Aminocaproic acid - Dosage, side effects, MOA ...

Aminocaproic acid prevents fibrinolysis by inhibiting the conversion of plasminogen into plasmin. It is used to secure hemostasis in the following conditions:

  • Patients with uncontrolled bleeding following surgical procedures especially cardiac surgery
  • Hematologic disorders like patients with hemophilia
  • Neoplastic disorders
  • Abruptio placentae,
  • Hepatic cirrhosis, and
  • Urinary fibrinolysis

It may also be used (off-label) in the following conditions:

  • Patients who are on anticoagulants and bleeding due to dental procedures
  • Uncontrolled bleeding due to severe thrombocytopenia
  • Refractory bleeding associated with extracorporeal membrane oxygenation
  • Thrombolytic associated intracranial hemorrhage

Adult dose :

  • Aminocaproic acid dose in acute bleeding:
    • A Loading dose of 4 to 5 gms oral or intravenous during the first hour, followed by a maintenance dose of 1 gm/hour for 8 hours (or 1.25 g/hour of oral solution) or until bleeding is controlled. The maximum recommended daily dose is 30 gms.
  • Aminocaproic acid dose in bleeding patients with severe thrombocytopenia
    • 100 mg/kg intravenously over 30 to 60 minutes to a maximum of 5 gms. This is followed by 1 to 4 gms oral or intravenous infusion every 4 to 8 hours or 1 g/hour to a maximum daily dose of 24 gms.
  • Aminocaproic acid dose in patients with uncontrolled bleeding and a congenital or acquired coagulation disorder.
    • 50 to 60 mg/kg every 4 hours.
  • Patients with refractory bleeding associated with extracorporeal membrane oxygenation:
    • 4 to 5 g intravenous loading dose followed by an infusion rate of 1 to 1.25 g/hour until bleeding is controlled.
  • Patients with iatrogenic Intracranial hemorrhage associated with thrombolytics (plasminogen-activator, alteplase, reteplase, tenecteplase)
    • 4 to 5 g intravenous as an alternative to cryoprecipitate. The fibrinogen levels should be measured after administration. Cryoprecipitate should be given if the fibrinogen levels are less than 150 mg/dL.
  • For the prevention of dental procedure bleeding in patients on anticoagulant therapy:
    • Oral rinse: Hold 4 g/10 mL of the solution in mouth for 2 minutes and then spit out. Repeat 6 hourly for 2 days after the procedure.
  • For the Prevention of perioperative bleeding associated with cardiac surgery:
    • A Loading dose of 75 to 150 mg/kg intravenous, followed by 10 to 15 mg/kg/hour intravenous infusion Or
    • A Loading dose of 10 gms followed by 2 g/hour during surgery or
    • 10 gms over 20 to 30 minutes prior to the incision, followed by 10 gms after heparin administration and then 10 gms at discontinuation of cardiopulmonary bypass.
  • Subarachnoid hemorrhage:
    • A Loading dose of 4 gms intravenous followed by 1 gm/hour infusion for up to 72 hours after the onset of subarachnoid hemorrhage.

Dose in children :

  • Control of bleeding in hemophilic patients:
    • 50-100 mg/kg/dose four times a day to a maximum of 24 gms per day.
  • Control of bleeding in patients with a platelets disorder:
    • 50-100 mg/kg/dose four times a day orally or intravenous to a maximum of 24 gms/day.
  • Refractory gross hematuria:
    • 100 mg/kg/dose four times a day for 2 days beyond the resolution of hematuria in children aged 11 years or more.
  • Prevention of bleeding in hemophilia patients (associated with dental procedures):
    • 50-100 mg/kg/dose orally four times a day orally to a maximum daily dose of 24 gm/day in combination with desmopressin or factor VIII replacement therapy until healing is complete or for up to 7 days.
  • For prevention of bleeding in high-risk patients associated with extracorporeal membrane oxygenation (ECMO):
    • 100 mg/kg intravenously prior to cannulation followed by 25-30 mg/kg/hour for up to 72 hours. The target activated clotting time (ACT) during aminocaproic acid therapy should range between 180-200 seconds.

 

Pregnancy Risk Factor C

Aminocaproic acids have not been used in pregnancy. Aminocaproic acid use during breastfeeding: It is unknown if the drug can be absorbed into breastmilk. It should not be used by nursing women.  

