Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

AMINOCAPROIC ACID

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Aminocaproic acid is a synthetic amino acid which is similar in structure to lysine and ornithine. Aminocaproic acid is indicated in adults to enhance hemostasis when fibrinolysis contributes to bleeding, and to treat hemorrhage secondary to various disorders including aplastic anemia, abruptio placentae, hepatic cirrhosis, and neoplastic diseases.

Specific Substances

    1) Acepramin
    2) Acepramine
    3) ACS
    4) Amicar
    5) Amikar
    6) epsilon Aminocaproic Acid
    7) omega Aminocaproic Acid
    8) 6-Aminocaproic Acid
    9) omega Aminokapron
    10) Capramol
    11) Caprocid
    12) Caprolisin
    13) CL 10304
    14) CY 116
    15) EACA
    16) EACS
    17) Epsamon
    18) Epsicapron
    19) Epsikapron
    20) Epsilcapramin
    21) Epsilon S
    22) Hemocaprol
    23) Hemopar
    24) Hepin
    25) Ipsilon
    26) 177JD
    27) epsilon Leucine
    28) epsilon norleucine
    29) NSC 26154
    30) Respramin
    31) 6-Aminohexanoic acid
    32) CAS 60-32-2

Available Forms Sources

    A) FORMS
    1) Aminocaproic acid is available as 500 mg and 1000 mg tablets and 1.25 g/5 mL solution for oral administration (Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012). It is also available as 250 mg/mL IV solution (Prod Info aminocaproic acid intravenous injection, 2013).
    B) SOURCES
    1) Aminocaproic acid is a synthetic amino acid which is similar in structure to lysine and ornithine (Geltzeiler & Schwartz, 1984).
    C) USES
    1) Aminocaproic acid is indicated in adults to enhance hemostasis when fibrinolysis contributes to bleeding, and to treat hemorrhage secondary to various disorders including aplastic anemia, abruptio placentae, hepatic cirrhosis, and neoplastic diseases. Aminocaproic acid is not indicated in the treatment of fibrinolytic hemorrhage unless there is definite proof that diffuse intravascular coagulation (DIC) is not the underlying cause (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Aminocaproic acid is indicated in adults to enhance hemostasis when fibrinolysis contributes to bleeding, and to treat hemorrhage secondary to various disorders including aplastic anemia, abruptio placentae, hepatic cirrhosis, and neoplastic diseases.
    B) PHARMACOLOGY: Actions appear to be due to inhibition of plasminogen activator substances primarily, with some antiplasmin activity. It inhibits the activation of plasminogen to plasmin, thus inhibiting fibrinolysis.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Aminocaproic acid is generally well tolerated. Most side effects occur with long term, high dose therapy. Side effects include edema, headache, malaise, allergic and anaphylactoid reactions, anaphylaxis, bradycardia, hypotension, peripheral ischemia, thrombosis, abdominal pain, diarrhea, nausea, vomiting, agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia, increased CPK, muscle weakness, myalgia, myopathy, myositis, rhabdomyolysis, confusion, seizures, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope, dyspnea, nasal congestion, pulmonary embolism, pruritus, rash, tinnitus, decreased vision, watery eyes, increased BUN, and renal failure.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are anticipated to be an exaggeration of adverse effects following therapeutic doses. In a few cases of IV aminocaproic acid overdoses, adverse effects ranged from no reaction to transient hypotension to severe acute renal failure leading to death. Although a dose of 12 grams has caused acute renal failure, patients usually tolerate doses as high as 100 grams. Seizures developed in a patient with a history of brain tumor and seizures after receiving an 8-gram bolus injection of aminocaproic acid.
    0.2.20) REPRODUCTIVE
    A) Aminocaproic Acid is rated FDA Pregnancy Category C. Impaired fertility was observed in rats administered this drug at doses within the human therapeutic range.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following a significant overdose.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    D) Monitor hepatic enzymes, renal function, CPK, and CBC with differential and platelet count following a significant exposure.
    E) Obtain an ECG, and institute continuous cardiac monitoring following a significant overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine, if unresponsive to fluids. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. In patients with an acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg, filgrastim, sargramostim). Fresh whole blood transfusions, fibrinogen infusions, and other emergency measures should be considered in life-threatening situations.
    C) DECONTAMINATION
    1) PREHOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain their airway.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain their airway.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with persistent seizures or severe allergic reaction.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) Aminocaproic acid is removed by peritoneal dialysis with dialysis clearance accounting for 58% of total body clearance.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected aminocaproic acid overdose, the possibility of multi-drug involvement should be considered.
    I) PHARMACOKINETICS
    1) Tmax: 1 to 2 hours. Absorption: Readily absorbed from the gastrointestinal tract. Vd (oral): 23.1 +/1 6.6 L. Vd (IV): 30 +/- 8.2 L. Protein binding: Does not appear to be bound to plasma proteins. Renal clearance: 116 mL/min. Approximately 65% is recovered in the urine as unchanged drug. Elimination half-life: About 2 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause hypotension, hepatotoxicity, or seizures.

