RECOTHROM
Generic: THROMBIN TOPICAL RECOMBINANT
Basic Information
Manufacturer
Baxter Healthcare Corporation
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
54885644-e51e-4263-aadb-366abaeb56a3
Indications & Usage
1 INDICATIONS AND USAGE RECOTHROM 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.
RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.
RECOTHROM 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.
(1) RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.
(1)
RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.
RECOTHROM 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.
(1) RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.
(1)
Adverse Reactions
6 ADVERSE REACTIONS Thromboembolic adverse reactions were reported in 6% of surgical patients treated with RECOTHROM Thrombin topical (Recombinant) in all completed clinical trials (N=644) [see Warnings and Precautions (5.1) ] .
Antibody formation to RECOTHROM occurred in <1% of patients.
None of the antibodies detected neutralized native human thrombin [see Adverse Reactions (6.2) ] .
• The most common adverse reaction (incidence 6%) was thromboembolic events.
(5.1 , 6) • Antibody formation to RECOTHROM Thrombin topical (Recombinant) occurred in <1% of patients.
None of the antibodies detected neutralized native human thrombin.
(6.2) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 RECOTHROM Thrombin topical (Recombinant) applied with absorbable gelatin sponge and applied with a spray applicator.
A total of 644 patients were exposed to RECOTHROM in these studies.
RECOTHROM Thrombin topical (Recombinant) Used in Conjunction with Absorbable Gelatin Sponge Four hundred eleven (411) patients were treated in a randomized, double-blind, controlled trial that compared RECOTHROM to bovine thrombin.
Both thrombins were applied with a gelatin sponge in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access.
1 The incidence of thromboembolic adverse reactions was similar between the RECOTHROM and bovine thrombin treatment groups (see Table 1 ).
Table 1: Incidence of Adverse Reactions with RECOTHROM Thrombin topical (Recombinant) and Bovine Thrombin Adverse Reaction Category RECOTHROM (N=205) n (%) Bovine Thrombin THROMBIN-JMI Thrombin, Topical (Bovine) (N=206) n (%) Thromboembolic events 11 (5%) 12 (6%) In an open-label, single-group trial (N=209), patients with documented or highly likely prior exposure to bovine thrombin within the previous three years were treated with RECOTHROM when undergoing surgeries (spinal, peripheral arterial bypass, or arteriovenous graft formation for hemodialysis access).
2 The incidence of thromboembolic adverse reactions in this study was 9%.
In an open-label, single-group trial of re-exposure to RECOTHROM (N=31), patients with documented prior exposure to RECOTHROM were treated with RECOTHROM during surgery (spinal, peripheral arterial bypass, arteriovenous graft formation, or other procedures).
3 The incidence of thromboembolic adverse reactions in this study was 3%.
In other randomized, double-blind trials across a range of surgical settings (N=130; spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access), the safety of RECOTHROM (n=88 patients) was compared to placebo (RECOTHROM excipients reconstituted with sterile 0.9% sodium chloride, USP) (n=42 patients).
The incidence of thromboembolic adverse reactions in this study was 5% for RECOTHROM and 12% for placebo.
RECOTHROM Thrombin topical (Recombinant) Applied with Spray Applicator RECOTHROM was applied with a spray applicator in two open-label clinical trials: a single-group trial in adult and pediatric burn patients (N=72; ≤16 years of age, (n=4) and ≥17 years of age, (n=68)) treated with RECOTHROM applied to the wound excision site prior to autologous skin grafting 4 ; and in a single-group trial in pediatric patients (one month to 17 years of age) undergoing synchronous burn wound excision and autologous skin grafting (N=30; ≤16 years of age, (n=26); ≥17 years of age, (n=4)).
5 In the first study, the incidence of thromboembolic adverse reactions was 1%.
In the second study, there were no reported thromboembolic adverse reactions [see Use in Specific Populations (8.4) ] .
6.2 Immunogenicity The detection of antibody formation is highly dependent upon the sensitivity and specificity of the assay.
The absolute immunogenicity rates reported here are difficult to compare with the results from other products due to differences in assay methodology, patient populations, and other underlying factors.
The potential for development of antibodies to RECOTHROM Thrombin topical (Recombinant) was evaluated in multiple clinical trials and included patients with a single exposure to RECOTHROM as well as patients who were re-exposed to RECOTHROM during a subsequent surgical procedure.
Only patients with both baseline and post-treatment antibody specimens available were evaluated for the development of specific anti-RECOTHROM product antibodies, which was defined as seroconversion or a ≥1.0 titer unit (≥10-fold) increase in antibody levels after study treatment.
