Aminocaproic Acid (Monograph)

Drug class: Hemostatics

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Antifibrinolytic agent; synthetic lysine analog.^{110 111 r123}

Uses for Aminocaproic Acid

Treatment of Bleeding Due to Elevated Fibrinolytic Activity

Used for management of acute bleeding disorders due to elevated fibrinolytic activity.^{110 111} In life-threatening situations, transfusion of appropriate blood products and other emergency measures may be required.^{110 111}

Manufacturers state that aminocaproic acid should be used only after hyperfibrinolysis has been confirmed with a definite diagnosis and/or laboratory studies.^{110 111}

Situations associated with fibrinolytic bleeding in which aminocaproic acid may be used include bleeding associated with heart surgery (with or without cardiac bypass procedures) and portacaval shunt; carcinoma of the lung, prostate, cervix, or stomach; abruptio placentae; hepatic cirrhosis; and hematologic disorders such as amegakaryocytic thrombocytopenia accompanying aplastic anemia (reduces the need for platelet transfusions).^{108 109 110 111 r120 133}

Patients with hepatic cirrhosis may experience bleeding from hyperfibrinolytic activity.^r120 American Gastroenterology Association (AGA) states that antifibrinolytic therapy such as aminocaproic acid may be considered in those with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity.^r120

Also has been used in situations where urinary fibrinolysis contributes to excessive urinary tract fibrinolytic bleeding associated with surgical hematuria such as that following prostatectomy and nephrectomy, or nonsurgical hematuria accompanying polycystic or neoplastic disease of the genitourinary tract.^{110 111}

Hyphema

Has been used orally or topically (applied directly to the eye) for the prevention of secondary ocular hemorrhage in patients with nonperforating traumatic hyphema^{† [off-label]}.^{100 101 102 103 104 105 106 136} Designated an orphan drug by FDA for topical treatment of traumatic hyphema.¹¹⁹

A 2023 Cochrane review found no good evidence to support use of antifibrinolytic agents in traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage.¹³⁶

Prevention of Perioperative Bleeding

Has been used for prophylaxis of postoperative bleeding^{† [off-label]}.¹³³

Antifibrinolytics (aminocaproic acid and tranexamic acid) are commonly used as a blood conservation approach during cardiac surgery and have been shown to reduce bleeding and transfusion rates.^{r123 r124 r125 r126}

Antifibrinolytics also have been used to inhibit fibrinolysis during liver transplantation; however, there is much less evidence with aminocaproic acid than tranexamic acid in this setting.^{131 132}

Prevention of Bleeding During Dental Procedures

Antifibrinolytic agents such as aminocaproic acid are commonly used to prevent excessive bleeding following minor oral surgery and dental extractions in patients with inherited bleeding disorders (e.g., hemophilia, von Willebrand disease)^{† [off-label]}.^r128

The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation recommends the use of antifibrinolytic agents (e.g., aminocaproic acid, tranexamic acid) as adjunctive treatment of mouth or other mucosal bleeding in patients with hemophilia or von Willebrand disease.^{129 130}

Hereditary Angioedema

Antifibrinolytics such as aminocaproic acid have been used for long-term prophylaxis in patients with hereditary angioedema (HAE)^{† [off-label]} due to a deficiency of complement 1 (C1)-esterase inhibitor.¹³⁵ Considered second-line therapy for this use.¹³⁵

Hereditary Hemorrhagic Telangiectasia

Has been used orally for the management of hereditary hemorrhagic telangiectasia^{† [off-label]}.^{112 113 134} However, oral tranexamic acid is recommended in current expert guidelines for the management of epistaxis in patients with hereditary hemorrhagic telangiectasia.¹³⁴

Aminocaproic Acid Dosage and Administration

General

Pretreatment Screening

• Perform appropriate testing to determine the amount of fibrinolysis present.^{110 111}

Patient Monitoring

• Monitor creatine kinase (CK, creatine phosphokinase, CPK) levels in patients on long-term therapy.^{110 111}

Administration

Administer orally or by IV infusion.^{110 111}

Oral Administration

Administer orally (as tablets or oral solution) if the patient is able to take oral medication.¹¹⁰

