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.