|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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====Dosage====
====Dosage====
40 International Units (IU) per kg body weight at a rate not to exceed 4 mL per minute
Adjust dose ±5 IU per kg to maintain 5% to 20% trough level of FXIII activity
|offLabelPedGuideSupport======Condition1=====
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
* Dosing Information
<!--Contraindications-->
|contraindications=* Corifact is contraindicated in patients with known anaphylactic or severe systemic reactions to human plasma-derived products
:* Dosage
<!--Warnings-->
|warnings=* Hypersensitivity
Hypersensitivity reactions have been observed with Corifact. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, immediately discontinue administration [see PATIENT COUNSELING INFORMATION (17)] and institute appropriate treatment.
=====Condition2=====
5.2 Immunogenicity
Development of inhibitory antibodies against FXIII has been detected in patients receiving Corifact. Monitor patients for development of inhibitory antibodies. Presence of inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs while receiving prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
5.3 Thromboembolic Risk
Thromboembolic complications have been reported. Monitor patients with known risk factors for thrombotic events.
<!--Contraindications-->
|contraindications=* Condition1
<!--Warnings-->
5.4 Transmission of Infectious Agents
|warnings=* Description
Corifact is made from human plasma. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.
====Precautions====
All infections thought by a physician to have been possibly transmitted by this product are to be reported by the physician or other healthcare provider to the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
* Description
5.5 Monitoring Laboratory Tests
Monitor patient's trough FXIII activity level during treatment with Corifact [see ADMINISTRATION (2.2)].
If breakthrough bleeding occurs, or if expected peak plasma FXIII activity levels are not attained, perform an investigation to determine the presence of FXIII inhibitory antibodies
<!--Adverse Reactions-->
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|clinicalTrials=The most common adverse reactions reported in frequency >1% are joint inflammation, hypersensitivity, rash, pruritus, erythema, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, and increased blood lactate dehydrogenase.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
The serious adverse reactions, reported in one subject each (frequency 0.5%), were hypersensitivity, acute ischemia, and neutralizing antibodies against FXIII.
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 cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Twelve clinical studies included a total of 188 subjects, 108 subjects were <16 years of age [see USE IN SPECIFIC POPULATIONS (8.4)] and a total of approximately 4314 infusions of Corifact were administered in the studies.
=====Metabolic and Nutritional=====
Efficacy and Safety Study
A 12-month, prospective, open-label, multicenter efficacy and safety study was conducted in 25 males and 16 females ranging in age from less than 1 year to 42 years old (2 infants, 8 children, 8 adolescents, and 23 adults). There were no reports of deaths, life-threatening events, or adverse events that led to discontinuation or withdrawal from the study. Four subjects received FXIII in the peri-operative setting, and no treatment-related AEs were reported. An additional subject was pre-treated with plasma and experienced a hypersensitivity reaction.
6.2 Immunogenicity
A case of neutralizing antibodies against FXIII was reported in the postmarketing clinical study. The patient received prophylactic treatment with Corifact for ten years. Concomitant medications included interferon for hepatitis C infection. This patient presented with bruising, and post-infusion FXIII levels were found to be lower than expected. Over several weeks, FXIII recovery values decreased, so the dose and frequency of treatments were increased. Neutralizing antibodies to FXIII were detected, interferon treatment was discontinued, and the subject underwent plasmapheresis. Within a month, neutralizing antibodies were no longer detectable, FXIII recovery levels improved, and the previous prophylactic regimen was resumed.
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
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<!--Use in Specific Populations-->
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|FDAPregCat=C
|useInPregnancyFDA=* Animal reproduction studies have not been conducted with Corifact. Safety and effectiveness in pregnancy have not been established. It is also not known whether Corifact can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Corifact should be given to a pregnant woman only if clearly needed.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=Corifact has not been studied for use during labor and delivery. Safety and effectiveness in labor and delivery is unknown.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInNursing=It is not known whether Corifact is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Corifact is administered to a nursing woman.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInPed=Of the 188 subjects in the Corifact clinical studies, 108 were subjects <16 years of age at the time of enrollment
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
: [[File:Fac VIII peds.png|none|400px]]
In the pharmacokinetic study [see CLINICAL PHARMACOLOGY (12.3)], 5 of the 14 subjects ranged in age from 2 to <16 years. Subjects less than 16 years had a shorter half-life (5.7 ± 1.00 days) and faster clearance (0.29 ± 0.12 mL/hr/kg) compared to adults (half-life: 7.1 ± 2.74 days, clearance: 0.22 ± 0.07 mL/hr/kg). Dose adjustments may be needed for patients <16 years of age. There were no differences in the safety profile in children as compared to adults.
|useInGeri=The safety and efficacy of Corifact in the geriatric population have not been established.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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<!--Administration and Monitoring-->
<!--Administration and Monitoring-->
|administration=* Oral
|administration=* Intravenous
|monitoring=* Monitor patient's FXIII activity levels during and after surgery
* Intravenous
* Monitor patients for development of inhibitory antibodies.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Monitor patient's trough FXIII activity level during treatment with Corifact
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
<!--Overdosage-->
|overdose====Acute Overdose===
|overdose=There is limited information regarding <i>Overdose</i> of {{PAGENAME}} in the drug label.