Range Of Toxicity

    A) TOXICITY: Cardiac and hepatic necrosis were reported in a postmortem examination of a patient who received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Seizures developed in a patient with a history of brain tumor and seizures after receiving 8 gram bolus injection of aminocaproic acid. Although a dose of 12 grams has caused acute renal failure, patients usually tolerate doses as high as 100 grams.
    B) THERAPEUTIC DOSE: ADULT: ORAL TABLETS: 5 g during the first hour of treatment, followed by 1 g per hour for about 8 hours or until the bleeding has stopped. ORAL SYRUP: 20 mL (5 g) during the first hour of treatment, followed by 5 mL (1.25 g) per hour for about 8 hours or until the bleeding has stopped. INTRAVENOUS: 16 to 20 mL (4 to 5 g) aminocaproic acid in 250 mL of diluent administered as an IV infusion during the first hour of treatment, followed by a continuous infusion rate of 4 mL (1 g) aminocaproic acid in 50 mL of diluent per hour for about 8 hours or until the bleeding has stopped. PEDIATRIC: The safety and efficacy of aminocaproic acid has not been established in pediatric patients.

Clinical Effects

Summary Of Exposure

    A) USES: Aminocaproic acid is indicated in adults to enhance hemostasis when fibrinolysis contributes to bleeding, and to treat hemorrhage secondary to various disorders including aplastic anemia, abruptio placentae, hepatic cirrhosis, and neoplastic diseases.
    B) PHARMACOLOGY: Actions appear to be due to inhibition of plasminogen activator substances primarily, with some antiplasmin activity. It inhibits the activation of plasminogen to plasmin, thus inhibiting fibrinolysis.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Aminocaproic acid is generally well tolerated. Most side effects occur with long term, high dose therapy. Side effects include edema, headache, malaise, allergic and anaphylactoid reactions, anaphylaxis, bradycardia, hypotension, peripheral ischemia, thrombosis, abdominal pain, diarrhea, nausea, vomiting, agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia, increased CPK, muscle weakness, myalgia, myopathy, myositis, rhabdomyolysis, confusion, seizures, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope, dyspnea, nasal congestion, pulmonary embolism, pruritus, rash, tinnitus, decreased vision, watery eyes, increased BUN, and renal failure.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are anticipated to be an exaggeration of adverse effects following therapeutic doses. In a few cases of IV aminocaproic acid overdoses, adverse effects ranged from no reaction to transient hypotension to severe acute renal failure leading to death. Although a dose of 12 grams has caused acute renal failure, patients usually tolerate doses as high as 100 grams. Seizures developed in a patient with a history of brain tumor and seizures after receiving an 8-gram bolus injection of aminocaproic acid.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) DECREASED VISION: Decreased vision and watery eyes have been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    2) CONJUNCTIVAL HYPEREMIA is occasionally noted when aminocaproic acid is given chronically (Anon, 1967).
    3.4.4) EARS
    A) WITH THERAPEUTIC USE
    1) TINNITUS: Tinnitus has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    3.4.5) NOSE
    A) WITH THERAPEUTIC USE
    1) Nasal congestion has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) Too rapid an administration rate has been associated with transient lowering of blood pressure of moderate degree (Personal Communication, 1983; Swartz, 1966).
    B) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) Bradycardia has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    C) EDEMA
    1) WITH THERAPEUTIC USE
    a) Edema has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    D) RIGHT HEART FAILURE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Right heart failure associated with pulmonary arterial obstruction has been reported in a 47-year-old treated with aminocaproic acid in a dose of 20 grams per day IV for 5 days (Johansson, 1967).
    E) MYOCARDIAL NECROSIS
    1) WITH THERAPEUTIC USE
    a) Cardiac and hepatic necrosis were reported in a postmortem examination of a patient who received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Cerebrovascular hemorrhage was the cause of death (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    F) PERIPHERAL ISCHEMIA
    1) WITH THERAPEUTIC USE
    a) Peripheral ischemia has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    G) SYNCOPE
    1) WITH THERAPEUTIC USE
    a) Syncope has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    H) THROMBOSIS
    1) WITH THERAPEUTIC USE
    a) Both renal artery thrombosis (Tubbs et al, 1979) and cerebral thrombosis (Hoffman & Koo, 1979) have been associated with aminocaproic acid therapy.
    b) Thrombosis has been reported with the use of aminocaproic acid. Inhibition of fibrinolysis by aminocaproic acid via inhibition of plasminogen activator substances may theoretically result in clotting or thrombosis (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PULMONARY EMBOLISM
