CLASSES
Blood Coagulation Factors
BOXED WARNING
Disseminated intravascular coagulation (DIC), myocardial infarction, thromboembolism
Anti-inhibitor coagulant complex (AICC) is contraindicated in patients with disseminated intravascular coagulation (DIC) and patients with acute thrombosis or embolism, including myocardial infarction. Thromboembolism, including DIC, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have been reported following AICC administration. Many of these events occurred after high doses (more than 200 units/kg/day) and/or in patients with thrombotic risk factors. Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of thrombosis due to predisposing coagulopathy or circulating tissue factor. Potential benefit of treatment with AICC should be weighed against risk for thromboembolic event. Monitor patients receiving AICC more than 100 units/kg for signs and symptoms of DIC, acute coronary ischemia, and other thromboembolic events. If signs or symptoms such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain occur, discontinue the AICC infusion and initiate appropriate diagnostic and therapeutic measures.
DESCRIPTION
Derived from human plasma; similar to PCCs or factor IX complexes with increased amount of activated and precursor vitamin K-dependent clotting factors (factors II, VII, IX, and X)
Used for coagulation factor bypass therapy in patients with hemophilia with inhibitors or in patients with acquired inhibitors to other clotting factors
Controls bleeding in about 80% to 90% of patients with 1 or 2 doses
COMMON BRAND NAMES
FEIBA, FEIBA NF, Feiba NF Immuno, FEIBA VH Immuno
HOW SUPPLIED
FEIBA/FEIBA NF/Feiba NF Immuno/FEIBA VH Immuno Intravenous Inj Pwd F/Sol
DOSAGE & INDICATIONS
For the control and prevention of bleeding episodes (i.e., hemorrhage, hemarthrosis), perioperative management (surgical bleeding), and routine bleeding prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or hemophilia B with inhibitors or patients with acquired inhibitors to other factors including patients with factor VII deficiency† or von Willebrand's disease†.
NOTE: 1 unit of activity is defined as the amount of FEIBA that shortens the aPTT of high titer factor VIII inhibitor reference plasma to 50% of the blank value.
NOTE: FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to factor VIII or factor IX.
For treatment of joint hemorrhage.
Intravenous dosage
Adults 18 to 64 years
50 to 100 units/kg/dose IV every 12 hours until pain and acute disabilities are improved.
Infants, Children, and Adolescents
50 to 100 units/kg/dose IV every 12 hours until pain and acute disabilities are improved.
For treatment of mucous membrane bleeding.
Intravenous dosage
Adults 18 to 64 years
50 to 100 units/kg/dose IV every 6 hours for at least 1 day or until bleeding is resolved.
Infants, Children, and Adolescents
50 to 100 units/kg/dose IV every 6 hours for at least 1 day or until bleeding is resolved.
For the treatment of soft tissue hemorrhage.
Intravenous dosage
Adults 18 to 64 years
100 units/kg/dose IV every 12 hours until resolution of bleeding.
Infants, Children, and Adolescents
100 units/kg/dose IV every 12 hours until resolution of bleeding.
For the treatment of severe hemorrhage (CNS bleeding).
Intravenous dosage
Adults 18 to 64 years
100 units/kg/dose IV every 6 to 12 hours until resolution of bleeding.
Infants, Children, and Adolescents
100 units/kg/dose IV every 6 to 12 hours until resolution of bleeding.
For preoperative management of surgical bleeding.
Intravenous dosage
Adults 18 to 64 years
50 to 100 units/kg/dose IV as a single dose immediately prior to surgery.
Infants, Children, and Adolescents
50 to 100 units/kg/dose IV as a single dose immediately prior to surgery.
For postoperative management of surgical bleeding.
Intravenous dosage
Adults 18 to 64 years
50 to 100 units/kg IV every 6 to 12 hours until resolution of bleeding and healing are achieved.
Infants, Children, and Adolescents
50 to 100 units/kg/dose IV every 6 to 12 hours until resolution of bleeding and healing are achieved.
For routine prophylaxis.
Intravenous dosage
Adults 18 to 64 years
85 units/kg/dose IV every other day.
Infants, Children, and Adolescents
85 units/kg/dose IV every other day.
For rivaroxaban reversal†.
Intravenous dosage
Adults
30 units/kg IV over 15 minutes just prior to neurosurgery was reported in 1 geriatric patient receiving rivaroxaban 20 mg daily who developed a subdural hematoma with a midline shift after a fall.
For dabigatran reversal†.
Intravenous dosage
Adults
25 units/kg (rounded to vial size, 27.5 units/kg), 26 units/kg, 42 units/kg, 50 units/kg, or 100 units/kg IV once doses are described in various case reports. Following an initial dose of 26 units/kg IV, a second dose of 16 units/kg IV was administered in a single case due to concerns for rebleeding.
