Data from FDA - Curated by Toby Galbraith - Last updated 18 April 2017

Licensing authority

FDA (Food and Drug Administration, USA)

Indication(s)

1 INDICATIONS AND USAGE Raplixa is a fibrin sealant indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical.

Raplixa is used in conjunction with an absorbable gelatin sponge (USP) and may be applied directly or using the RaplixaSpray device.

Raplixa is a fibrin sealant indicated as an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical.

Raplixa is used in conjunction with an absorbable gelatin sponge (USP) and is applied directly or using the RaplixaSpray device.

(1)

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Advisory information

contraindications

4 CONTRAINDICATIONS Do not apply intravascularly.

Do not use for the treatment of severe or brisk arterial bleeding.

Do not use in patients known to have anaphylactic or severe systemic reactions to human blood products.

Do not use: Intravascularly.

For the treatment of severe or brisk arterial bleeding.

In patients known to have anaphylactic or severe systemic reactions to human blood products.

(4)

Adverse reactions

6 ADVERSE REACTIONS The most commonly reported adverse reactions (> 5 % subjects) were procedural pain, nausea, constipation, pyrexia, and hypotension.

The most commonly reported adverse reactions (> 5 % subjects) were procedural pain, nausea, constipation, pyrexia, and hypotension.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company Support center phone number: 1-888-977-6326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience The Raplixa clinical trials safety data base consists of two randomized, single-blind, controlled Phase 2 trials and one randomized single-blind controlled Phase 3 trial.

All of the trials evaluated the safety and immunogenicity of Raplixa topically applied with a gelatin sponge and included patients undergoing spinal surgery, vascular surgery, hepatic resection, soft tissue dissection/general surgery.

These trials resulted in an overall safety database of 566 patients treated with

Raplixa with gelatin sponge.

Most patients (94 %) were exposed to a 1 gram vial of Raplixa.

Overall, the incidence of adverse reactions was similar between treatment groups (Table 2).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Table 2: Commonly Reported Adverse Reactions (> 5 % subjects) in Raplixa Clinical Trials a FC-002 US and FC-002 NL clinical trials combined b FC-004 Pivotal Phase 3 clinical trial c Sorted on Total Raplixa + Gelatin subjects d R+G = Raplixa + Gelatin Sponge

G = Gelatin Sponge Alone Phase 2 a Phase 3 b Total c N (%) of Patients Preferred Term R+G d (N=86) G d (N=39) R+G d (N=480) G d (N=239) R+G d (N=566) G d (N=278) Procedural pain 40 (47) 16 (41) 257 (54) 134 (56) 297 (52) 150 (54) Nausea 26 (30) 13 (33) 120 (25) 48 (20) 146 (26) 61 (22) Constipation 21 (24) 9 (23) 72 (15) 31 (13) 93 (16) 40 (14) Incision site pain 5 (6) 3 (8) 63 (13) 32 (13) 68 (12) 35 (13) Pyrexia 7 (8) 5 (13) 37 (8) 11 (5) 44 (8) 16 (6) Anemia 4 (5) 2 (5) 33 (7) 17 (7) 37 (7) 19 (7) Vomiting 11 (13) 2 (5) 26 (5) 12 (5) 37 (7) 14 (5) Hypotension 2 (2) 2 (5) 38 (8) 16 (7) 40 (7) 18 (6) Pruritus 3 (3) 1 (3) 33 (7) 8 (3) 36 (6) 9 (3) Hypertension 1 (1) 0 25 (5) 10 (4) 26 (5) 10 (4) Immunogenicity The incidence of antibody formation in the Phase 3 trial was

evaluated.

Antibodies were detectable at baseline in 9/440 of Raplixa-treated patients (2 %) and 9/222 of gelatin sponge-treated patients (4 %).

Nine of 440 patients (2 %) in the Raplixa group and 6 of 222 patients (3 %) in the gelatin sponge alone group developed anti-thrombin antibodies (non-neutralizing) during the trial.

The clinical significance of these antibodies is not known.

Anti-fibrinogen antibodies were not detected pre - or post-treatment in any subjects that were positive for anti-thrombin antibodies.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

For these reasons, comparison of the incidence of antibodies to Raplixa with the incidence of antibodies to other products may be misleading.