    1) WITH THERAPEUTIC USE
    a) Pulmonary embolism has been reported with the use of aminocaproic acid (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012). It has been possibly associated with the use of 20 to 30 grams per day for 2 to 3 weeks (Jokowitz, 1974).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE REPORT: Dizziness, headache and vomiting followed by a grand mal seizure was observed in a 32-year-old hemophiliac following an IV infusion of 6 grams. A dose administered 6 months earlier had produced no complications (Feffer et al, 1978).
    B) DELIRIUM
    1) WITH THERAPEUTIC USE
    a) Delirium has been reported with the use of aminocaproic acid (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) Delirium consisting of visual, auditory, and kinesthetic hallucinations has been reported after a 2 gram IV dose (Wysenbeek et al, 1978).
    C) SEIZURE
    1) WITH THERAPEUTIC USE
    a) Seizures have been reported with the use of aminocaproic acid (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE REPORT: Dizziness, headache and vomiting followed by a grand mal seizure was observed in a 32-year-old hemophiliac following an IV infusion of 6 grams. A dose administered 6 months earlier had produced no complications (Feffer et al, 1978).
    2) WITH POISONING/EXPOSURE
    a) Seizures developed in a patient with a history of brain tumor and seizures after receiving 8 gram bolus injection of aminocaproic acid (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    D) HYDROCEPHALUS
    1) WITH THERAPEUTIC USE
    a) For treatment of subarachnoid hemorrhage, there are reports of increased incidence of neurologic deficits (hydrocephalus, cerebral ischemia, and cerebral vasospasm) with antifibrinolytic therapy; however, direct causality to aminocaproic acid has not been established (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE SERIES: One study reported that of 46 patients who received aminocaproic acid to prevent hemorrhage from intracranial aneurysms, 43% demonstrated dilated ventricles and 31% showed clinical evidence of hydrocephalus. Doses given were 2 grams every 2 hours for 5 to 51 days (Park, 1979).
    E) CEREBRAL ISCHEMIA
    1) WITH THERAPEUTIC USE
    a) For treatment of subarachnoid hemorrhage, there are reports of increased incidence of neurologic deficits (ie, hydrocephalus, cerebral ischemia, and cerebral vasospasm) with antifibrinolytic therapy; however, direct causality to aminocaproic acid has not been established (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    F) VASOSPASM
    1) WITH THERAPEUTIC USE
    a) For treatment of subarachnoid hemorrhage, there are reports of increased incidence of neurologic deficits (ie, hydrocephalus, cerebral ischemia, and cerebral vasospasm) with antifibrinolytic therapy; however, direct causality to aminocaproic acid has not been established (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    G) ACUTE INTRACRANIAL HYPERTENSION
    1) WITH THERAPEUTIC USE
    a) Intracranial hypertension has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    H) CEREBROVASCULAR ACCIDENT
    1) WITH THERAPEUTIC USE
    a) Stroke has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting have been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE REPORT: Dizziness, headache and vomiting followed by a grand mal seizure was observed in a 32-year-old hemophiliac following an IV infusion of 6 grams. A dose administered 6 months earlier had produced no complications (Feffer et al, 1978).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    C) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) Abdominal pain has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) HEPATIC FAILURE
    1) WITH THERAPEUTIC USE
    a) Hepatic failure has been associated with the administration of aminocaproic acid when cirrhosis has been present (AMA Division of Drugs, 1983).
    B) HEPATIC NECROSIS
    1) WITH THERAPEUTIC USE
    a) Cardiac and hepatic necrosis were reported in a postmortem examination of a patient who received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Cerebrovascular hemorrhage was the cause of death (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) MYOGLOBINURIA
    1) WITH THERAPEUTIC USE
    a) Myoglobinuria is a common occurrence in patients treated with high doses for long periods of time (Brodkin, 1980; Rizza, 1976).
    b) Rarely, skeletal muscle weakness with necrosis of muscle fibers has presented as muscle weakness and myalgia to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure with prolonged aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    B) RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) Renal failure with progression to oliguria or anuria is rare, but has been reported following usual IV or oral doses (Lingardh & Andersson, 1966; Charytan & Purtilo, 1969; Britt et al, 1980).
    b) Renal impairment is usually characterized by an increase in BUN or non-protein nitrogen (Charytan & Purtilo, 1969).
