AMINOCAPROIC ACID- aminocaproic acid solution

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Active ingredient:
AMINOCAPROIC ACID (UNII: U6F3787206) (AMINOCAPROIC ACID - UNII:U6F3787206)
Available from:
Amneal Pharmaceuticals NY LLC
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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, 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 ). Aminocaproic acid should not be used when there is evi
Product summary:
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.
Authorization status:
Abbreviated New Drug Application
Authorization number:
69238-1596-8

AMINOCAPROIC ACID- aminocaproic acid solution

Amneal Pharmaceuticals NY LLC

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Aminocaproic Acid Oral Solution, USP

Rx only

DESCRIPTION

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.

CLINICAL PHARMACOLOGY

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,

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).

CONTRAINDICATIONS

Aminocaproic acid 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 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.

WARNINGS

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.

PRECAUTIONS

General

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.

Laboratory Tests

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.

Pregnancy

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.

Nursing Mothers

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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

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,

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 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.

OVERDOSAGE

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

12 grams.

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

follows:

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

been controlled.

HOW SUPPLIED

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.

REFERENCE

Stefanini M, Dameshek W: The Hemorrhagic Disorders, Ed. 2, New York, Grune and Stratton;

1962:510-514.

Distributed by:

Amneal Pharmaceuticals LLC

Bridgewater, NJ 08807

Rev. 03-2019-00

PRINCIPAL DISPLAY PANEL

AMINOCAPROIC ACID

aminocaproic acid solution

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 9 238 -159 6

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

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

Inactive Ingredients

Ingredient Name

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)

Product Characteristics

Color

S core

S hap e

S iz e

Flavor

RASPBERRY (natural and artificial raspberry flavo r)

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

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

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA21278 0

0 8 /23/20 19

Labeler -

Amneal Pharmaceuticals NY LLC (123797875)

Revised: 3/2019

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