Renal dose :

Aminocaproic acid may accumulate in patients with impaired renal functions. A reduced loading dose followed by a maintenance continuous infusion rate of 5 mg/kg/hour may be reasonable. Gravlee, 2008.

Dose in liver disease :

 The manufacturer does not recommend any dose adjustment in liver disease.

 

Side effects of Aminocaproic acid:

  • Cardiovascular:
    • Arrhythmias, bradycardia, edema, low blood pressure, raised intracranial pressure, syncope, and thrombosis
  • Central nervous system:
    • Confusion, delirium, dizziness, lethargy, hallucinations, headache, seizures, and stroke.
  • Dermatologic:
    • Rash and pruritus
  • Gastrointestinal:
    • Abdominal pain & cramps, diarrhea, nausea, and vomiting
  • Genitourinary:
    • Dry ejaculation
  • Hematologic:
    • Agranulocytosis, leukopenia, and thrombocytopenia.
  • Local:
    • Injection site pain & necrosis
  • Neuromuscular & skeletal:
    • Myalgia, myositis, and  rhabdomyolysis
  • Ophthalmic:
    • Watery eyes and reduced vision.
  • Otic:
    • Tinnitus
  • Renal:
    • Increased BUN, myoglobinuria, and acute renal failure.
  • Respiratory:
    • Shortness of breath, nasal congestion, and pulmonary embolism.
  • Miscellaneous:
    • Allergic reactions and anaphylaxis
  • Rare case reports include myocardial infarction and hyperkalemia

 

Contraindications to aminocaproic acid include:

  • DIAC (Disseminated intravascular Cocoagulation)
  • Active intravascular thrombosis

Warnings and Precautions

  • Occlusion of the intrarenal:
    • There may be clot formation and glossular capillarythrombosis. Aminocaproic acid should not be recommended for patients with hematurias of the upper urinary tract.
  • Skeletal muscle weakness
    • It has been associated with myalgias and fatigue as well as myopathy in severe cases. If CPK levels rise after therapy is initiated, it should be stopped.
    • Do not use factor IX concentrates.
    • Patients with severe renal impairment should be cautious.

   

Aminocaproic acid: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use
    •  

    Risk Factor C (Monitor therapy).

    Tretinoin (Systemic) Antifibrinolytic agents may have a greater thrombogenic effect.

    Risk Factor X (Avoid Combination)

     
    Complex Anti-inhibitor Coagulant (Human). Antifibrinolytic agents may increase the thrombogenic effects of Anti-inhibitor Coagulant Complex Human.
    Factor IX Complex (Human). [(Factors II. IX. X)] Aminocaproic acid may increase the toxic/adverse effect of Factor IX Complex Human [(Factors II. IX. X). This combination could increase your risk of developing thrombosis.

Monitoring parameters :

 Monitor fibrinogen, fibrin split products, creatine phosphokinase with long-term therapy, BUN, and creatinine.

How to adminnister :

Aminocaproic acid should be given as a slow intravenous infusion over 15 - 60 minutes to avoid hypotension, bradycardia, and arrhythmia. The oral formulation may be taken without regard to meals.

Pharmacology & MOA :

Aminocaproic acids binds competitively with plasminogen and blocks its binding to fibrin. It inhibits the conversion from plasminogen into plasmin, and also inhibits fibrin degradation which forms a meshwork near the site of bleeding.

  • The Onset of action varies from 1 to 72 hours
  • It is minimally metabolized by the liver.
  • Oral bioavailability is close to 100%
  • Half-life elimination is around 2 hours
  • The time to peak plasma concentration is around one hour.
  • Excretion is mainly via urine.

International brands :

  • Acepramin
  • Acidum e-aminocapronicum
  • AKK
  • Amicar
  • Caproamin
  • Caprolest
  • Caprolex
  • Caprolisin
  • EAC
  • Epsamon
  • Epsicaprom
  • Epsikapron
  • Epsilon
  • Hamostat
  • Hexalense
  • Inselon
  • Ipron
  • Ipsilon
  • Kai Nai Yin
  • Minocap
  • Plaslloid
  • Resplamin
  • Syrop acidi e-aminocapronici

Brands in pakistan :

 No brands available in Pakistan.

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