    c) Rarely, skeletal muscle weakness with necrosis of muscle fibers has presented as muscle weakness and myalgia to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure has occurred with prolonged aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    d) In one case, 75% of the glomeruli involved had diffuse thrombosis within capillary lumens (Charytan & Purtilo, 1969). Other cases have reported renal obstruction presumably due to blood clots (Hilgartner, 1966; Gobbi, 1967; Itterbeek, 1968; Haygood, 1971; Pitts et al, 1986).
    2) WITH POISONING/EXPOSURE
    a) In a few cases of IV aminocaproic acid overdoses, adverse effects ranged from no reaction to transient hypotension to severe acute renal failure leading to death. Although a dose of 12 grams caused acute renal failure, patients usually tolerate doses as high as 100 grams (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    C) URINARY TRACT OBSTRUCTION
    1) WITH THERAPEUTIC USE
    a) Aminocaproic acid therapy has been associated with intrarenal obstruction by causing glomerular capillary and clots in renal pelvis and ureter in patients with upper urinary tract bleeding (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE REPORT: Complete urinary tract obstruction of a solitary kidney was reported secondary to aminocaproic acid-induced fibrin clot formation in a 25-year-old male (Geltzeiler & Schwartz, 1984).
    D) ABNORMAL EJACULATION
    1) WITH THERAPEUTIC USE
    a) CASE SERIES: Four of 25 hemophiliac patients who were receiving 6 grams of aminocaproic acid every 2 hours developed inhibition of ejaculation with impotence. The earliest onset or recognition of the reaction was 24 hours after initiation of therapy. Resumption of normal sexual function was noted as soon as 6 hours post drug discontinuation (Evans & Aledort, 1978).
    E) SERUM BLOOD UREA NITROGEN RAISED
    1) WITH THERAPEUTIC USE
    a) Increased BUN levels have been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMORRHAGE
    1) WITH THERAPEUTIC USE
    a) High doses (36 to 48 grams daily) may prolong bleeding time and increase rebleeding in intraoperative hemorrhage in subarachnoid hemorrhage patients (Glick et al, 1981).
    b) After cessation of therapy with aminocaproic acid, fibrinolytic activity is not normal for 3 to 4 days (Burchiel & Schmer, 1981).
    B) AGRANULOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Agranulocytosis has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    C) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) Leukopenia has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    D) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenia has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    E) BLOOD COAGULATION DISORDER
    1) WITH THERAPEUTIC USE
    a) Coagulation disorder has been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Rash and pruritus have been reported with the use of aminocaproic acid (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) CASE REPORT: A case of morbilliform rash developed in a 59-year-old using aminocaproic acid therapeutically. Some of the lesions became purpuric (Dukes, 1981; Chakrabarti & Collett, 1980).
    B) INJECTION SITE REACTION
    1) WITH THERAPEUTIC USE
    a) Injection site reactions, including pan and necrosis, have been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) DRUG-INDUCED MYOPATHY
    1) WITH THERAPEUTIC USE
    a) Severe cases may be associated with muscle necrosis, myoglobinuria, rhabdomyolysis, and prolonged elevations of muscle enzymes (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012; Korsan-Bengtsen, 1969; Frank, 1972; Shaw & Miller, 1974; Rizza, 1976).
    b) Doses of up to 3 grams/day have been reported to be associated with symptoms of muscle pain, weakness, increased fatigability, and elevation of muscle enzymes.
    c) CASE REPORT: Necrotic myopathy was seen in a 20-year-old following 26 grams daily for 2 weeks followed by 36 grams daily for 6 more weeks. The patient complained of muscular pain and weakness. Biopsy revealed necrotic fibers and phagocytosis (Vanneste & van Wijngaarden, 1982).
    1) Muscle necrosis has also been observed (Biswas et al, 1980).
    d) CASE REPORT: Proximal myopathy was seen in a 20-year-old following therapy with 3 grams every 3 hours for 27 days (Morris et al, 1983).
    e) CASE REPORT: Myonecrosis was described in a 22-year-old man following aminocaproic acid therapy for traumatic hematuria. The dose was 4.5 grams every 6 hours for 3 weeks (Johnstone & Syme, 1987).
    B) RHABDOMYOLYSIS
    1) WITH THERAPEUTIC USE
    a) Rarely, skeletal muscle weakness with necrosis of muscle fibers has presented as muscle weakness and myalgia to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure has occurred with prolonged aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    b) Rhabdomyolysis has been seen in several cases. Muscle biopsy specimens showed no evidence of intravascular thrombosis, however, they did support direct myotoxicity (Britt et al, 1980).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Allergic reactions, including anaphylaxis and anaphylactoid reactions, have been reported with aminocaproic acid therapy (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Reproductive