†Indicates off-label use
MAXIMUM DOSAGE
Adults
100 units/kg/dose IV or 200 units/kg/day IV.
Geriatric
Safety and efficacy have not been established.
Adolescents
100 units/kg/dose IV or 200 units/kg/day IV.
Children
100 units/kg/dose IV or 200 units/kg/day IV.
Infants
100 units/kg/dose IV or 200 units/kg/day IV.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
No dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be colorless to slightly yellowish. Do not use if particulate matter or discoloration is observed.
Reconstitution
Use aseptic technique throughout the entire reconstitution process. Allow concentrate and diluent vials to reach room temperature.
Remove caps from both vials. Wipe the rubber stoppers with a sterile alcohol swab and allow it to dry.
Peel away lid of BAXJECT II Hi-Flow device taking care not to touch the inside. Do not remove the device from the package. Do not touch the clear spike.
Turn the package over and insert the clear plastic spike through diluent stopper by pressing straight down. Grip the device package at the edges and pull the package off the device. Do not remove the blue protective cap from the device. Do not touch the purple spike.
Turn the system over, so that the diluent vial is on top. Quickly insert the purple spike of the device fully into the concentrate vial. The vacuum will draw the diluent into the vial. The connection of the 2 vials should be done quickly to close the open fluid pathway created by the first insertion of the spike to the diluent vial.
Gently swirl until completely dissolved. If not dissolved completely, active material will not pass through the device filter. Do not shake.
Storage: Administer within 3 hours of reconstitution. Do not refrigerate after reconstitution.
Intravenous Administration
Flush venous access lines with isotonic saline prior to and after infusion. Do not administer in the same tubing or container with other medicinal products.
Use plastic luer-lock syringes. Protein such as anti-inhibitor coagulant complex tends to stick to the surface of all-glass syringes.
Remove the blue protective cap from the BAXJECT II Hi-Flow device. Tightly connect the syringe to the device by turning the syringe in clockwise direction until stop position.
Invert the system so that the dissolved concentrate product is on top and draw the dissolved product into the syringe by pulling the plunger back slowly to avoid foaming. Ensure the tight connection between the device and syringe is maintained.
Disconnect the syringe.
Attach a suitable needle and inject or infuse intravenously at a rate not to exceed 2 units/kg/minute.
STORAGE
FEIBA:
- Do not freeze
- Protect from light
- Reconstituted product should be used within 3 hours
- Store at room temperature (up to 77 degrees F)
- Store in original package until time of use
FEIBA NF:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion. Do not store for later use.
- Do not freeze
- May be stored at room temperature not exceeding 77 degrees F for up to 6 months
- Product stored at controlled room temperature should not be returned to a refrigerator
- Reconstituted product should be used within 3 hours
- Store between 35 to 46 degrees F
Feiba NF Immuno:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not refrigerate reconstituted product
- Protect from freezing
- Protect from light
- Reconstituted product should be used within 3 hours
- Store at room temperature (up to 77 degrees F)
- Store in original package until time of use
FEIBA VH Immuno:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not refrigerate reconstituted product
- May be stored at room temperature not exceeding 77 degrees F for up to 6 months
- Product stored at controlled room temperature should not be returned to a refrigerator
- Protect from freezing
- Refrigerate (between 36 and 46 degrees F)
CONTRAINDICATIONS / PRECAUTIONS
General Information
Anti-inhibitor coagulant complex is contraindicated in patients with known anaphylactic or severe hypersensitivity reactions to anti-inhibitor coagulant complex or any of its components, including factors of the kinin generating system.
Disseminated intravascular coagulation (DIC), myocardial infarction, thromboembolism
Anti-inhibitor coagulant complex (AICC) is contraindicated in patients with disseminated intravascular coagulation (DIC) and patients with acute thrombosis or embolism, including myocardial infarction. Thromboembolism, including DIC, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have been reported following AICC administration. Many of these events occurred after high doses (more than 200 units/kg/day) and/or in patients with thrombotic risk factors. Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of thrombosis due to predisposing coagulopathy or circulating tissue factor. Potential benefit of treatment with AICC should be weighed against risk for thromboembolic event. Monitor patients receiving AICC more than 100 units/kg for signs and symptoms of DIC, acute coronary ischemia, and other thromboembolic events. If signs or symptoms such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain occur, discontinue the AICC infusion and initiate appropriate diagnostic and therapeutic measures.
Viral infection
Anti-inhibitor coagulant complex (AICC) is derived from human plasma and may therefore carry a risk of transmitting viral infection, and theoretically, the Creutzfeldt-Jakob disease agent. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents; however, none of the processes are completely effective. All infections thought to have been transmitted by AICC should be reported to the manufacturer and/or the FDA (1-800-FDA-1088 or www.fda.gov/medwatch).
