PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Synthetic Antifibrinolytics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral inhibitor of fibrinolysis
    Used for enhancing hemostasis when fibrinolysis contributes to bleeding
    Associated with potential risk for clotting or thrombosis.

    COMMON BRAND NAMES

    Amicar

    HOW SUPPLIED

    Amicar/Aminocaproic Acid Intravenous Inj Sol: 1mL, 250mg
    Amicar/Aminocaproic Acid Oral Sol: 0.25g, 1mL
    Amicar/Aminocaproic Acid Oral Tab: 500mg, 1000mg

    DOSAGE & INDICATIONS

    For the treatment of hemorrhage caused by hyperfibrinolysis.
    Oral dosage
    Adults

    5 g PO the first hour, followed by 1 to 1.25 g/hour PO for 8 hours or until bleeding is controlled. Max: 30 g/day.

    Children† and Adolescents†

    100 to 200 mg/kg/dose PO once, followed by 100 mg/kg/dose PO every 6 hours. Max: 30 g/day.

    Intravenous dosage
    Adults

    4 to 5 g IV over 1 hour, followed by 1 g/hour continuous IV infusion for 8 hours or until bleeding is controlled. Max: 30 g/day.[50659]

    Children† and Adolescents†

    100 to 200 mg/kg IV, followed by 100 mg/kg IV every 6 hours. Max: 30 g/day. Alternatively, 100 mg/kg or 3 g/m2 IV, followed by 33.3 mg/kg/hour or 1 g/m2/hour continuous IV infusion, not to exceed 18 g/m2/day.

    For dental bleeding† in patients with hemophilia A.
    For prevention of dental bleeding† after dental surgery.
    Oral dosage
    Adults

    6 g PO immediately after surgery, then 6 g PO every 6 hours for 9 to 10 days. Max: 30 g/day.

    For treatment of dental bleeding† after dental extraction.
    Topical dosage (parenteral solution)
    Adults

    Soak small piece of oxidized cellulose in approximately 2 molar solution and pack tooth socket.[24534]

    For control of acute gingival bleeding† unrelated to dental extraction.
    Topical dosage (oral solution)
    Adults

    1.25 g PO as oral rinse for 30 seconds after initial rinses with hydrogen peroxide followed by saline. Repeat every 4 hours until bleeding is controlled.[24535]

    Children and Adolescents

    May apply with a cotton swab.

    For intracranial rebleeding prophylaxis after recent aneurysmal subarachnoid hemorrhage†.
    Intravenous dosage
    Adults

    4 or 5 g IV followed by 1 g/hour continuous IV infusion for up to 72 hours with treatment discontinued 4 to 6 hours before angiography when possible.[58114] [58115] [58116] Guidelines recommend short-term (less than 72 hours) therapy to reduce the risk of early aneurysm rebleeding for patients with unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications.[58117]

    For the treatment of hemorrhagic cystitis† induced by cyclophosphamide therapy, radiation therapy, or interstitial cystitis.
    Intravesical dosage
    Adults

    20 mg/100 mL continuous bladder irrigation until 24 hours after the urine becomes clear.[24536]

    For the prevention of secondary ocular hemorrhage in patients with traumatic hyphema†.
    NOTE: Topical aminocaproic acid has been designated an orphan drug by the FDA for this indication.
    Oral dosage
    Adults

    100 mg/kg/dose PO (Max: 5 g/dose) every 4 hours for 5 days. Max: 30 g/day.[24959]

    Children and Adolescents

    100 mg/kg/dose PO every 4 hours for 5 days. Max: 30 g/day.[24960] Relative efficacy compared with placebo has not been studied in a high-risk pediatric population.

    For angioedema prophylaxis† in patients with hereditary angioedema.
    Oral dosage
    Adults

    16 g/day PO in divided doses every 4 or 6 hours for up to a month then 2 to 12 g/day PO in 2 to 4 divided doses. Usual dose: 2 g PO 3 times daily (range, 1 g PO twice daily to 4 g PO 3 times daily).

    For surgical bleeding prophylaxis† in cardiopulmonary bypass as monotherapy or in combination with desmopressin (DDAVP).
    Intravenous dosage
    Adults

    5 g IV before skin incision, followed by 1 g/hr continuous IV infusion for 6 to 8 hours. In combination with DDAVP, 5 g IV once preoperatively.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    30 g/day IV or PO; 36 g/day IV or PO has been used off-label in subarachnoid hemorrhage.

    Elderly

    30 g/day IV or PO; 36 g/day IV or PO has been used off-label in subarachnoid hemorrhage.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; dosage should be modified depending on clinical response and degree of renal impairment.