    3.20.1) SUMMARY
    A) Aminocaproic Acid is rated FDA Pregnancy Category C. Impaired fertility was observed in rats administered this drug at doses within the human therapeutic range.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Aminocaproic acid is rated FDA Pregnancy Category C (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    2) Aminocaproic acid should only be administered during pregnancy if clearly needed (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is unknown whether aminocaproic acid is excreted in human milk. Exercise caution when administering aminocaproic acid to a nursing woman (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) RATS: Impaired fertility (decreased implantations, litter sizes, and number of pups born) was reported in female and male rats administered dietary doses equivalent to the maximum human therapeutic dose (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following a significant overdose.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    D) Monitor hepatic enzymes, renal function, CPK, and CBC with differential and platelet count following a significant exposure.
    E) Obtain an ECG, and institute continuous cardiac monitoring following a significant overdose.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Myopathy may occur, producing high plasma creatine kinase levels, and mild hyperbilirubinemia (Morris et al, 1983). Elevated aspartate transaminase (AST) and serum lactate dehydrogenase (LD) have also been noted (Kennard et al, 1980; Biswas et al, 1980).
    2) Serial creatinine phosphokinase (CPK) levels are important in monitoring a patient using aminocaproic acid. This is especially true if the therapy is in excess of 2 weeks and a total dose greater than 500 grams (Brown et al, 1982).
    4.1.3) URINE
    A) URINALYSIS
    1) HEMATURIA and PROTEINURIA have been seen in cases of acute renal failure due to aminocaproic acid (Biswas et al, 1980).
    B) OTHER
    1) Myopathy may produce myoglobinuria (Morris et al, 1983).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status following a significant overdose.
    C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    D) Monitor hepatic enzymes, renal function, CPK, and CBC with differential and platelet count following a significant exposure.
    E) Obtain an ECG, and institute continuous cardiac monitoring following a significant overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine, if unresponsive to fluids. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. In patients with an acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg, filgrastim, sargramostim). Fresh whole blood transfusions, fibrinogen infusions, and other emergency measures should be considered in life-threatening situations.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor vital signs and mental status following a significant overdose.
    3) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    4) Monitor hepatic enzymes, renal function, CPK, and CBC with differential and platelet count following a significant exposure.
    5) Obtain an ECG, and institute continuous cardiac monitoring following significant overdose.
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    E) MYELOSUPPRESSION
    1) There is little data on the use of hematopoietic colony stimulating factors to treat neutropenia after drug overdose or idiosyncratic reactions. These agents have been shown to shorten the duration of severe neutropenia in patients receiving cancer chemotherapy (Hartman et al, 1997; Stull et al, 2005). They have also been used to treat agranulocytosis induced by nonchemotherapy drugs (Beauchesne & Shalansky, 1999). They may be considered in patients with severe neutropenia who have or are at significant risk for developing febrile neutropenia.
    a) Filgrastim: The usual starting dose in adults is 5 micrograms/kilogram/day by intravenous infusion or subcutaneous injection (Prod Info NEUPOGEN(R) injection, 2006).
    b) Sargramostim: Usual dose is 250 micrograms/square meter/day infused IV over 4 hours (Prod Info LEUKINE(R) injection, 2006).
    c) Monitor CBC with differential.
    2) Fresh whole blood transfusions, fibrinogen infusions, and other emergency measures should be considered in life-threatening situations (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Enhanced Elimination