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
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Overview
Factor XIII concentrate is a hemostatic that is FDA approved for the treatment of congenital Factor XIII deficiency. Common adverse reactions include joint inflammation, hypersensitivity, rash, pruritus, erythema, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, and increased blood lactate dehydrogenase.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Corifact is a Factor XIII concentrate indicated for adult and pediatric patients with congenital Factor XIII deficiency for:
Routine prophylactic treatment
Peri-operative management of surgical bleeding
Dosage
40 International Units (IU) per kg body weight at a rate not to exceed 4 mL per minute
Adjust dose ±5 IU per kg to maintain 5% to 20% trough level of FXIII activity as provided in the example below
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Factor XIII concentrate in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Factor XIII concentrate in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Indications
Corifact is a Factor XIII Concentrate indicated for routine prophylactic treatment and peri-operative management of surgical bleeding in adult and pediatric patients with congenital FXIII deficiency.
Dosage
40 International Units (IU) per kg body weight at a rate not to exceed 4 mL per minute
Adjust dose ±5 IU per kg to maintain 5% to 20% trough level of FXIII activity
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Factor XIII concentrate in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Factor XIII concentrate in pediatric patients.
Contraindications
Corifact is contraindicated in patients with known anaphylactic or severe systemic reactions to human plasma-derived products
Warnings
Hypersensitivity
Hypersensitivity reactions have been observed with Corifact. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, immediately discontinue administration [see PATIENT COUNSELING INFORMATION (17)] and institute appropriate treatment.
5.2 Immunogenicity
Development of inhibitory antibodies against FXIII has been detected in patients receiving Corifact. Monitor patients for development of inhibitory antibodies. Presence of inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs while receiving prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.
5.3 Thromboembolic Risk
Thromboembolic complications have been reported. Monitor patients with known risk factors for thrombotic events.
5.4 Transmission of Infectious Agents
Corifact is made from human plasma. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.
All infections thought by a physician to have been possibly transmitted by this product are to be reported by the physician or other healthcare provider to the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
5.5 Monitoring Laboratory Tests
Monitor patient's trough FXIII activity level during treatment with Corifact [see ADMINISTRATION (2.2)].
If breakthrough bleeding occurs, or if expected peak plasma FXIII activity levels are not attained, perform an investigation to determine the presence of FXIII inhibitory antibodies
Adverse Reactions
Clinical Trials Experience
The most common adverse reactions reported in frequency >1% are joint inflammation, hypersensitivity, rash, pruritus, erythema, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, and increased blood lactate dehydrogenase.
The serious adverse reactions, reported in one subject each (frequency 0.5%), were hypersensitivity, acute ischemia, and neutralizing antibodies against FXIII.
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 cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Twelve clinical studies included a total of 188 subjects, 108 subjects were <16 years of age [see USE IN SPECIFIC POPULATIONS (8.4)] and a total of approximately 4314 infusions of Corifact were administered in the studies.
Efficacy and Safety Study
A 12-month, prospective, open-label, multicenter efficacy and safety study was conducted in 25 males and 16 females ranging in age from less than 1 year to 42 years old (2 infants, 8 children, 8 adolescents, and 23 adults). There were no reports of deaths, life-threatening events, or adverse events that led to discontinuation or withdrawal from the study. Four subjects received FXIII in the peri-operative setting, and no treatment-related AEs were reported. An additional subject was pre-treated with plasma and experienced a hypersensitivity reaction.
6.2 Immunogenicity
A case of neutralizing antibodies against FXIII was reported in the postmarketing clinical study. The patient received prophylactic treatment with Corifact for ten years. Concomitant medications included interferon for hepatitis C infection. This patient presented with bruising, and post-infusion FXIII levels were found to be lower than expected. Over several weeks, FXIII recovery values decreased, so the dose and frequency of treatments were increased. Neutralizing antibodies to FXIII were detected, interferon treatment was discontinued, and the subject underwent plasmapheresis. Within a month, neutralizing antibodies were no longer detectable, FXIII recovery levels improved, and the previous prophylactic regimen was resumed.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Factor XIII concentrate in the drug label.
Animal reproduction studies have not been conducted with Corifact. Safety and effectiveness in pregnancy have not been established. It is also not known whether Corifact can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Corifact should be given to a pregnant woman only if clearly needed.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Factor XIII concentrate in women who are pregnant.
Labor and Delivery
Corifact has not been studied for use during labor and delivery. Safety and effectiveness in labor and delivery is unknown.
Nursing Mothers
It is not known whether Corifact is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Corifact is administered to a nursing woman.
Pediatric Use
Of the 188 subjects in the Corifact clinical studies, 108 were subjects <16 years of age at the time of enrollment
In the pharmacokinetic study [see CLINICAL PHARMACOLOGY (12.3)], 5 of the 14 subjects ranged in age from 2 to <16 years. Subjects less than 16 years had a shorter half-life (5.7 ± 1.00 days) and faster clearance (0.29 ± 0.12 mL/hr/kg) compared to adults (half-life: 7.1 ± 2.74 days, clearance: 0.22 ± 0.07 mL/hr/kg). Dose adjustments may be needed for patients <16 years of age. There were no differences in the safety profile in children as compared to adults.
Geriatic Use
The safety and efficacy of Corifact in the geriatric population have not been established.
Gender
There is no FDA guidance on the use of Factor XIII concentrate with respect to specific gender populations.
Race
There is no FDA guidance on the use of Factor XIII concentrate with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Factor XIII concentrate in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Factor XIII concentrate in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Factor XIII concentrate in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Factor XIII concentrate in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravenous
Monitoring
Monitor patient's FXIII activity levels during and after surgery
Monitor patients for development of inhibitory antibodies.
Monitor patient's trough FXIII activity level during treatment with Corifact
IV Compatibility
There is limited information regarding IV Compatibility of Factor XIII concentrate in the drug label.
Overdosage
There is limited information regarding Overdose of Factor XIII concentrate in the drug label.
Pharmacology
There is limited information regarding Factor XIII concentrate Pharmacology in the drug label.
