Acepramin - General Information
An antifibrinolytic agent that acts by inhibiting plasminogen activators which have fibrinolytic properties.
Pharmacology of Acepramin
Aminocaproic acid works as an antifibrinolytic. It is a derivative of the amino acid lysine. 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.
Acepramin for patients
AMICAR Injection contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal "Gasping Syndrome.".
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.
Drug Laboratory Test Interactions
Prolongation of the template bleeding time has been reported during continuous intravenous infusion of AMICAR 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) EACA 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 AMICAR, transient peak plasma concentrations of 4.6 mMol/L or 0.60 mg/mL have been obtained. The concentration of AMICAR 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 AMICAR may occur in patients with severe renal failure.
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 D.C. a precipitate forms when protamine sulphate 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.
Additional information about Acepramin
Acepramin Indication: For use in the treatment of excessive postoperative bleeding.
Mechanism Of Action: Aminocaproic acid binds reversibly to the kringle domain of plasminogen and blocks the binding of plasminogen to fibrin and its activation to plasmin.
Drug Interactions: Not Available
Food Interactions: Take without regard to meals.
Generic Name: Aminocaproic Acid
Synonyms: Aminocaproate; ACS; Aminocaproic
Drug Category: Antifibrinolytic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Aminocaproic Acid: Acepramin; Acepramine; Afibrin; Amicar; Amikar; Aminokapron; Atsemin; Caplamin; Capracid; Capramol; Capranol; Caprocid; Caprolisin; EACA; EACS; Epsamon; Epsicapron; Epsikapron; Epsilcapramin; Epsilcapramine; Hemocaprol; Hemopar; Hepin; Ipsilon; Respramin;
Absorption: Absorbed rapidly following oral administration. 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).
Toxicity (Overdose): A few cases of acute overdosage with intravenous administration have been reported. The effects have ranged from no reaction to transient hypotension to severe acute renal failure leading to death. The intravenous and oral LD50 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.
Protein Binding: Not Available
Biotransformation: 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.
Half Life: The terminal elimination half-life is approximately 2 hours.
Dosage Forms of Acepramin: Injection, solution Intravenous
Chemical IUPAC Name: 6-aminohexanoic acid
Chemical Formula: C6H13NO2
Aminocaproic Acid on Wikipedia: http://en.wikipedia.org/wiki/Aminocaproic_acid
Organisms Affected: Humans and other mammals