Usage information

Dosing and administration

2 DOSAGE AND ADMINISTRATION For topical use only.

Do not reconstitute.

Use within one hour of opening.

For topical use only.

Do not reconstitute.

Use within one hour after opening.

The required dose of Raplixa depends on the size of the bleeding area.

The maximum total dose of Raplixa per surgery is 3 grams.

(2) Applying to the surface of bleeding tissue only, administer Raplixa directly from the vial or using the RaplixaSpray delivery device.

Raplixa may be used at multiple bleeding sites in the same patient.

Use no more than two vials of Raplixa with the RaplixaSpray device.

To administer a third vial, open a new device.

(2) 2.1 Dose The required amount of Raplixa needed to stop bleeding varies and is based on the size of the bleeding area to be treated.

The maximum total dose of Raplixa per surgery is 3 grams.

In clinical trials, it was demonstrated that smaller bleeding sites covering an area of less than 10 cm2 used 0.5 gram to 1.0 gram of Raplixa.

Larger bleeding sites covering an area of 10-100 cm2 used 1.0 to 2.0 grams of Raplixa to stop bleeding.

Using the RaplixaSpray device, 1.0 gram can cover a 100 cm2 bleeding surface area.

The required dose of Raplixa depends on the size of the bleeding area to be treated according to Table 1 below.

Table 1: Guideline for Raplixa Application Maximum Surface Area Direct Application from Vial Maximum Surface Area Application Using RaplixaSpray Device Raplixa Package Size 25 cm2 50 cm2 0.5 g 50 cm2 100 cm2 1 g 100 cm2 200 cm2 2 g 2.2 Administration Applying to the surface of bleeding tissue only, administer Raplixa directly from the vial or using the RaplixaSpray device.

Raplixa may be used at multiple bleeding sites in the same patient.

Use no more than two vials of Raplixa with the RaplixaSpray device.

To administer a third vial, open a new device.

Direct Application of Raplixa with Absorbable Gelatin Sponge (USP) Note:

Refer to Absorbable Gelatin Sponge (USP) labeling for complete instructions for use. 1.

Open the pouch and take out the Raplixa vial following standard sterile technique to ensure that 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 Raplixa gently onto bleeding site and apply gentle pressure with gelatin sponge using sterile gauze.

OR 1.

Remove stopper and sprinkle a thin layer of Raplixa gently onto a pre-wetted gelatin sponge and place onto the bleeding site with gentle pressure using sterile gauze.

Preparation and Application of Raplixa Using the RaplixaSpray Device with Absorbable Gelatin Sponge (USP) Note:

Refer to the RaplixaSpray Device labeling for complete instructions for use.

Refer to Absorbable Gelatin Sponge (USP) labeling for complete instructions for use.

1.

Prepare the pressure regulator (Air or CO2) according to the manufacturer 's instructions for use.

2.

Open the pouch and take out the Raplixa vial following standard sterile technique to ensure that 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 Raplixa within 10-60 seconds.

13.

Immediately after Raplixa application, place a gelatin sponge, trimmed to the approximate size, on top of the Raplixa 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 two vials of Raplixa with the RaplixaSpray device.

15.

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

Use in special populations

8 USE IN SPECIFIC POPULATIONS Pregnancy: No human or animal data.

Use only if clearly needed.

(8.1) 8.1 Pregnancy Animal reproduction studies have not been conducted with Raplixa.

It is also not known whether Raplixa can cause fetal harm when administered to pregnant women or can affect reproductive capacity.

Raplixa should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers It is not known whether Raplixa is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when administering to a nursing woman.

8.4 Pediatric Use Safety and effectiveness of Raplixa in pediatric patients has not been established.

8.5 Geriatric Use Clinical trials included 207/566 subjects of 65 years of age or older who were treated with Raplixa.

No differences in safety and efficacy were observed between elderly and younger patients.

Pregnancy and lactation
8.3 Nursing Mothers It is not known whether Raplixa is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when administering to a nursing woman.

More information

Category Value
Authorisation number BLA125523
Agency product number N94833051K
Orphan designation No
Product NDC 62238-008
Date Last Revised 23-06-2015
Type HUMAN PRESCRIPTION DRUG
RXCUI 1655054
Marketing authorisation holder ProFibrix BV

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