Thrombocytopenia
An inadequate response to anti-inhibitor coagulant complex (AICC) may be seen in patients with thrombocytopenia or abnormal platelet function which were present prior to treatment with AICC.
Pregnancy
It is not known whether anti-inhibitor coagulant complex (AICC) can affect reproduction capacity or cause fetal harm when administered during human pregnancy. Animal studies have not been conducted. Use AICC during pregnancy only if clearly needed.
Breast-feeding
There is no information regarding the presence of anti-inhibitor coagulant complex (AICC) in human milk, the effect on the breast-fed child, or the effects on milk production Because many drugs are excreted in human milk, exercise caution when AICC is administered to a breast-feeding mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[41546] If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Children
In some cases, laboratory tests such as activated thromboplastin time (aPTT) may not correlate with clinical response of anti-inhibitor complex (AICC) treatment. Hemostatic improvement may occur without a reduction in aPTT. However, a shortened prothrombin time (PT) would be expected. Attempts to normalize these parameters by increasing the doses of AICC is not recommended due to the increased risk of disseminated intravascular coagulation (DIC) associated with increased doses. In children, fibrinogen levels should be determined prior to and monitored during AICC treatment.
ADVERSE REACTIONS
Severe
angioedema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
Moderate
anemia / Delayed / 5.6-5.6
wheezing / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
infusion-related reactions / Rapid / Incidence not known
hypertension / Early / Incidence not known
hot flashes / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
dyspnea / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
Mild
diarrhea / Early / 5.6-5.6
vomiting / Early / 5.6-5.6
nausea / Early / 5.6-5.6
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
chills / Rapid / Incidence not known
fever / Early / Incidence not known
infection / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
dizziness / Early / Incidence not known
malaise / Early / Incidence not known
drowsiness / Early / Incidence not known
dysgeusia / Early / Incidence not known
flushing / Rapid / Incidence not known
DRUG INTERACTIONS
Aminocaproic Acid: (Major) Use of aminocaproic acid within approximately 6 to 12 hours after the administration of anti-inhibitor coagulant complex (human) is not recommended, due to the increased risk of thrombosis.
Emicizumab: (Moderate) Consider the benefits and risks if anti-inhibitor coagulant complex (human), also known as activated prothrombin complex concentrate (aPCC), must be used in a patient receiving emicizumab. If aPCC is used, monitor for thrombotic microangiopathy (TMA) and thrombosis. Discontinue aPCC and interrupt emicizumab if clinical symptoms or laboratory findings consistent with TMA or thrombosis occur and manage as clinically indicated. Consider the benefits and risks of resuming emicizumab after resolution of TMA or thrombosis on a case-by-case basis. TMA and thrombotic events have been reported when, on average, a cumulative amount of more than 100 units/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving emicizumab. The potential for interaction may persist for up to 6 months after the last emicizumab dose.
Factor VIIa, Recombinant: (Major) Avoid concomitant use of recombinant factor VIIa and activated prothrombin complex concentrates (aPCCs) due to the increased risk for thrombotic events.
Tranexamic Acid: (Major) Use of tranexamic acid within approximately 6 to 12 hours after the administration of anti-inhibitor coagulant complex (human) is not recommended, due to the increased risk of thrombosis.
PREGNANCY AND LACTATION
Pregnancy
It is not known whether anti-inhibitor coagulant complex (AICC) can affect reproduction capacity or cause fetal harm when administered during human pregnancy. Animal studies have not been conducted. Use AICC during pregnancy only if clearly needed.
There is no information regarding the presence of anti-inhibitor coagulant complex (AICC) in human milk, the effect on the breast-fed child, or the effects on milk production Because many drugs are excreted in human milk, exercise caution when AICC is administered to a breast-feeding mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[41546] If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
MECHANISM OF ACTION
Anti-inhibitor coagulant complex (AICC) provides activated coagulation factors to restore hemostasis in patients with inhibitors to certain coagulation factors. The actual active component of AICC has not been identified and may include activated factor VII, activated factor X with or without phospholipid or a combination of factors. Anti-inhibitor coagulant complex may induce a hypercoagulable state leading thrombosis or disseminated intravascular coagulation due to the administration of activated factors, presence of circulating tissue factor and the underlying coagulopathy. Administration of AICC results in changes in coagulation parameters, most notably prothrombin time (PT); however, the degree of change may not reflect the actual clinical effect.
PHARMACOKINETICS
Anti-inhibitor coagulant complex (AICC) is administered intravenously. The onset of activity is dependent upon the amount of activated factor present, type of inhibitor present, and the half-lives of the factors. The half-lives of the factors present in AICC are as follows: factor II, more than 60 hours; factor VII, 4 to 6 hours; factor IX, 20 to 24 hours; and factor X, 48 to 72 hours.