Five of 609 (0.8%; 95% CI, 0.4%-2.8%) evaluable patients developed specific anti-RECOTHROM product antibodies.
None of these antibodies were found to neutralize native human thrombin.
There was no difference in anti-RECOTHROM product antibody formation incidence among patients exposed to RECOTHROM applied with absorbable gelatin sponge, USP or with spray applicator.
In a clinical trial comparing RECOTHROM to bovine thrombin (N=411; n=398 antibody evaluable) for the development of specific anti-product antibodies, blood samples were collected at baseline and at Day 29 in both treatment groups and were analyzed by ELISA.
1 At baseline, 1.5% of RECOTHROM patients (n=3/198) had positive anti-product antibody titers compared with 5% of bovine thrombin patients (n=10/200).
Of these patients, none of the RECOTHROM group and eight in the bovine thrombin group exhibited ≥1.0 titer unit (≥10-fold) increases in anti-product antibody levels after study treatment.
At Day 29, three of 198 (1.5%; 95% CI, 0%-4%) patients in the RECOTHROM group developed specific anti-product antibodies (one patient also developed anti-CHO host cell protein antibodies); 43 of 200 patients in the bovine thrombin group (22%; 95% CI, 16%-28%) developed specific antibodies to bovine thrombin product.
Treatment with RECOTHROM resulted in a statistically significant lower incidence of specific anti-product antibody development.
Because the study was not powered to detect a difference in clinical outcomes attributable to antibody formation, no conclusions can be drawn regarding the clinical significance of the difference in antibody formation based on the results of this study.
None of the antibodies in the RECOTHROM group neutralized native human thrombin.
Antibodies against bovine thrombin product were not tested for neutralization of native human thrombin.
In a trial of patients with a high likelihood of prior exposure to bovine thrombin, 15.6% of patients (n=32/205) had anti-bovine thrombin product antibodies and 2% of patients (n=4/200) had anti-RECOTHROM product antibodies at baseline.
2 Following treatment, none of the 200 evaluable patients (patients for whom post-treatment specimens were available) developed antibodies to RECOTHROM.
In a trial of patients previously exposed to RECOTHROM, 31 patients were re-exposed to RECOTHROM during a subsequent surgery.
3 None of the evaluable patients (n=30) had anti- RECOTHROM product antibodies at baseline and none developed antibodies at Day 29.
In a trial of RECOTHROM, including 26 pediatric patients (aged one month to 16 years) and four patients 17 years of age, one patient without prior thrombin exposure had pre-existing anti-RECOTHROM product antibodies at baseline.
5 None of the 27 evaluable patients developed anti-RECOTHROM product antibodies at Day 29.
Antibody formation to RECOTHROM occurred in <1% of patients.
None of the antibodies detected neutralized native human thrombin [see Adverse Reactions (6.2) ] .
• The most common adverse reaction (incidence 6%) was thromboembolic events.
(5.1 , 6) • Antibody formation to RECOTHROM Thrombin topical (Recombinant) occurred in <1% of patients.
None of the antibodies detected neutralized native human thrombin.
(6.2) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 RECOTHROM Thrombin topical (Recombinant) applied with absorbable gelatin sponge and applied with a spray applicator.
A total of 644 patients were exposed to RECOTHROM in these studies.
RECOTHROM Thrombin topical (Recombinant) Used in Conjunction with Absorbable Gelatin Sponge Four hundred eleven (411) patients were treated in a randomized, double-blind, controlled trial that compared RECOTHROM to bovine thrombin.
Both thrombins were applied with a gelatin sponge in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access.
1 The incidence of thromboembolic adverse reactions was similar between the RECOTHROM and bovine thrombin treatment groups (see Table 1 ).
Table 1: Incidence of Adverse Reactions with RECOTHROM Thrombin topical (Recombinant) and Bovine Thrombin Adverse Reaction Category RECOTHROM (N=205) n (%) Bovine Thrombin THROMBIN-JMI Thrombin, Topical (Bovine) (N=206) n (%) Thromboembolic events 11 (5%) 12 (6%) In an open-label, single-group trial (N=209), patients with documented or highly likely prior exposure to bovine thrombin within the previous three years were treated with RECOTHROM when undergoing surgeries (spinal, peripheral arterial bypass, or arteriovenous graft formation for hemodialysis access).
2 The incidence of thromboembolic adverse reactions in this study was 9%.
In an open-label, single-group trial of re-exposure to RECOTHROM (N=31), patients with documented prior exposure to RECOTHROM were treated with RECOTHROM during surgery (spinal, peripheral arterial bypass, arteriovenous graft formation, or other procedures).
