Aminocaproic acid (injection): Difference between revisions

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{{drugbox
{{DrugProjectFormSinglePage
|authorTag={{Alonso}}
|genericName=Aminocaproic acid
|aOrAn=a
|drugClass=hemostatic
|indicationType=treatment
|indication=acute bleeding syndromes due to elevated [[fibrinolytic]] activity
|adverseReactions=[[abdominal pain]], [[nausea]], [[vomiting]], [[diarrhea]], [[headache]] [[dizziness]], [[confusion]], [[hallucinations]], [[blurred vision]], [[tinnitus]]
|blackBoxWarningTitle=Warning Title
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
|fdaLIADAdult======Acute Bleeding Syndromes due to Elevated Fibrinolytic Activity=====
======Dosing Information======
* Aminocaproic acid injection is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, [[Sodium Chloride]] Injection 0.9%, [[Dextrose]] Injection 5% or [[Ringer’s]] Injection).  Although Sterile Water for Injection is compatible for intravenous injection, the resultant solution is hypo-osmolar.  Rapid injection of aminocaproic acid injection undiluted into a vein is not recommended.
* For the treatment of acute bleeding syndromes due to elevated [[fibrinolytic]] activity, it is suggested that 16 to 20 mL (4 to 5 g) of aminocaproic acid injection in 250 mL of diluent be administered by infusion during the first hour of treatment, followed by a continuing infusion at the rate of 4 mL (1 g) per hour in 50 mL of diluent.  This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled. * Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Aminocaproic acid in adult patients.
|offLabelAdultNoGuideSupport======Intraocular Hemorrhage=====
 
* Dosing Information
 
:* 100 mg/kg PO q4h.<ref name="pmid6870623">{{cite journal| author=McGetrick JJ, Jampol LM, Goldberg MF, Frenkel M, Fiscella RG| title=Aminocaproic acid decreases secondary hemorrhage after traumatic hyphema. | journal=Arch Ophthalmol | year= 1983 | volume= 101 | issue= 7 | pages= 1031-3 | pmid=6870623 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6870623  }} </ref>
 
=====Postoperative Hemorrhage Prophylaxis=====
 
* Dosing Information
 
:* Administer 3 boluses (10 gram each) of epsilon-aminocaproic acid (EACA) diluted in saline solution 0.9% (total volume 40mL) after anesthesia induction, administration of protamine  and administration of heparin in the pump.<ref name="pmid8028387">{{cite journal| author=Daily PO, Lamphere JA, Dembitsky WP, Adamson RM, Dans NF| title=Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study. | journal=J Thorac Cardiovasc Surg | year= 1994 | volume= 108 | issue= 1 | pages= 99-106; discussion 106-8 | pmid=8028387 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8028387  }} </ref>
 
=====Dental Procedure Hemorrhage Prophylaxis and Treatment in Hemophilic Patients=====
 
* Dosing information
 
:* 100 mg/kg 4 to 6 hours after surgery PO to a maximum dose of 6 g q6h.<ref name="pmid8579061">{{cite journal| author=Djulbegovic B, Marasa M, Pesto A, Kushner GM, Hadley T, Joseph G et al.| title=Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B. | journal=Am J Hematol | year= 1996 | volume= 51 | issue= 2 | pages= 168-70 | pmid=8579061 | doi=10.1002/(SICI)1096-8652(199602)51:2<168::AID-AJH14>3.0.CO;2-E | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8579061  }} </ref>
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Aminocaproic acid in pediatric patients.
|offLabelPedNoGuideSupport======Post-Surgery Intraocular Hemorrhage=====
 
* Dosing Information
 
:* 5 g 60 minutes before surgery, then 5 g q6h.<ref name="pmid3883968">{{cite journal| author=de Bustros S, Glaser BM, Michels RG, Auer C| title=Effect of epsilon-aminocaproic acid on postvitrectomy hemorrhage. | journal=Arch Ophthalmol | year= 1985 | volume= 103 | issue= 2 | pages= 219-21 | pmid=3883968 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3883968  }} </ref>
|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 Iysis test is abnormal in [[primary fibrinolysis]] but normal in [[DIC]].
 
AMICAR 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 Iysis 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 Iysis 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.
 