IV Administration

Administer by IV infusion after dilution.¹¹¹

Avoid rapid IV administration; hypotension, bradycardia, and/or arrhythmia may result.¹¹¹

Dilution

For the initial infusion to be administered during the first hour of treatment, manufacturer suggests that 4–5 g of aminocaproic acid (16–20 mL of the injection concentrate) be added to 250 mL of diluent.¹¹¹

For maintenance infusions, add 1 g of aminocaproic acid (4 mL of the injection concentrate) to 50 mL of diluent.¹¹¹

Compatible with the following solutions: sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, and Ringer's injection.¹¹¹ Although the injection is compatible with sterile water for injection, resultant solutions are hypo-osmolar.¹¹¹

Standardize for Safety

Standardized concentrations for IV aminocaproic acid have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.²⁴⁹ Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.²⁴⁹ For additional information on S4S, see [Web].

Dosage

Pediatric Patients

Bleeding Due to Elevated Fibrinolytic Activity

Oral or IV

Although safety and efficacy in children not established,^{110 111} the drug has been used as a hemostatic agent in pediatric patients^† at an IV or oral loading dose of 100–200 mg/kg, followed by a maintenance dosage of 100 mg/kg per dose every 4 to 6 hours (maximum dose of 30 g/24 hour).¹³⁸ .

Hereditary Angioedema

Oral

In pediatric patients requiring long-term prophylaxis for hereditary angioedema^†, aminocaproic acid has been administered at a dosage of 0.05 g/kg orally twice a day (with dosage ranging from 0.025 g/kg twice a day to 0.1 g/kg twice a day).¹³⁵

Adults

Bleeding Due to Elevated Fibrinolytic Activity

Oral

5 g (as tablets or oral solution) during the first hour, then 1 g (as oral tablets) or 1.25 g (as oral solution) per hour for about 8 hours or until bleeding has been controlled.¹¹⁰

IV

Initial infusion (loading dose): 4–5 g over 1 hour.¹¹¹

Maintenance infusion: 1 g per hour for about 8 hours or until bleeding has been controlled.¹¹¹

Hyphema†

Oral

100 mg/kg (up to 5 g) every 4 hours, up to a maximum daily dosage of 30 g, for 5 days has been used;^{100 101 102 103} lower daily dosages also may be effective.¹⁰²

Prevention of Perioperative Bleeding

IV

For prevention of bleeding during cardiac surgery^†, aminocaproic acid has been administered IV as a loading dose of 1–15 g at induction of anesthesia, followed by a maintenance dosage of 1–2 g/hour during surgery.^r126 In another study in patients undergoing cardiac surgery, aminocaproic acid was administered as a bolus loading dose of 150 mg/kg followed by a maintenance infusion of 15 mg/kg/hour.^r123 The drug was administered following anesthetic induction.^r123

Prevention of Bleeding During Dental Procedures

Oral or IV

For the treatment of mouth or other mucosal bleeds in individuals with hemophilia or von Willebrand disease^†, an oral aminocaproic acid dose of 50 to 100 mg/kg has been administered.^{129 130} A dose of factor concentrate must be administered first to form the clot, followed by aminocaproic acid given every 6 hours to preserve the clot until healing occurs in about 10 to 14 days.^{129 130} Aminocaproic acid also may be administered IV following dental (e.g., wisdom tooth extraction) or ENT (e.g., tonsillectomy) surgery.^{129 130}

Hereditary Angioedema

Oral

For long-term prophylaxis in adults with hereditary angioedema^†, aminocaproic acid has been administered at a dosage of 2 g orally 3 times a day (with dosage ranging from 1 g twice a day to 4 g 3 times a day).¹³⁵

Hereditary Hemorrhagic Telangiectasia†

Oral

1 or 1.5 g twice daily for 1–2 months, followed by 1–2 g daily has been used.¹¹²

Cautions for Aminocaproic Acid

Contraindications

• Active intravascular clotting process.^{110 111}

• When it is not clear whether hemorrhage is secondary to primary fibrinolysis or disseminated intravascular coagulation (DIC), the distinction must be made before aminocaproic acid is administered.^{110 111} Do not use without concomitant heparin therapy in patients with evidence of DIC.^{110 111}

