NEODOSE

INDICATIONS

• Hemorrhage Prophylaxis Cardiopulmonary bypass (CPB):In a neonatal subgroup analysis (n=4426) of a large observational study (n=22,258), aminocaproic acid had greater bleeding requiring surgical intervention compared with aprotinin. There was higher blood loss with aminocaproic acid (46 mL/kg) compared with aprotinin (36 mL/kg), but no differences in need for transfusion or requirement for surgical revision in 235 neonates who underwent CPB in a nonrandomized study. There was no difference in blood loss, requirement for surgical revision due to bleeding, or need for transfusion between tranexamic acid and aminocaproic acid in 105 neonates who underwent CPB in a nonrandomized study. Various dosing regimens are available. A pharmacokinetic study in 10 neonates proposed 40 mg/kg IV loading dose followed by 30 mg/kg/hr infusion and a priming dose of 100 mg/L. In clinical studies, 75 mg/kg IV over 10 minutes was administered at the beginning and end of CPB. Additionally, 75 mg/100 mL was added to the priming volume of the CPB system. A pharmacokinetic study identified the following regimen to achieve therapeutic concentrations: 75 mg/kg IV loading dose over 10 minutes followed by 75 mg/kg/hr IV until the end of surgery. Additionally, add 75 mg/kg in the priming volume of the CPB system (venous reservoir)
• Hemorrhage Prophylaxis Extracorporeal membrane oxygenation (ECMO):Empiric bleeding protocols included aminocaproic acid 100 mg/kg followed by 30 mg/kg/hr. Duration of infusion was for 72 hours or longer if bleeding persisted or shorter when cannula was removed. Administration was either directly to the patient or through the ECMO circuit . Surgical site bleeding was reduced with aminocaproic acid (7%) compared with no aminocaproic acid (12%). However, aminocaproic acid did not reduce the incidence of neonatal intracranial hemorrhage compared with no aminocaproic acid in 2 studies (n=327). Reduced circuit times due to clotting may not be a concern, as a retrospective analysis of 164 patients on ECMO demonstrated that a bleeding protocol, which included aminocaproic acid, did not shorten circuit times

CONTRAINDICATIONS

Contraindicated in DIC without concomitant heparin.

PRECAUTIONS

Intrarenal obstruction and glomerular capillary thrombosis has been reported in patients with upper urinary tract bleeding. Avoid use in patients with hematuria of upper urinary tract origin or use with caution if benefit of therapy outweighs the risk. Rare cases of skeletal muscle weakness, necrosis of muscle fibers, and rhabdomyolysis have been reported with prolonged administration. Neurological deficits, including hydrocephalus, cerebral ischemia, and cerebral vasospasm, have been reported with the use of antifibrinolytic agents in patients with subarachnoid hemorrhage (causality is unknown). Only use when hyperfibrinolysis (hyperplasminemia) has been definitively diagnosed. Rapid injection may result in hypotension, bradycardia, and/or arrhythmia. Thrombophlebitis may occur. Avoid concomitant use with factor IX complex concentrates or anti-inhibitor coagulant concentrate. Injection contains benzyl alcohol, which has been associated with serious adverse effects, including death, in neonates and low-birth-weight infants;

ADVERSE EFFECTS

Renal risk (28.6% vs 36.8%), renal injury (3.6% vs 9.5%), renal failure (1.4% vs 1.2%), vascular thrombosis (12.1% vs 8.4%), seizures (2.9% vs 3.2%), intracranial bleeding (3.6% vs 4.2%), stroke (1.4% vs 0%), and in-hospital mortality (6.4% vs 8.4%) occurred in 235 neonates undergoing cardiopulmonary bypass and administration of aminocaproic acid and aprotinin, respectively. A fatal case of aortic thrombosis in a neonate on extracorporeal life support and receiving aminocaproic acid occurred.

ADMINISTRATION

IV:

Rapid administration of undiluted injection into a vein is not recommended . The manufacturer recommends a concentration of 16 to 20 mg/mL

MONITORING

Monitor CPK levels in patients on long-term therapy. Assess the amount of fibrinolysis present during therapy