    A) PERITONEAL DIALYSIS
    1) Aminocaproic acid is removed by peritoneal dialysis with dialysis clearance accounting for 58% of total body clearance (Fish et al, 1981).

Range Of Toxicity

Summary

    A) TOXICITY: Cardiac and hepatic necrosis were reported in a postmortem examination of a patient who received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Seizures developed in a patient with a history of brain tumor and seizures after receiving 8 gram bolus injection of aminocaproic acid. Although a dose of 12 grams has caused acute renal failure, patients usually tolerate doses as high as 100 grams.
    B) THERAPEUTIC DOSE: ADULT: ORAL TABLETS: 5 g during the first hour of treatment, followed by 1 g per hour for about 8 hours or until the bleeding has stopped. ORAL SYRUP: 20 mL (5 g) during the first hour of treatment, followed by 5 mL (1.25 g) per hour for about 8 hours or until the bleeding has stopped. INTRAVENOUS: 16 to 20 mL (4 to 5 g) aminocaproic acid in 250 mL of diluent administered as an IV infusion during the first hour of treatment, followed by a continuous infusion rate of 4 mL (1 g) aminocaproic acid in 50 mL of diluent per hour for about 8 hours or until the bleeding has stopped. PEDIATRIC: The safety and efficacy of aminocaproic acid has not been established in pediatric patients.

Therapeutic Dose

    7.2.1) ADULT
    A) ACUTE BLEEDING SYNDROMES
    1) ORAL TABLETS: The recommended dose is 5 g during the first hour of treatment, followed by 1 g per hour for about 8 hours or until the bleeding has stopped (Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    2) ORAL SYRUP: The recommended dose is 20 mL (5 g) during the first hour of treatment, followed by 5 mL (1.25 g) per hour for about 8 hours or until the bleeding has stopped (Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).
    3) INTRAVENOUS: The recommended dose is 16 to 20 mL (4 to 5 g) aminocaproic acid in 250 mL of diluent administered as an IV infusion during the first hour of treatment, followed by a continuous infusion rate of 4 mL (1 g) aminocaproic acid in 50 mL of diluent per hour for about 8 hours or until the bleeding has stopped (Prod Info aminocaproic acid injection, 2007).
    7.2.2) PEDIATRIC
    A) The safety and efficacy of aminocaproic acid has not been established in pediatric patients (Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012; Prod Info aminocaproic acid injection, 2007).

Minimum Lethal Exposure

    A) Cardiac and hepatic necrosis were reported in a postmortem examination of a patient who received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g. Cerebrovascular hemorrhage was the cause of death (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Maximum Tolerated Exposure

    A) It is recommended that patients on therapy for longer than 2 weeks and with total doses of greater than 500 grams should be monitored carefully for renal, hepatic, or muscle toxicity (Brown et al, 1982).
    B) Seizures developed in a patient with a history of brain tumor and seizures after receiving 8 gram bolus injection of aminocaproic acid. Although a dose of 12 grams has caused acute renal failure, patients usually tolerate doses as high as 100 grams (Prod Info aminocaproic acid intravenous injection, 2013; Prod Info AMINOCAPROIC ACID oral tablets, syrup, 2012).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) THERAPEUTIC PLASMA LEVEL - 130 micrograms per milliliter (Pagliaro & Levin, 1979)

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 14,300 mg/kg (RTECS , 1990)
    B) LD50- (INTRAPERITONEAL)RAT:
    1) 7000 mg/kg (RTECS , 1990)
    C) LD50- (ORAL)RAT:
    1) 13,000 mg/kg (RTECS , 1990)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Actions appear to due to inhibition of plasminogen activator substances primarily, with some antiplasmin activity (Prod Info, 1987). It inhibits the activation of plasminogen to plasmin, thus inhibiting fibrinolysis (Brown et al, 1982).

Physicochemical

Physical Characteristics

    A) This compound is almost odorless and colorless (JEF Reynolds , 1990).

Ph

    A) A 20% solution has an approximate pH of 7.5-8.0. The injectable (USP) has a pH of 6-7.6 (JEF Reynolds , 1990).