    ADMINISTRATION

    Oral Administration
    Oral Liquid Formulations

    Oral solution: Administer using a calibrated measuring device.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Use of an infusion pump is recommended to ensure accurate dosing.
    Rapid injection of undiluted drug is NOT recommended. Rapid administration may result in hypotension, bradycardia, and/or arrhythmia.[50659]
    Intermittent IV Infusion
    Dilute the initial dose (4 to 5 g of aminocaproic acid) in 250 mL of 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection. Although Sterile Water for Injection is compatible, the resultant solution is hypoosmolar.
    Administer IV over 1 hour.[50659]
    Continuous IV Infusion
    After the initial dose, infuse at a rate of 1 g/hour in 50 mL of diluent. This method of treatment is usually continued for 8 hours or until bleeding is controlled.[50659]

    Topical Administration

    NOTE: Aminocaproic acid is not FDA-approved for topical administration.
    Pressure packs: Use gauze pressure packs containing aminocaproic acid, or a small piece of oxidized cellulose soaked in approximately 2 molar aminocaproic acid (prepared from the 250 mg/mL parenteral product).
    Oral rinse: Rinse with hydrogen peroxide, followed by saline, then rinse with 1.25 g aminocaproic acid oral solution for 30 seconds.
    Cotton swabs: For use in unconscious patients or children, apply oral solution with a cotton swab.

    Other Administration Route(s)

    Intravesical Administration
    NOTE: Aminocaproic Acid is not FDA-approved for intravesical administration.
    Administer via a 22F or 24F three-way Foley catheter inserted into the bladder.
    Irrigate the bladder with 0.9% Sodium Chloride to remove all clots.
    Irrigate bladder continuously with a solution containing 200 mg of aminocaproic acid added to each liter of 0.9% Sodium Chloride, starting in the recovery room at a rate adjusted according to the severity of bleeding. Adjust the rate of irrigation as urine clears, and continue for 24 hours after urine becomes clear.

    STORAGE

    Amicar:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Disseminated intravascular coagulation (DIC)

    Aminocaproic acid is contraindicated in patients with an active intravascular clotting process or disseminated intravascular coagulation (DIC) without concomitant heparin. Distinguish whether bleeding is a result of primary fibrinolysis or DIC before aminocaproic acid initiation. In DIC, the platelet count is usually decreased, protamine paracoagulation test is positive, and the euglobulin clot lysis test is normal. Do not administer aminocaproic acid without a definitive diagnosis and/or laboratory finding indicative of hyperfibrinolysis (hyperplasminemia). Inhibition of fibrinolysis by aminocaproic acid may theoretically result in clotting or thrombosis. However, there is no direct evidence that aminocaproic acid use has been responsible for the few reported cases of intravascular clotting after treatment. Rather, it appears that such intravascular clotting was most likely attributable to the patient's preexisting clinical condition (e.g., DIC).[28471] [50659]

    Hematuria

    Do not use aminocaproic acid in hematuria of upper urinary tract origin, unless the potential benefits outweigh the risk. Aminocaproic acid use in patients with upper urinary tract bleeding has been known to cause intrarenal obstruction in the form of glomerular capillary thrombosis or clots in the renal pelvis and ureters.[28471] [50659]

    Laboratory test interference

    Aminocaproic acid use may cause laboratory test interference. Prolongation of the template bleeding time has been reported during aminocaproic acid continuous intravenous infusion at dosages exceeding 24 g/day. Platelet function studies in these patients have not demonstrated any platelet dysfunction. However, in vitro studies have shown that at high concentrations (7.4 mMol/L or 0.97 mg/mL or more), aminocaproic acid inhibits ADP and collagen-induced platelet aggregation, serotonin and ATP release, and the binding of fibrinogen to the platelets in a concentration-response manner. Concentrations achieved in vivo clinically in patients with normal renal function are considerably lower than the in vitro concentrations found to induce abnormalities in platelet function tests.[28471] [50659]

    Pregnancy

    Use aminocaproic acid during pregnancy only if clearly needed. It is not known whether aminocaproic acid can cause fetal harm when administered during human pregnancy or if it affects reproduction capacity. Animal reproduction studies with aminocaproic acid have not been conducted.[28471] [50659]

    Breast-feeding

    It is not known if aminocaproic acid is excreted into breast milk. Because many drugs are excreted into breast milk, use aminocaproic acid with caution in a breast-feeding woman.[28471] [50659]