=====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. 
* 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.
|clinicalTrials=Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported:
* '''General''': [[Edema]], [[headache]], [[malais]]e.
* '''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]], [[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.
|FDAPregCat=C
|useInPregnancyFDA=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.
|useInNursing=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 AMICAR is administered to a nursing woman.
|useInPed=Safety and effectiveness in pediatric patients have not been established.
|useInRenalImpair=Higher plasma concentrations of aminocaproic acid may occur in patients with severe [[renal failure]].
|administration=Intravenous
|IVCompat=Aminocaproic acid injection is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% or Ringer’s Injection).
|overdose=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]].
|drugBox={{Drugbox2
| verifiedrevid = 476999776
| IUPAC_name = 6-aminohexanoic acid
| IUPAC_name = 6-aminohexanoic acid
| image = 6-Aminocaproic acid.png
| image = Aminocaproic01.jpg
 
<!--Clinical data-->
| tradename =  Amicar
| Drugs.com = {{drugs.com|monograph|aminocaproic_acid}}
| MedlinePlus = a608023
| pregnancy_category = 
| legal_status = Rx-only
| routes_of_administration = 
 
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = [[Renal]]
| elimination_half-life = 2 hours
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 60-32-2
| CAS_number = 60-32-2
| ATC_prefix = B02
| ATC_prefix = B02
| ATC_suffix = AA01
| ATC_suffix = AA01
| ATC_supplemental =  
| ATC_supplemental =
| PubChem = 564
| PubChem = 564
| DrugBank = APRD00791
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| C=6 | H=13 | N=1 | O=2
| DrugBank = DB00513
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 548
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = U6F3787206
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00160
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16586
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1046
| NIAID_ChemDB = 018631
 
<!--Chemical data-->
| C=6 | H=13 | N=1 | O=2  
| molecular_weight = 131.173 g/mol
| molecular_weight = 131.173 g/mol
| bioavailability =  
| smiles = O=C(O)C(N)CCCC
| protein_bound =  
| InChI = 1/C6H13NO2/c1-2-3-4-5(7)6(8)9/h5H,2-4,7H2,1H3,(H,8,9)
| metabolism = [[Renal]]
| InChIKey = LRQKBLKVPFOOQJ-UHFFFAOYAT
| elimination_half-life = 2 hours
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =  
| StdInChI = 1S/C6H13NO2/c7-5-3-1-2-4-6(8)9/h1-5,7H2,(H,8,9)
| legal_status =  
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration =  
| StdInChIKey = SLXKOJJOQWFEFD-UHFFFAOYSA-N
}}
}}
{{SI}}
|mechAction=The fibrinolysis-inhibitory effects of aminocaproic acid appear to be exerted principally via inhibition of [[plasminogen activator]]s and to a lesser degree through antiplasmin activity.
{{CMG}}
|structure=Aminocaproic acid is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.


{{EH}}
Its chemical structure is:


'''Aminocaproic acid''' (also known as Amicar, є-amino caproic acid, or 6-aminohexanoic acid) is a derivative and analogue of the [[amino acid]] [[lysine]], which makes it an effective [[enzyme inhibitor|inhibitor]] for [[enzyme|enzymes]] which bind that particular residue. Such enzymes include [[proteolytic]] enzymes (which break down [[protein|proteins]]) including [[plasminogen]], the enzyme responsible for [[fibrinolysis]]. For this reason it is effective in treatment of some [[coagulopathy|bleeding disorders]] and is marketed as Amicar.
[[File:Aminocaproic01.jpg|600px|thumbnail|left]]
{{clr}}


==Mechanism of action==
Aminocaproic acid is soluble in water, acid, and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform.
Aminocaproic acid works as an anti-fibrinolytic or anti-proteolytic. As a lysine [[analogue]], it binds reversibly to the [[kringle domain]] of the enzyme [[plasminogen]] and blocks binding of [[fibrin]], which is normally activated to [[plasmin]].


==Clinical use==
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.
Aminocaproic acid is used to treat excessive postoperative bleeding. It can be given orally or intravenously. One scenario where it may be useful is to treat bleeding after dental extractions in patients with [[hemophilia]], because the [[oral mucosa]] is rich in plasminogen activators.  A meta-analysis found that lysine analogs like aminocaproic acid significantly reduced blood loss in patients undergoing coronary artery bypass grafting.