Molecular Weight

    A) 131.2

References

General Bibliography

    1) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    2) AMA Division of Drugs: AMA Drug Evaluations, 5th ed, American Medical Association, Chicago, IL, 1983.
    3) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    4) Anon: Today's drugs: epsilon aminocaproic acid. BMJ 1967; 2:725-726.
    5) Banerjee A, Stoica C, & Walia A: Acute hyperkalemia as a complication of intravenous therapy with epsilon-aminocaproic acid. J Clin Anesth 2011; 23(7):565-568.
    6) Beauchesne MF & Shalansky SJ: Nonchemotherapy drug-induced agranulocytosis: a review of 118 patients treated with colony-stimulating factors. Pharmacotherapy 1999; 19(3):299-305.
    7) Biswas CK, Milligan DAR, & Agte SD: Acute renal failure and myopathy after treatment with aminocaproic acid. Br Med J 1980; 281:115-116.
    8) Britt CW, Light RR, & Peters BH: Rhabdomyolysis during treatment with epsilon-aminocaproic acid. Arch Neurol 1980; 37:187-188.
    9) Brodkin HM: Myoglobinuria following epsilon aminocaproic acid (EACA) therapy. Case report. J Neurosurg 1980; 53:690-692.
    10) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    11) Brown JA, Wollmann RL, & Mullan S: Myopathy induced by epsilon-aminocaproic acid. J Neurosurg 1982; 57:130-134.
    12) Budavari S: The Merck Index, 11th ed, Merck & Co, Inc, Rahway, NJ, 1989.
    13) Burchiel KJ & Schmer G: A method for monitoring antifibrinolytic therapy in patients with ruptured intracranial aneurysms. J Neurosurg 1981; 54:12-15.
    14) Chakrabarti A & Collett KA: Purpuric rash due to epsilon-aminocaproic acid. Br Med J 1980; 197-198.
    15) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    16) Charytan C & Purtilo D: Glomerular capillary thrombosis and acute renal failure after epsilon aminocaproic acid therapy. N Engl J Med 1969; 280:1102.
    17) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    18) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    19) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    20) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    21) Dukes MNG: Meyler's side effects of drugs, Ann 5, Excerpta Medica, New York, NY, 1981.
    22) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    23) Evans BE & Aledort LM: Inhibition of ejaculation due to epsilon amino-caproic acid. N Engl J Med 1978; 298:166-167.
    24) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    25) Feffer SE, Parray HR, & Westring DL: Seizure after infusion of aminocaproic acid. JAMA 1978; 240:2468.
    26) Fish SS, Pancobo S, & Berkseth R: Pharmacokinetics of epsilon-aminocaproic acid during peritoneal dialysis. J Neurosurg 1981; 54:736-739.
    27) Frank MM: Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study. N Engl Med 1972; 286:808.
    28) Frederiksen MC, Bowsher DJ, & Ruo TI: Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrionlytic effects in normal subjects. Clin Pharmacol Ther 1984; 35:387-393.
    29) Geltzeiler J & Schwartz D: Obstruction of solitary kidney due to epsilon-aminocaproic acid-induced fibrin clot formation. Urology 1984; 24:64-66.
    30) Glick R, Green D, & Ts'ao C: High dose epsilon-aminocaproic acid prolongs the bleeding time and increases rebleeding and intraoperative hemorrhage in patients with subarachnoid hemorrhage. Neurosurgery 1981; 9:398-401.
    31) Gobbi F: Use and misuse of aminocaproic acid. Lancet 1967; 2:472.
    32) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    33) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    34) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    35) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    36) Hartman LC, Tschetter LK, Habermann TM, et al: Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.. N Engl J Med 1997; 336:1776-1780.
    37) Haygood TA: Aminocaproic acid treatment of prolonged hematuria following renal biopsy. Arch Intern Med 1971; 127:478.
    38) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    39) Hilgartner MW: Intrarenal obstruction in haemophilia. Lancet 1966; 1:486.
    40) Hoffman EP & Koo AH: Cerebral thrombosis associated with Amicar(R) therapy. Radiology 1979; 131:687-689.
    41) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    42) Itterbeek H: High obstruction of urine flow as a complication of the treatment with fibrinolysis inhibitors of hematuria in hemophilics. Acta Hemat 1968; 39:237.
    43) JEF Reynolds : Aminocaproic acid. Martindale: The Extra Pharmacopoeia (electronic version). The Pharmaceutical Press. Greenwood Village, CO (Internet Version). Edition expires 1990; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    44) Johansson SA: Acute right heart failure during treatment with epsilon and aminocaproic acid (EACA). Acta Med Scand 1967; 182:331.