3 The incidence of thromboembolic adverse reactions in this study was 3%.
In other randomized, double-blind trials across a range of surgical settings (N=130; spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access), the safety of RECOTHROM (n=88 patients) was compared to placebo (RECOTHROM excipients reconstituted with sterile 0.9% sodium chloride, USP) (n=42 patients).
The incidence of thromboembolic adverse reactions in this study was 5% for RECOTHROM and 12% for placebo.
RECOTHROM Thrombin topical (Recombinant) Applied with Spray Applicator RECOTHROM was applied with a spray applicator in two open-label clinical trials: a single-group trial in adult and pediatric burn patients (N=72; ≤16 years of age, (n=4) and ≥17 years of age, (n=68)) treated with RECOTHROM applied to the wound excision site prior to autologous skin grafting 4 ; and in a single-group trial in pediatric patients (one month to 17 years of age) undergoing synchronous burn wound excision and autologous skin grafting (N=30; ≤16 years of age, (n=26); ≥17 years of age, (n=4)).
5 In the first study, the incidence of thromboembolic adverse reactions was 1%.
In the second study, there were no reported thromboembolic adverse reactions [see Use in Specific Populations (8.4) ] .
6.2 Immunogenicity The detection of antibody formation is highly dependent upon the sensitivity and specificity of the assay.
The absolute immunogenicity rates reported here are difficult to compare with the results from other products due to differences in assay methodology, patient populations, and other underlying factors.
The potential for development of antibodies to RECOTHROM Thrombin topical (Recombinant) was evaluated in multiple clinical trials and included patients with a single exposure to RECOTHROM as well as patients who were re-exposed to RECOTHROM during a subsequent surgical procedure.
Only patients with both baseline and post-treatment antibody specimens available were evaluated for the development of specific anti-RECOTHROM product antibodies, which was defined as seroconversion or a ≥1.0 titer unit (≥10-fold) increase in antibody levels after study treatment.
Five of 609 (0.8%; 95% CI, 0.4%-2.8%) evaluable patients developed specific anti-RECOTHROM product antibodies.
None of these antibodies were found to neutralize native human thrombin.
There was no difference in anti-RECOTHROM product antibody formation incidence among patients exposed to RECOTHROM applied with absorbable gelatin sponge, USP or with spray applicator.
In a clinical trial comparing RECOTHROM to bovine thrombin (N=411; n=398 antibody evaluable) for the development of specific anti-product antibodies, blood samples were collected at baseline and at Day 29 in both treatment groups and were analyzed by ELISA.
1 At baseline, 1.5% of RECOTHROM patients (n=3/198) had positive anti-product antibody titers compared with 5% of bovine thrombin patients (n=10/200).
Of these patients, none of the RECOTHROM group and eight in the bovine thrombin group exhibited ≥1.0 titer unit (≥10-fold) increases in anti-product antibody levels after study treatment.
At Day 29, three of 198 (1.5%; 95% CI, 0%-4%) patients in the RECOTHROM group developed specific anti-product antibodies (one patient also developed anti-CHO host cell protein antibodies); 43 of 200 patients in the bovine thrombin group (22%; 95% CI, 16%-28%) developed specific antibodies to bovine thrombin product.
Treatment with RECOTHROM resulted in a statistically significant lower incidence of specific anti-product antibody development.
Because the study was not powered to detect a difference in clinical outcomes attributable to antibody formation, no conclusions can be drawn regarding the clinical significance of the difference in antibody formation based on the results of this study.
None of the antibodies in the RECOTHROM group neutralized native human thrombin.
Antibodies against bovine thrombin product were not tested for neutralization of native human thrombin.
In a trial of patients with a high likelihood of prior exposure to bovine thrombin, 15.6% of patients (n=32/205) had anti-bovine thrombin product antibodies and 2% of patients (n=4/200) had anti-RECOTHROM product antibodies at baseline.
2 Following treatment, none of the 200 evaluable patients (patients for whom post-treatment specimens were available) developed antibodies to RECOTHROM.
In a trial of patients previously exposed to RECOTHROM, 31 patients were re-exposed to RECOTHROM during a subsequent surgery.
3 None of the evaluable patients (n=30) had anti- RECOTHROM product antibodies at baseline and none developed antibodies at Day 29.
In a trial of RECOTHROM, including 26 pediatric patients (aged one month to 16 years) and four patients 17 years of age, one patient without prior thrombin exposure had pre-existing anti-RECOTHROM product antibodies at baseline.
5 None of the 27 evaluable patients developed anti-RECOTHROM product antibodies at Day 29.