AHFS Class:

• Hemostatics 20:28.16

Generic Name(s):

• Aminocaproic Acid

Aminocaproic acid, a synthetic lysine analog, is an antifibrinolytic agent.110,111,120,123

Treatment of Bleeding Due to Elevated Fibrinolytic Activity

Aminocaproic acid is used for the management of acute bleeding disorders due to elevated fibrinolytic activity.110,111 The manufacturers state that the drug should be used only after hyperfibrinolysis has been confirmed with a definite diagnosis and/or laboratory studies.110,111 In life-threatening situations, transfusion of appropriate blood products and other emergency measures may be required.110,111

Situations associated with fibrinolytic bleeding in which aminocaproic acid may be useful include bleeding associated with surgical complications following heart surgery (with or without cardiac bypass procedures) and portacaval shunt; neoplastic diseases such as carcinoma of the lung, prostate, cervix, or stomach; acute and life-threatening abruptio placentae; hepatic cirrhosis; and hematologic disorders such as amegakaryocytic thrombocytopenia (accompanying aplastic anemia).108,109,110,111,120,133

Patients with hepatic cirrhosis may experience bleeding from hyperfibrinolytic activity.120 The 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.120

Aminocaproic acid 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

Aminocaproic acid has been used orally and topically (direct application to the eye) for the prevention of secondary ocular hemorrhage in patients with nonperforating traumatic hyphema†.100,101,102,103,104,105,106,136 Aminocaproic acid is designated an orphan drug by FDA for topical treatment of traumatic hyphema.119 In placebo-controlled studies, preventive therapy with systemically administered drug was associated with a secondary hemorrhage (rebleeding) rate of 0-5% versus 23-33% for placebo.100,101,102,103,106 A Cochrane review published in 2023 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

Aminocaproic acid has been used for prophylaxis of postoperative bleeding†; results of randomized placebo-controlled trials indicate that administration of the drug before and/or during a procedure is effective in reducing total perioperative blood loss and transfusion requirements in major cardiac, orthopedic, or liver surgery.126,133

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.123,124,125,126,127 In a randomized double-blind study that compared tranexamic acid and aminocaproic acid in patients undergoing cardiac surgery with cardiopulmonary bypass, there was no difference in chest tube drainage (blood loss) between the treatment groups; however, fewer patients who received aminocaproic acid required a blood transfusion in the first 24 hours following surgery compared with patients who received tranexamic acid.123

Aminocaproic acid also has been used to inhibit fibrinolysis during liver transplantation; however, there is much less evidence with aminocaproic acid than tranexamic acid in this setting.132 In one study, aminocaproic acid effectively controlled fibrinolysis and oozing during hepatic allotransplantation in patients with evidence of severe fibrinolysis during reperfusion of the liver and in vitro evidence of aminocaproic acid-improved coagulation (determined by thrombelastography).109 Results of a prospective randomized study in 132 patients undergoing liver transplantation found that tranexamic acid but not aminocaproic acid significantly reduced total red blood cell requirements.131,132 Additional studies are needed to evaluate the effects of aminocaproic acid in patients undergoing liver transplantation.132 132

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)†.128 Clotting factor replacement therapy is commonly given during and after surgery to prevent bleeding complications in these patients.128 Given their low cost, high tolerability, and evidence of effectiveness and safety, antifibrinolytic agents may be used as alternatives to clotting factor concentrates.128 Efficacy of antifibrinolytic agents was demonstrated in 2 small randomized controlled studies in patients with hemophilia undergoing dental extractions; in these studies, patients who received an antifibrinolytic agent had a reduction in number of bleeding events, amount of blood loss, and need for therapeutic clotting factor concentrates compared with those who received placebo.128 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)† due to a deficiency of complement 1 (C1)-esterase inhibitor.135 Antifibrinolytic agents are considered second-line therapies for long-term prophylaxis of HAE because they are less effective than other drugs recommended for first-line treatment (e.g., C1-esterase inhibitor preparations, lanadelumab).135

Hereditary Hemorrhagic Telangiectasia

Aminocaproic acid has been used orally for the management of hereditary hemorrhagic telangiectasia† in a few adults who had histories of recurrent epistaxis (3-7 times weekly) and/or GI bleeding with moderate anemia.112,113 Use of aminocaproic acid in these adults effectively eliminated or reduced the frequency of bleeding episodes to no more than one episode every 2-3 weeks.112 However, oral tranexamic acid is recommended in current expert guidelines for the management of epistaxis in patients with hereditary hemorrhagic telangiectasia.134

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

Aminocaproic acid is administered orally or by IV infusion (after dilution).110,111 Rapid IV injection of the drug is not recommended since hypotension, bradycardia, and/or arrhythmia may result.111

Oral Administration

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

IV Administration

Aminocaproic acid is administered by IV infusion after dilution.111

Aminocaproic acid injection and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.111

Dilution

For the initial IV infusion to be administered during the first hour of treatment, the manufacturer suggests adding 4-5 g of aminocaproic acid (16-20 mL of the injection concentrate) 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 Aminocaproic acid is 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 4 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. 249Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249Because 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 (including updates that may be available), see [Web].