    45) Johnstone BR & Syme RRA: Myonecrosis complicating epsilon aminocaproic acid treatment of traumatic haematuria. Br J Urol 1987; 60:81-82.
    46) Jokowitz S: Ipsilon aminocaproic acid and possible pulmonary emboli. N Engl J Med 1974; 290:861.
    47) Kennard C, Swash M, & Henson RA: Myopathy due to epsilon amino-caproic acid. Muscle Nerve 1980; 3:202-206.
    48) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    49) Korsan-Bengtsen K: Extensive muscle necrosis after long-term treatment with aminocaproic acid (EACA) in a case of hereditary periodic edema. Acta Med Scand 1969; 185:341.
    50) Lingardh G & Andersson L: Clot retention in the kidneys as a probable cause of anuria during treatment of haematuria with epsilon-aminocaproic acid. Acta Med Scand 1966; 180:649.
    51) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    52) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    53) McNicol GP, Fletcher AP, & Alkjaersig N: The use of epsilon aminocaproic acid a potent inhibitor of fibronolytic activity, in the management of post operative hematuria. J Urol 1961; 86:829-837.
    54) Morris CDW, Jacobs P, & Berman PA: Epsilon-aminocaproic acid-induced myopathy. S Afr Med J 1983; 64:363-366.
    55) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    56) Pagliaro LA & Benet LZ: Pharmacokinetic Data. J Pharmacokinet Biopharm 1975; 3:333-383.
    57) Pagliaro LA & Levin RH: Problems in Pediatric Drug Therapy, Drug Intell Pub, Hamilton, IL, 1979.
    58) Park BE: Spontaneous subarachnoid hemorrhage complicated by communicating hydrocephalus: epsilon amino caproic acid as a possible predisposing factor. Surg Neurol 1979; 11:73-80.
    59) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    60) Perazella MA & Biswas P: Acute hyperkalemia associated with intravenous epsilon-aminocaproic acid therapy. Am J Kidney Dis 1999; 33(4):782-785.
    61) Personal Communication: Personal Communication: Mary Russo, Pharm D. Lederle Laboratories, 1983.
    62) Pitts TO, Spero JA, & Bontempo FA: Acute renal failure due to high-grade obstruction following therapy with epsilon-aminocaproic acid. Am J Kid Dis 1986; 8:441-444.
    63) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    64) Product Information: AMINOCAPROIC ACID oral tablets, syrup, aminocaproic acid oral tablets, syrup. VersaPharm Inc. (per DailyMed), Marietta, GA, 2012.
    65) Product Information: LEUKINE(R) injection, sargramostim injection. Berlex, Seattle, WA, 2006.
    66) Product Information: NEUPOGEN(R) injection, filgrastim injection. Amgen,Inc, Thousand Oaks, CA, 2006.
    67) Product Information: aminocaproic acid injection, aminocaproic acid injection. American Regent, Inc., Shirley, NY, 2007.
    68) Product Information: aminocaproic acid intravenous injection, aminocaproic acid intravenous injection. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    69) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    70) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    71) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    72) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    73) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1990; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    74) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    75) Rizza RA: Myoglobinuria following aminocaproic acid administration. JAMA 1976; 236:1845.
    76) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    77) Shaw MDM & Miller JD: Epsilon-aminocaproic acid and subarachnoid haemorrhage. Lancet 1974; 2:847-848.
    78) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    79) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2010; 14(2):162-168.
    80) Stull DM, Bilmes R, Kim H, et al: Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm 2005; 62(1):83-87.
    81) Swartz C: Cardiac and renal hemodynamic effects of the antifibrinolytic agents, epsilon aminocaproic acid. Curr Ther Res 1966; 8:336.
    82) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    83) Tubbs RR, Benjamin SP, & Dohn DE: Recurrent subarachnoid hemorrhage associated with aminocaproic acid therapy and acute renal artery thrombosis. Case report. J Neurosurg 1979; 51:94-97.
    84) Vanneste JAL & van Wijngaarden GK: Epsilon-aminocaproic acid myopathy. Report of a case and literature review. Eur Neurol 1982; 21:242-248.
    85) Wysenbeek AJ, Sella A, Vardi M, et al: Acute delirious state after E-aminocaproic acid. Lancet 1978; 1:221.