United States - English - NLM (National Library of Medicine)
AMINOCAPROIC ACID- aminocaproic acid solution
Amneal Pharmaceuticals NY LLC
Aminocaproic Acid Oral Solution, USP
Aminocaproic acid, USP is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.
Its chemical structure is:
Aminocaproic acid, USP is freely soluble in water, in acid, and in alkaline solutions, slightly soluble in
methanol and in alcohol, practically insoluble in chloroform and in ether.
Aminocaproic acid oral solution, USP for oral administration, contains 0.25 g/mL of aminocaproic acid,
USP with methylparaben 0.20%, propylparaben 0.05%, edetate disodium 0.30% as preservatives and the
following inactive ingredients: sodium saccharin, sorbitol, citric acid anhydrous, glycerin, propylene
glycol, purified water, natural and artificial raspberry flavor.
The fibrinolysis-inhibitory effects of aminocaproic acid appear to be exerted principally via inhibition
of plasminogen activators and to a lesser degree through antiplasmin activity.
In adults, oral absorption appears to be a zero-order process with an absorption rate of 5.2 g/hr. The
mean lag time in absorption is 10 minutes. After a single oral dose of 5 g, absorption was complete
(F=1). Mean ± SD peak plasma concentrations (164 ± 28 mcg/mL) were reached within 1.2 ± 0.45 hours.
After oral administration, the apparent volume of distribution was estimated to be 23.1 ± 6.6 L (mean ±
SD). Correspondingly, the volume of distribution after intravenous administration has been reported to
be 30.0 ± 8.2 L. After prolonged administration, aminocaproic acid has been found to distribute
throughout extravascular and intravascular compartments of the body, penetrating human red blood cells
as well as other tissue cells.
Renal excretion is the primary route of elimination. Sixty-five percent of the dose is recovered in the
urine as unchanged drug and 11% of the dose appears as the metabolite adipic acid. Renal clearance
(116 mL/min) approximates endogenous creatinine clearance. The total body clearance is 169 mL/min.
The terminal elimination half-life for aminocaproic acid is approximately 2 hours.
INDICATIONS AND USAGE
Aminocaproic acid oral solution is useful in enhancing hemostasis when fibrinolysis contributes to
bleeding. In life-threatening situations, transfusion of appropriate blood products and other emergency
measures may be required.
Fibrinolytic bleeding may frequently be associated with surgical complications following heart surgery
(with or without cardiac bypass procedures) and portacaval shunt; hematological disorders such as
amegakaryocytic thrombocytopenia (accompanying aplastic anemia); acute and life-threatening abruptio
placentae; hepatic cirrhosis; and neoplastic disease such as carcinoma of the prostate, lung, stomach,
Urinary fibrinolysis, usually a normal physiological phenomenon, may contribute to excessive urinary
tract fibrinolytic bleeding associated with surgical hematuria (following prostatectomy and
nephrectomy) or nonsurgical hematuria (accompanying polycystic or neoplastic diseases of the
genitourinary system (see WARNINGS).
Aminocaproic acid should not be used when there is evidence of an active intravascular clotting
When there is uncertainty as to whether the cause of bleeding is primary fibrinolysis or disseminated
intravascular coagulation (DIC), this distinction must be made before administering aminocaproic acid.
The following tests can be applied to differentiate the two conditions:
Platelet count is usually decreased in DIC but normal in primary fibrinolysis.
Protamine paracoagulation test is positive in DIC; a precipitate forms when protamine sulfate is
dropped into citrated plasma. The test is negative in the presence of primary fibrinolysis.
The euglobulin clot lysis test is abnormal in primary fibrinolysis but normal in DIC.
Aminocaproic acid must not be used in the presence of DIC without concomitant heparin.
In patients with upper urinary tract bleeding, aminocaproic acid administration has been known to cause
intrarenal obstruction in the form of glomerular capillary thrombosis or clots in the renal pelvis and
ureters. For this reason, aminocaproic acid should not be used in hematuria of upper urinary tract origin,
unless the possible benefits outweigh the risk.
Subendocardial hemorrhages have been observed in dogs given intravenous infusions of 0.2 times the
maximum human therapeutic dose of aminocaproic acid and in monkeys given 8 times the maximum
human therapeutic dose of aminocaproic acid.
Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of
aminocaproic acid at 0.8 to 3.3 times the maximum human therapeutic dose and in monkeys given
intravenous doses of aminocaproic acid at 6 times the maximum human therapeutic dose.
Rarely, skeletal muscle weakness with necrosis of muscle fibers has been reported following
prolonged administration. Clinical presentation may range from mild myalgias with weakness and fatigue
to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure. Muscle
enzymes, especially creatine phosphokinase (CPK) are elevated. CPK levels should be monitored in
patients on long-term therapy. Aminocaproic acid administration should be stopped if a rise in CPK is
noted. Resolution follows discontinuation of aminocaproic acid; however, the syndrome may recur if
aminocaproic acid is restarted.
The possibility of cardiac muscle damage should also be considered when skeletal myopathy occurs.
One case of cardiac and hepatic lesions observed in man has been reported. The patient received 2 g of
aminocaproic acid every 6 hours for a total dose of 26 g. Death was due to continued cerebrovascular
hemorrhage. Necrotic changes in the heart and liver were noted at autopsy.
Aminocaproic acid inhibits both the action of plasminogen activators and to a lesser degree, plasmin
activity. The drug should NOT be administered without a definite diagnosis and/or laboratory finding
indicative of hyperfibrinolysis (hyperplasminemia).
Inhibition of fibrinolysis by aminocaproic acid may theoretically result in clotting or thrombosis.
However, there is no definite evidence that administration of aminocaproic acid has been responsible
for the few reported cases of intravascular clotting which followed this treatment. Rather, it appears
that such intravascular clotting was most likely due to the patient's preexisting clinical condition, e.g.,
the presence of DIC. It has been postulated that extravascular clots formed in vivo may not undergo
spontaneous lysis as do normal clots.
Reports have appeared in the literature of an increased incidence of certain neurological deficits such
as hydrocephalus, cerebral ischemia, or cerebral vasospasm associated with the use of antifibrinolytic
agents in the treatment of subarachnoid hemorrhage (SAH). All of these events have also been
described as part of the natural course of SAH, or as a consequence of diagnostic procedures such as
angiography. Drug relatedness remains unclear.
Aminocaproic acid should not be administered with Factor IX Complex concentrates or Anti-Inhibitor
Coagulant concentrates, as the risk of thrombosis may be increased.
The use of aminocaproic acid should be accompanied by tests designed to determine the amount of
fibrinolysis present. There are presently available: (a) general tests such as those for the determination
of the lysis of a clot of blood or plasma; and (b) more specific tests for the study of various phases of
the fibrinolytic mechanisms. These latter tests include both semiquantitative and quantitative techniques
for the determination of profibrinolysin, fibrinolysin, and antifibrinolysin.
Drug Laboratory Test Interactions
Prolongation of the template bleeding time has been reported during continuous intravenous infusion of
aminocaproic acid at dosages exceeding 24 g/day. Platelet function studies in these patients have not
demonstrated any significant platelet dysfunction. However, in vitro studies have shown that at high
concentrations (7.4 mMol/L or 0.97 mg/mL and greater) aminocaproic acid inhibits ADP and collagen-
induced platelet aggregation, the release of ATP and serotonin, and the binding of fibrinogen to the
platelets in a concentration-response manner. Following a 10 g bolus of aminocaproic acid, transient
peak plasma concentrations of 4.6 mMol/L or 0.60 mg/mL have been obtained. The concentration of
aminocaproic acid necessary to maintain inhibition of fibrinolysis is 0.99 mMol/L or 0.13 mg/mL.
Administration of a 5 g bolus followed by 1 to 1.25 g/hr should achieve and sustain plasma levels of
0.13 mg/mL. Thus, concentrations which have been obtained in vivo clinically in patients with normal
renal function are considerably lower than the in vitro concentrations found to induce abnormalities in
platelet function tests. However, higher plasma concentrations of aminocaproic acid may occur in
patients with severe renal failure.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of aminocaproic acid and studies to
evaluate its mutagenic potential have not been conducted. Dietary administration of an equivalent of the
maximum human therapeutic dose of aminocaproic acid to rats of both sexes impaired fertility as
evidenced by decreased implantations, litter sizes and number of pups born.