Dosage

Treatment of Bleeding Due to Elevated Fibrinolytic Activity

Oral therapy: The recommended oral dosage of aminocaproic acid for the treatment of acute bleeding syndromes due to elevated fibrinolytic activity in adults is 5 g (as oral tablets or oral solution) administered during the first hour of treatment, followed by 1 g (as oral tablets) or 1.25 g (as oral solution) per hour for about 8 hours or until bleeding is controlled.110

IV therapy: The recommended IV dosage of aminocaproic acid for the treatment of acute bleeding syndromes due to elevated fibrinolytic activity in adults is 4-5 g by IV infusion during the first hour of treatment, followed by continuous infusion at the rate of 1 g/hour.111 Treatment should generally be continued for about 8 hours or until the hemorrhagic condition is under control.111

Although safety and efficacy of aminocaproic acid in children have not been 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

Hyphema

For prevention of secondary ocular hemorrhage in patients with traumatic hyphema†, an oral aminocaproic acid dosage of 100 mg/kg (up to 5 g per dose) every 4 hours daily, up to a maximum daily dosage of 30 g, for 5 days generally has been used,100,101,102,103 although there is some evidence that lower daily dosages may also be effective.102

Prevention of Perioperative Bleeding

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.126 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 IV infusion of 15 mg/kg/hour.123 The drug was administered following anesthetic induction.123

Prevention of Bleeding During Dental Procedures

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

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

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

Hereditary Hemorrhagic Telangiectasia

When used in the treatment of hereditary hemorrhagic telangiectasia†, aminocaproic acid has been given orally in a dosage of 1 or 1.5 g twice daily for 1-2 months, followed by dosage of 1-2 g daily.112

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 have been reported in patients with upper urinary tract bleeding who received aminocaproic acid.110,111 Do not use aminocaproic acid 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 has been reported with prolonged administration of aminocaproic acid.110,111 The presentation may range from mild myalgias with weakness and fatigue to severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure; in addition, creatine kinase (CK) levels are elevated.110,111 Manifestations usually resolve with drug discontinuance but may recur if therapy is reinstated.110,111 Monitor CK concentrations with long-term aminocaproic acid therapy and discontinue therapy if increased CK concentrations occur.110,111 If skeletal myopathy occurs, consider possibility of cardiac muscle damage.110,111

Benzyl Alcohol in Neonates

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

Hyperfibrinolysis

Aminocaproic acid 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) have been associated with use of antifibrinolytic agents in the management of subarachnoid hemorrha however, a causal relationship has not been 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

It is not known whether aminocaproic acid is excreted in human milk.110,111 Because many drugs are excreted in human milk, caution should be exercised when aminocaproic acid is administered to a nursing woman.110,111

Pediatric Use

Safety and efficacy of aminocaproic acid in pediatric patients have not been established.110,111

Aminocaproic acid injection contains benzyl alcohol as a preservative.111 Administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.114,115,116,117,118 Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates.114,115,116,117,118 Each mL of aminocaproic acid injection in multiple-dose vials contains 9 mg of benzyl alcohol.111 Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the 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, and pruritus.110,111

Anti-inhibitor coagulant complex and Factor IX complex

An increased risk of thrombosis may occur if aminocaproic acid is used concomitantly with anti-inhibitor coagulant complex or factor IX complex; concomitant use of these drugs should be avoided.110,111

Description

Aminocaproic acid is a synthetic lysine derivative that is an inhibitor of fibrinolysis.110,111,123 The drug has been shown to inhibit the activation of plasminogen and the action of plasmin.110,111 Aminocaproic acid inhibits the binding of plasmin to fibrin by occupying the lysine-binding sites of plasminogen.126

Aminocaproic acid is rapidly and completely absorbed from the GI tract; peak plasma concentrations are attained within about 1 hour following a 5-g oral dose.110,111 Plasma concentrations may be higher in patients with severe renal impairment.110,111 After prolonged administration, aminocaproic acid distributes through extravascular as well as intravascular compartments, penetrating human red blood cells and other body cells.110,111 The major portion of aminocaproic acid is not metabolized.110,111 The drug is eliminated principally in the urine as unchanged drug (65%) and the adipic acid metabolite (11%).110,111 The terminal elimination half-life of aminocaproic acid is approximately 2 hours.110,111 The drug is removed by hemodialysis and may be removed by peritoneal dialysis.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 supplements, as well as any concomitant illnesses.110,111
• Advise patients to inform their clinician 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.

Only references cited for selected revisions after 1984 are available electronically.

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