AMICAR

R_x only

AMICAR (aminocaproic acid) is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.

Its chemical structure is:

AMICAR is soluble in water, acid, and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform.

AMICAR (aminocaproic acid) Oral Solution for oral administration, contains 0.25 g/mL of aminocaproic acid with methylparaben 0.20%, propylparaben 0.05%, edetate disodium 0.30% as preservatives and the following inactive ingredients: sodium saccharin, sorbitol solution, citric acid anhydrous, natural and artificial raspberry flavor and an artificial bitterness modifier.

Each AMICAR (aminocaproic acid) Tablet, for oral administration contains 500 mg or 1000 mg of aminocaproic acid and the following inactive ingredients: povidone, crospovidone, stearic acid, and magnesium stearate.

The fibrinolysis-inhibitory effects of AMICAR 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, AMICAR 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 AMICAR is approximately 2 hours.

AMICAR 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, and cervix.

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.)

AMICAR should not be used when there is evidence of an active intravascular clotting process.

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 AMICAR.

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.

AMICAR must not be used in the presence of DIC without concomitant heparin.

In patients with upper urinary tract bleeding, AMICAR 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, AMICAR 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 AMICAR and in monkeys given 8 times the maximum human therapeutic dose of AMICAR.

Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of AMICAR at 0.8 to 3.3 times the maximum human therapeutic dose and in monkeys given intravenous doses of AMICAR 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. AMICAR administration should be stopped if a rise in CPK is noted. Resolution follows discontinuation of AMICAR; however, the syndrome may recur if AMICAR 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.

AMICAR 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, rhabdomyolysis.

Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope.

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 AMICAR 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.

A few cases of acute overdosage with AMICAR 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 AMICAR. The single dose of AMICAR 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 12 grams.

The intravenous and oral LD₅₀ of AMICAR 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 AMICAR is removed by hemodialysis and may be removed by peritoneal dialysis. Pharmacokinetic studies have shown that total body clearance of AMICAR is markedly decreased in patients with severe renal failure.

An identical dosage regimen may be followed by administering AMICAR Tablets or AMICAR Oral Solution as follows:

For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 5 AMICAR 1000 mg Tablets or 10 AMICAR 500 mg Tablets (5 g) or 20 milliliter of AMICAR Oral Solution (5 g) be administered during the first hour of treatment, followed by a continuing rate of 1 AMICAR 1000 mg Tablet or 2 AMICAR 500 mg Tablets (1 g) or 5 milliliter of AMICAR 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 been controlled.

Product: 68151-3023

NDC: 68151-3023-1 1 TABLET in a BLISTER PACK

¹ Stefanini M, Dameshek W: The Hemorrhagic Disorders, Ed. 2, New York, Grune and Stratton; 1962:510-514.

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Marietta, GA 30062

Code 909B00
Rev. 05/15