Animal reproduction studies have not been conducted with aminocaproic acid. It is also not known
whether aminocaproic acid can cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity. Aminocaproic acid should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when aminocaproic acid is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported:
General: Edema, headache, malaise.
Hypersensitivity Reactions: Allergic and anaphylactoid reactions, anaphylaxis.
Cardiovascular: Bradycardia, hypotension, peripheral ischemia, thrombosis.
Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting.
Hematologic: Agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia.
Musculoskeletal: CPK increased, muscle weakness, myalgia, myopathy (see WARNINGS), myositis,
Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension,
Respiratory: Dyspnea, nasal congestion, pulmonary embolism.
Skin: Pruritis, rash.
Special Senses: Tinnitus, vision decreased, watery eyes.
Urogenital: BUN increased, renal failure. There have been some reports of dry ejaculation during the
period of aminocaproic acid treatment. These have been reported to date only in hemophilia patients
who received the drug after undergoing dental surgical procedures. However, this symptom resolved
in all patients within 24 to 48 hours of completion of therapy.
To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-
835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A few cases of acute overdosage with aminocaproic acid administered intravenously have been
reported. The effects have ranged from no reaction to transient hypotension to severe acute renal
failure leading to death. One patient with a history of brain tumor and seizures experienced seizures
after receiving an 8 gram bolus injection of aminocaproic acid. The single dose of aminocaproic acid
causing symptoms of overdosage or considered to be life-threatening is unknown. Patients have
tolerated doses as high as 100 grams while acute renal failure has been reported following a dose of
The intravenous and oral LD50 of aminocaproic acid were 3.0 and 12.0 g/kg, respectively, in the mouse
and 3.2 and 16.4 g/kg, respectively, in the rat. An intravenous infusion dose of 2.3 g/kg was lethal in the
dog. On intravenous administration, tonic-clonic convulsions were observed in dogs and mice.
No treatment for overdosage is known, although evidence exists that aminocaproic acid is removed by
hemodialysis and may be removed by peritoneal dialysis. Pharmacokinetic studies have shown that total
body clearance of aminocaproic acid is markedly decreased in patients with severe renal failure.
DOSAGE AND ADMINISTRATION
An identical dosage regimen may be followed by administering aminocaproic acid oral solution as
For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that
20 milliliter of aminocaproic acid oral solution (5 g) be administered during the first hour of treatment,
followed by a continuing rate of 5 milliliter of aminocaproic acid oral solution (1.25 g) per hour. This
method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has
Aminocaproic acid oral solution USP, 0.25 g/mL
Each mL of raspberry-flavored oral solution contains 0.25 g/mL of aminocaproic acid, USP.
8 Fl. Oz. (236.5 mL) Bottle with child-resistant closure – NDC 69238-1596-8
Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP
Controlled Room Temperature]. Dispense in Tight Containers; Do Not Freeze.
Stefanini M, Dameshek W: The Hemorrhagic Disorders, Ed. 2, New York, Grune and Stratton;
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807
PRINCIPAL DISPLAY PANEL
aminocaproic acid solution
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:6 9 238 -159 6
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
AMINO CAPRO IC ACID (UNII: U6 F378 720 6 ) (AMINOCAPROIC ACID - UNII:U6 F378 720 6 )
AMINOCAPROIC ACID 0 .25 g in 1 mL
Stre ng th
METHYLPARABEN (UNII: A2I8 C7HI9 T)
PRO PYLPARABEN (UNII: Z8 IX2SC1OH)
EDETATE DISO DIUM (UNII: 7FLD9 1C8 6 K)
SACCHARIN SO DIUM (UNII: SB8 ZUX40 TY)
Amneal Pharmaceuticals NY LLC
SO RBITO L (UNII: 50 6 T6 0 A25R)
ANHYDRO US CITRIC ACID (UNII: XF417D3PSL)
PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)
WATER (UNII: 0 59 QF0 KO0 R)
RASPBERRY (UNII: 4N14V5R27W)
GLYCERIN (UNII: PDC6 A3C0 OX)
S hap e
S iz e
RASPBERRY (natural and artificial raspberry flavo r)
NDC:6 9 238 -
159 6 -8
236 .5 mL in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n
Pro duc t
0 8 /23/20 19
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
0 8 /23/20 19
Amneal Pharmaceuticals NY LLC (123797875)