===Side effects===
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]].
Its side effects are mainly related to the [[gastrointestinal tract]] and include nausea, vomiting, abdominal pain, and diarrhea. It may cause generalised [[myalgia]]. The main risk associated with aminocaproic acid is the increased risk for [[thrombosis]] because of the inhibition of fibrinolysis.


==Other uses==
Aminocaproic Acid is soluble in water, acid and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform.
Aminocaproic Acid Injection, USP, for intravenous administration, is a sterile pyrogen-free solution containing 250 mg/mL of aminocaproic acid with Benzyl Alcohol 0.9%, as a preservative, and Water for Injection q.s.  The pH is adjusted to approximately 6.8 with Hydrochloric Acid and/or Sodium Hydroxide.
|PD=There is limited information regarding Pharmacodynamics of aminocaproic acid in the drug label.
|PK=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.


Aminocaproic acid is occasionally used in [[BN-PAGE]] [[buffer solution|buffers]], not for its effects as a proteolysis inhibitor, but to solubilize [[membrane protein|membrane proteins]] in place of [[sodium chloride]] (which is incompatible with PAGE in the necessary concentration). Percent recovery of [[protein complex|protein complexes]] increases linearly with the concentration of inhibitor (between 125 mM and 750 mM)<ref>Schägger, H and Von Jagow, G (1991). Blue Native Electrophoresis for Isolation of Membrane Protein Complexes in Enzymatically Active Form. ''Analytical Biochemistry 199'' (2): 223-231.</ref>.
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.


==References==
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.


<references/>
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.
 
|nonClinToxic=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.
{{Antihemorrhagics}}
|howSupplied======Aminocaproic Acid Injection=====
{{SIB}}
* Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F).
 
|fdaPatientInfo=There is limited information regarding Patient Counseling Information of aminocaproic acid in the drug label.
[[Category:Amino acids]]
|alcohol=Alcohol-Aminocaproic acid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
[[Category:Antifibrinolytics]]
|brandNames=* AMINOCAPROIC ACID®<ref>{{Cite web | title =AMINOCAPROIC ACID- aminocaproic acid injection, solution  | url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4f65667-c349-420b-b7b7-f20f3a4e4d4e }}</ref>
[[Category:Hematology]]
|lookAlike=* Amicar - Omacor
 
* Aminocaproic acid - Amino acids
[[ja:Ε-アミノカプロン酸]]
|nlmPatientInfo=(Link to patient information page)
[[pl:Kwas ε-aminokapronowy]]
|drugShortage=Drug Shortage
 
}}
 
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Latest revision as of 00:31, 18 May 2015

Aminocaproic acid (injection)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

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Overview

Aminocaproic acid (injection) is a hemostatic that is FDA approved for the treatment of acute bleeding syndromes due to elevated fibrinolytic activity. Common adverse reactions include abdominal pain, nausea, vomiting, diarrhea, headache dizziness, confusion, hallucinations, blurred vision, tinnitus.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acute Bleeding Syndromes due to Elevated Fibrinolytic Activity
Dosing Information
  • Aminocaproic acid injection is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% or Ringer’s Injection). Although Sterile Water for Injection is compatible for intravenous injection, the resultant solution is hypo-osmolar. Rapid injection of aminocaproic acid injection undiluted into a vein is not recommended.
  • For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 16 to 20 mL (4 to 5 g) of aminocaproic acid injection in 250 mL of diluent be administered by infusion during the first hour of treatment, followed by a continuing infusion at the rate of 4 mL (1 g) per hour in 50 mL of diluent. This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled. * Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aminocaproic acid in adult patients.

Non–Guideline-Supported Use

Intraocular Hemorrhage
  • Dosing Information
  • 100 mg/kg PO q4h.[1]
Postoperative Hemorrhage Prophylaxis
  • Dosing Information
  • Administer 3 boluses (10 gram each) of epsilon-aminocaproic acid (EACA) diluted in saline solution 0.9% (total volume 40mL) after anesthesia induction, administration of protamine and administration of heparin in the pump.[2]
Dental Procedure Hemorrhage Prophylaxis and Treatment in Hemophilic Patients
  • Dosing information
  • 100 mg/kg 4 to 6 hours after surgery PO to a maximum dose of 6 g q6h.[3]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Aminocaproic acid (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aminocaproic acid in pediatric patients.

