%)

Constipation (16%)

Incision site pain (12%)

1-10%

Pyrexia (8%)

Anemia (7%)

Vomiting (7%)

Hypotension (7%)

Pruritus (6%)

Hypertension (5%)

Antithrombin antibodies (2%)

Contraindications

Intravascular application

Severe or brisk arterial bleeding

Known anaphylactic or severe systemic reactions to human blood products

Cautions

Life-threatening thromboembolic events may result from intravascular application (see Contraindications)

Air or gas embolism has occurred with the use of spray devices using pressure regulators to administer fibrin sealants; this appears to be related to the use of the spray device at higher than manufacturer recommended pressures and in close proximity to the tissue surface; minimize this risk by precisely following manufacturer’s instructions for RaplixaSpray device (see Administration and product prescribing information)

Made from human plasma; risk of transmitting infectious agents (eg, CJD); manufacturing steps designed to reduce this risk are used, as is screening of plasma donors

Hypersensitivity reactions may occur, including hives, generalized urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis; if these symptoms occur, discontinue immediately

Pregnancy

Animal reproduction studies have not been conducted

It is also not known whether fibrinogen/thrombin can cause fetal harm when administered to pregnant women or can affect reproductive capacity

Should be given to a pregnant woman only if clearly needed

Lactation

Unknown if distributed in human breast milk; because many drugs are excreted in human milk, caution should be exercised when administering to breastfeeding women

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Mixture of human plasma-derived fibrinogen and human plasma-derived thrombin powders that are designed to mimic the final steps in the coagulation cascade

Powder dissolves readily on contact with aqueous fluids (eg, blood), activating thrombin, which triggers an immediate conversion of fibrinogen into fibrin and subsequent clot formation

Pharmacokinetics

Because fibrinogen/thrombin is applied only topically, systemic exposure or distribution to other organs or tissues is not expected

General Application

Apply to the surface of bleeding tissue only; administer directly from the vial or using the RaplixaSpray device

For topical use only

Do not reconstitute

Use within 1 hr of opening vial

May be used at multiple bleeding sites in the same patient

Use no more than 2 vials with the RaplixaSpray device

To administer a third vial, open a new device

Application with Gelatin Sponge

1. Open the pouch and take out the vial following standard sterile technique to ensure the vial and surgical field remain sterile

2. Check that the powder is in the bottom of the vial; remove the flip-off top, leaving the stopper in place until immediately prior to use

3. Prepare sterile gelatin sponge by trimming to an appropriate size for the bleeding site

4. Remove stopper and sprinkle a uniform thin coating of powder gently onto bleeding site and apply gentle pressure with gelatin sponge using sterile gauze, OR

Remove stopper and sprinkle a thin layer of powder gently onto a prewetted gelatin sponge and place onto the bleeding site with gentle pressure using sterile gauze

Application Using RaplixaSpray Device

1. Prepare the pressure regulator (air or CO2) according to the manufacturer’s instructions for use

2. Open the pouch and take out the vial following standard sterile technique to ensure the vial and surgical field remain sterile

3. Check that the powder is in the bottom of the vial; remove the flip-off top, leaving the stopper in place until use

4. Prepare gelatin sponge by trimming to an appropriate size for the bleeding site

5. To attach the vial to the RaplixaSpray device, invert the device and place the upright vial into the gray rubber ring on the device, turn the device upright, and return the device to the sterile field until use

6. Activate air or gas flow

7. Device is now ready for use; DO NOT push button until ready for use

8. Check that the pressure is 1.5 bar (22 psi)

9. Ensure the vial is kept within 45° of vertical at all times

10. Hold nozzle at a minimum distance of 5 cm (or 2 inches) from the bleeding site

11. Start application by gently pressing the operating button

12. Powder should cover the bleeding surface as a uniform thin coating; apply powder within 10-60 seconds

13. Immediately after powder application, place a gelatin sponge, trimmed to the approximate size, on top of the powder; the gelatin sponge may be used dry or moistened with sterile saline; a moistened sponge molds more easily to irregularly shaped and contoured bleeding areas; hold the gelatin sponge in place with manual pressure using sterile gauze

14. Hold the device upside down and carefully remove the empty vial; if needed, attach the second vial (repeat steps 1-14); use no more than 2 vials with the RaplixaSpray device

15. To administer a third vial, open a new RaplixaSpray delivery device (repeat steps 1-13)

Storage

Store unopened vials at 2-25°C (36-77°F); refrigeration is not required

Do not freeze

Do not use beyond the expiration date printed on the carton or vial

Use powder within 1 hr after opening a vial