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    stroke / Early / Incidence not known
    seizures / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    myoglobinuria / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    skin necrosis / Early / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    hypotension / Rapid / Incidence not known
    hallucinations / Early / Incidence not known
    delirium / Early / Incidence not known
    confusion / Early / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    edema / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known

    Mild

    syncope / Early / Incidence not known
    dizziness / Early / Incidence not known
    headache / Early / Incidence not known
    fatigue / Early / Incidence not known
    weakness / Early / Incidence not known
    myalgia / Early / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    vomiting / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    malaise / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known

    DRUG INTERACTIONS

    Anti-inhibitor Coagulant Complex: (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.
    Factor IX: (Major) In general, aminocaproic acid should not be administered simultaneously with factor IX complex, factor IX concentrates, factor IX Fc fusion protein, recombinant, and factor IX albumin fusion protein, recombinant due to the increased risk of thrombosis. Some hematologists recommend separating administration of aminocaproic acid from these clotting factor complexes by 8 hours. Aminocaproic acid has been used concurrently with human factor IX complexes or anti-inhibitor coagulant complex perioperatively in hemophiliac patients. The risk of developing thrombosis, however, is increased. In rare instances, thrombosis leading to acute myocardial infarction or gangrene has been reported in patients with hemophilia receiving combination therapy with factor IX concentrate and aminocaproic acid. Concomitant administration of aminocaproic acid with purer formulations of factor IX may also result in an increased risk of thrombosis.
    Prothrombin Complex Concentrate, Human: (Major) In general, aminocaproic acid should not be administered simultaneously with factor IX complex, factor IX concentrates, factor IX Fc fusion protein, recombinant, and factor IX albumin fusion protein, recombinant due to the increased risk of thrombosis. Some hematologists recommend separating administration of aminocaproic acid from these clotting factor complexes by 8 hours. Aminocaproic acid has been used concurrently with human factor IX complexes or anti-inhibitor coagulant complex perioperatively in hemophiliac patients. The risk of developing thrombosis, however, is increased. In rare instances, thrombosis leading to acute myocardial infarction or gangrene has been reported in patients with hemophilia receiving combination therapy with factor IX concentrate and aminocaproic acid. Concomitant administration of aminocaproic acid with purer formulations of factor IX may also result in an increased risk of thrombosis.
    Thrombolytic Agents: (Severe) The actions of aminocaproic acid can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Tretinoin, ATRA: (Major) Rare cases of fatal thrombotic complications have been reported in patients treated with systemic tretinoin, and antifibrinolytic agents. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin, ATRA therapy. Monitor patients closely and avoid if possible.

    PREGNANCY AND LACTATION

    Pregnancy

    Use aminocaproic acid during pregnancy only if clearly needed. It is not known whether aminocaproic acid can cause fetal harm when administered during human pregnancy or if it affects reproduction capacity. Animal reproduction studies with aminocaproic acid have not been conducted.[28471] [50659]

    It is not known if aminocaproic acid is excreted into breast milk. Because many drugs are excreted into breast milk, use aminocaproic acid with caution in a breast-feeding woman.[28471] [50659]

    MECHANISM OF ACTION

    Aminocaproic acid inhibits both the activity of plasminogen activators and to a lesser degree, plasmin activity by binding to lysine-binding sites within the plasminogen/plasmin molecule, which interferes with the ability of plasmin to lyse fibrin clots. Low concentrations of epsilon-aminocaproic acid (EACA) inhibit in vitro profibrinolysin activation by streptokinase and urokinase. Aminocaproic acid may suppress chymotrypsin proteolytic enzymes and antigen-antibody reactions. Aminocaproic acid does not alter the concentrations of clotting factors. EACA diminishes the tuberculin reaction in patients sensitive to tuberculin. The antihistaminic action of this agent is not clinically significant.

    PHARMACOKINETICS

    Aminocaproic acid is administered orally and intravenously. Apparent Vd is estimated to be 23.1 L after oral administration and 30 L after intravenous administration. With prolonged administration, aminocaproic acid distributes throughout extravascular and intravascular compartments, penetrating red blood cells and other tissue cells. Renal excretion is the primary route of elimination; 65% of the dose is recovered in the urine unchanged, and 11% appears as the metabolite adipic acid. Renal clearance (116 mL/minute) approximated endogenous creatinine clearance. Total body clearance is 169 mL/minute. Terminal elimination half-life is approximately 2 hours.[28471] [50659]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Oral Route

    Oral absorption appears to be a zero-order process with an absorption rate of 5.2 g/hour. Mean lag time in absorption is 10 minutes. After a single oral dose of 5 g, absorption was complete. Mean peak plasma concentrations (164 mcg/mL) were attained 1.2 hours.[28471]