Warnings/Precautions

Urinary Tract Bleeding

Intrarenal obstruction via glomerular capillary thrombosis or clots in the renal pelvis and ureters reported in patients with upper urinary tract bleeding who received aminocaproic acid.^{110 111} Do not use in patients with hematuria of upper urinary tract origin unless the potential benefits outweigh risks.^{110 111}

Musculoskeletal Effects

Skeletal muscle weakness with necrosis of muscle fiber reported with prolonged administration.^{110 111} Presentation may range from mild myalgias with weakness and fatigue to severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure; CK levels are elevated.^{110 111} Manifestations resolve with drug discontinuance but may recur if therapy is reinstated.^{110 111}

Monitor CK concentrations with long-term therapy.^{110 111} Discontinue drug if an increase in CK occurs.^{110 111}

If skeletal myopathy occurs, consider possibility of cardiac muscle damage.^{110 111}

Benzyl Alcohol in Neonates

Aminocaproic acid injection contains benzyl alcohol, which has been associated with toxicity (fatalities) in neonates.^{110 111} (See Pediatric Use under Cautions.)

Hyperfibrinolysis

Should be used only in acute, life-threatening situations involving hemorrhage resulting from hyperfibrinolysis that has been confirmed by laboratory studies.^{110 111}

Clot Formation

Inhibition of fibrinolysis by aminocaproic acid may theoretically result in clotting or thrombosis; however, there is no definite evidence that the drug is responsible for cases of intravascular clotting that have occurred following administration.^{110 111}

CNS Effects

Neurologic deficits (hydrocephalus, cerebral ischemia, cerebral vasospasm) associated with use of antifibrinolytic agents in the management of subarachnoid hemorrhage.^{110 111} Causal relationship to the drugs not established.^{110 111}

Specific Populations

Pregnancy

Animal reproduction studies have not been conducted with aminocaproic acid.^{110 111} It is not known whether aminocaproic acid can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.^{110 111} Aminocaproic acid should be given to a pregnant woman only if clearly needed.^{110 111}

Lactation

Not known if aminocaproic acid is distributed into human milk; caution if used in nursing women.^{110 111}

Pediatric Use

Safety and efficacy not established.^{110 111}

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (fatal “gasping syndrome”) in neonates; each mL of aminocaproic acid injection in multiple-dose vials contains 9 mg of benzyl alcohol.^{114 115 116 117 118}

American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.¹¹⁴

Common Adverse Effects

Adverse effects have included nausea, vomiting, cramping, abdominal pain, diarrhea, dizziness, malaise, dyspnea, nasal congestion, headache, edema, pruritus.^{110 111}

Drug Interactions

Specific Drugs

Aminocaproic Acid Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed from the GI tract; peak plasma concentrations are attained within about 1 hour following a 5-g oral dose.¹¹¹

Special Populations

Plasma concentrations may be higher in patients with severe renal impairment.^{110 111}

Distribution

Extent

After prolonged administration, distributed through extravascular as well as intravascular compartments; penetrates human red blood cells and other body cells.^{110 111}

Not known if aminocaproic acid is distributed into human milk.^{110 111}

Elimination

Metabolism

The major portion of aminocaproic acid is not metabolized.¹¹¹

Elimination Route

Eliminated principally in urine as unchanged drug (65%) and the adipic acid metabolite (11%).¹¹¹

Half-life

Approximately 2 hours.^{110 111}

Special Populations

Removed by hemodialysis; may be removed by peritoneal dialysis.¹¹¹

Stability

Storage

Oral

Tablets

20–25°C; tight, child-resistant containers.¹¹⁰ Do not freeze.¹¹⁰

Oral Solution

20–25°C; tight, child-resistant containers.¹¹⁰ Do not freeze.¹¹⁰

Parenteral

Injection

20–25°C (excursions permitted to 15–30°C).¹¹¹

Actions

• Synthetic lysine derivative; inhibitor of fibrinolysis.^{110 111}

• Inhibits the activation of plasminogen; also inhibits the action of plasmin.^{110 111} Inhibits binding of plasmin to fibrin by occupying lysine-binding sites of plasminogen.^{110 111}

Advice to Patients

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.^{110 111}

• Advise patients to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.^{110 111}

• Inform patients of other important precautionary information.^{110 111}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Related/similar drugs

Medical Disclaimer