Non–Guideline-Supported Use

Post-Surgery Intraocular Hemorrhage
  • Dosing Information
  • 5 g 60 minutes before surgery, then 5 g q6h.[4]

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 Iysis test is abnormal in primary fibrinolysis but normal in DIC.

AMICAR 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 Iysis 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 Iysis 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.

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.
  • 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.

Adverse Reactions

Clinical Trials Experience

Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported:

Postmarketing Experience

There is limited information regarding Aminocaproic acid (injection) Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Aminocaproic acid (injection) Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C 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.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aminocaproic acid (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Aminocaproic acid (injection) during labor and delivery.

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 AMICAR is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

There is no FDA guidance on the use of Aminocaproic acid (injection) in geriatric settings.

Gender

There is no FDA guidance on the use of Aminocaproic acid (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Aminocaproic acid (injection) with respect to specific racial populations.

Renal Impairment

Higher plasma concentrations of aminocaproic acid may occur in patients with severe renal failure.

Hepatic Impairment

There is no FDA guidance on the use of Aminocaproic acid (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Aminocaproic acid (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Aminocaproic acid (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

Intravenous

Monitoring

There is limited information regarding Aminocaproic acid (injection) Monitoring in the drug label.

IV Compatibility

Aminocaproic acid injection is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% or Ringer’s Injection).

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.

Pharmacology

Template:Px
Aminocaproic acid (injection)
Systematic (IUPAC) name
6-aminohexanoic acid
Identifiers
CAS number 60-32-2
ATC code B02AA01
PubChem 564
DrugBank DB00513
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 131.173 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Metabolism Renal
Half life 2 hours
Excretion ?
Therapeutic considerations
Pregnancy cat.

?

Legal status

Template:Unicode Prescription only

Routes ?

Mechanism of Action

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.

Structure

Aminocaproic acid is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.

Its chemical structure is:

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

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.

Aminocaproic Acid is soluble in water, acid and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform. Aminocaproic Acid Injection, USP, for intravenous administration, is a sterile pyrogen-free solution containing 250 mg/mL of aminocaproic acid with Benzyl Alcohol 0.9%, as a preservative, and Water for Injection q.s. The pH is adjusted to approximately 6.8 with Hydrochloric Acid and/or Sodium Hydroxide.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of aminocaproic acid in the drug label.

Pharmacokinetics

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.

Nonclinical Toxicology

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.

Clinical Studies

There is limited information regarding Aminocaproic acid (injection) Clinical Studies in the drug label.

How Supplied

Aminocaproic Acid Injection
  • Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F).

Storage

There is limited information regarding Aminocaproic acid (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of aminocaproic acid in the drug label.

Precautions with Alcohol

Alcohol-Aminocaproic acid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • AMINOCAPROIC ACID®[5]

Look-Alike Drug Names

  • Amicar - Omacor
  • Aminocaproic acid - Amino acids

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ McGetrick JJ, Jampol LM, Goldberg MF, Frenkel M, Fiscella RG (1983). "Aminocaproic acid decreases secondary hemorrhage after traumatic hyphema". Arch Ophthalmol. 101 (7): 1031–3. PMID 6870623.
  2. ↑ Daily PO, Lamphere JA, Dembitsky WP, Adamson RM, Dans NF (1994). "Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study". J Thorac Cardiovasc Surg. 108 (1): 99–106, discussion 106-8. PMID 8028387.
  3. ↑ Djulbegovic B, Marasa M, Pesto A, Kushner GM, Hadley T, Joseph G; et al. (1996). "Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B." Am J Hematol. 51 (2): 168–70. doi:10.1002/(SICI)1096-8652(199602)51:2<168::AID-AJH14>3.0.CO;2-E. PMID 8579061.
  4. ↑ de Bustros S, Glaser BM, Michels RG, Auer C (1985). "Effect of epsilon-aminocaproic acid on postvitrectomy hemorrhage". Arch Ophthalmol. 103 (2): 219–21. PMID 3883968.
  5. ↑ "AMINOCAPROIC ACID- aminocaproic acid injection, solution".

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