Anti-inhibitor Coagulant Complex (Human)

• It is used to treat hemophilia.
• It is used to treat or prevent bleeding.

• If you have an allergy to anti-inhibitor coagulant complex or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have other blood or bleeding problems.
• If you have had a recent heart attack.
• If you have a blood clot, have ever had a blood clot, or have been told you are at risk of getting a blood clot.
• If you are taking any of these drugs: Aminocaproic acid or tranexamic acid.

This is not a list of all drugs or health problems that interact with anti-inhibitor coagulant complex.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take anti-inhibitor coagulant complex. This includes your doctors, nurses, pharmacists, and dentists.
• If you have a latex allergy, talk with your doctor.
• Allergic side effects may rarely happen.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Call the doctor right away if the normal dose does not work as well.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• Talk with the doctor before you travel. You will need to bring enough of this medicine for use during travel.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using anti-inhibitor coagulant complex while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• FEIBA

8 to 12 hours (based on thrombin generation) (Varadi 2003)

Half-Life Elimination

4 to 7 hours (based on thrombin generation) (Varadi 2003)

Acquired hemophilia with factor VIII or factor IX inhibitor titers >5 Bethesda units (BU)

Data from a retrospective evaluation in patients treated with anti-inhibitor coagulant complex (human) who had autoantibodies to factor VIII suggests that anti-inhibitor coagulant complex (human) may be beneficial for the treatment of this condition [Sallah 2004]. Additional data may be necessary to further define the role of anti-inhibitor coagulant complex (human) in this condition.

Based on international recommendations on the diagnosis and treatment of patients with acquired hemophilia A, the use of anti-inhibitor coagulant complex (human) is effective and recommended for the treatment of severe bleeding in patients with this condition [Huth-Kuhne 2009].

Intracranial hemorrhage associated with non-vitamin K antagonist anticoagulants

Based on the American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Management of Spontaneous Intracerebral Hemorrhage, the use of anti-inhibitor coagulant complex (human) (ie, activated prothrombin complex concentrate [PCC]) may be considered for the treatment of intracranial hemorrhage associated with dabigatran (if idarucizumab is unavailable) or oral direct factor Xa inhibitors (apixaban, edoxaban, or rivaroxaban) if anti-inhibitor coagulant complex (human) is readily available in the hospital.

More recently, the Neurocritical Care Society and Society of Critical Care Medicine guidelines for reversal of antithrombotics in intracranial hemorrhage have suggested the use of anti-inhibitor coagulant complex (human) or 4-factor prothrombin complex concentrate (human) for patients with intracranial hemorrhage associated with dabigatran (if idarucizumab is unavailable) or oral direct factor Xa inhibitors (eg, apixaban, edoxaban, or rivaroxaban) if intracranial hemorrhage occurred within 3 to 5 terminal half-lives of drug exposure or if liver failure exists. Anti-inhibitor coagulant complex (human) may also be used in patients with intracranial hemorrhage to reverse the effects of full-therapeutic dose pentasaccharides (fondaparinux).

Life-threatening bleeding associated with non-vitamin K antagonist anticoagulants

Data from a limited number of patients studied (multiple case reports) suggests that anti-inhibitor coagulant complex (human) may be beneficial in the treatment of life-threatening bleeding associated with dabigatran [Dager 2013], [Faust 2014], [Kiraly 2013], [Neyens 2014], [Schulman 2014] or rivaroxaban [Kiraly 2013], [Maurice-Szamburski 2014]. In addition, in vitro and ex vivo data evaluating the effect of anti-inhibitor coagulant complex (human) on various coagulation parameters affected by apixaban, edoxaban, or rivaroxaban suggests that anti-inhibitor coagulant complex (human) may be effective in the reversal of oral direct factor Xa inhibitor mediated anticoagulation [Escolar 2013], [Fukuda 2012], [Halim 2014], [Marlu 2012], [Perzborn 2014]. Additional data may be necessary to further define the role of anti-inhibitor coagulant complex (human) in this setting. Of note, idarucizumab is FDA approved for the reversal of the anticoagulant effects of dabigatran in the event of a life-threatening or uncontrolled bleeding episode.

Based on the Updated European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Anticoagulants in Patients with Non-Valvular Atrial Fibrillation, the use of anti-inhibitor coagulant complex (human) may be considered for the treatment of life-threatening bleeding associated with dabigatran (if idarucizumab is not available) or oral direct factor Xa inhibitors (apixaban, edoxaban, or rivaroxaban) if anti-inhibitor coagulant complex (human) is readily available in the hospital.

There are no dosage adjustments provided in the manufacturer's labeling.

For IV injection or infusion only; maximum infusion rate: 2 units/kg/minute. A syringe pump may be used to control the rate of administration. Use plastic luer lock syringes (anti-inhibitor coagulant complex may stick to the surface of all-glass syringes); do not administer in the same tubing or container with other medications. Following reconstitution, complete infusion within 3 hours.

Frequency not defined.

Cardiovascular: Cerebrovascular accident (embolic/thrombotic stroke), chest discomfort, chest pain, decreased blood pressure, flushing, hypertension, hypotension, myocardial infarction, pulmonary embolism, tachycardia, thromboembolism, thrombosis (arterial thrombosis, venous thrombosis)

Central nervous system: Chills, dizziness, drowsiness, headache, hypoesthesia (including facial), malaise, paresthesia

Dermatologic: Pruritus, skin rash, urticaria

Gastrointestinal: Abdominal distress, diarrhea, dysgeusia, nausea, vomiting

Hematologic & oncologic: Disseminated intravascular coagulation

Hypersensitivity: Angioedema, hypersensitivity reaction (including anaphylaxis)

Immunologic: Antibody development (anamnestic response)

Local: Pain at injection site

Miscellaneous: Fever

Respiratory: Bronchospasm, cough, dyspnea, wheezing