Aminocaproic Acid

Aminocaproic acid is a synthetic antifibrinolytic similar to tranexamic acid but weaker and needing more frequent dosing. It is used for bleeding from excess fibrinolysis, such as after surgery, in bleeding disorders, and after thrombolytic overdose. It is rarely available in East Africa, where tranexamic acid is used instead.

Classification. Antifibrinolytic; synthetic lysine analogue.

Mechanism. Blocks the lysine binding sites on plasminogen, preventing plasmin from attaching to fibrin and breaking down the clot.

Pharmacodynamics. Onset within an hour by mouth and within minutes IV. Plasma levels of 130 micrograms/mL are needed to inhibit fibrinolysis.

Pharmacokinetics. Oral bioavailability about 80% to 100%. Half life about 2 hours. About 65% excreted unchanged by the kidneys within 12 hours.

Acute bleeding from raised fibrinolysis, adult.

• Loading dose 4 to 5 g IV (or orally) over the first hour.

• Then 1 g/hour IV (or orally) for 8 hours or until bleeding is controlled.

• Maximum 30 g in 24 hours.

Prevention of bleeding in surgery, adult. 5 g IV before surgery, then 1 g/hour for 6 to 8 hours.

Hereditary bleeding disorders (dental procedures), adult. 50 mg/kg orally four times daily for 5 to 7 days; mouthwash 5% solution (10 mL for 2 minutes, four times daily).

Children (specialist). Loading 100 mg/kg IV or orally over the first hour, then 33.3 mg/kg/hour; maximum 18 g/m2 in 24 hours.

Kidney impairment. Reduce the dose to 25% of the usual dose in oliguria or advanced kidney impairment.

Contraindications. Active disseminated intravascular coagulation without heparin; upper urinary tract bleeding (clot obstruction); active thromboembolism; hypersensitivity.

Warnings. Myopathy and rhabdomyolysis with prolonged use (check creatine kinase); thrombosis; hypotension with rapid IV injection; bradycardia and arrhythmias; seizures; kidney failure; clot colic; do not give as a bolus.

Adverse effects. Nausea, diarrhoea, dizziness, tinnitus, headache, nasal congestion, hypotension, myopathy, rash.

Interactions. Combined oral contraceptives, oestrogens, prothrombin complex concentrates, factor concentrates: thrombosis risk. Thrombolytics: opposed effect.

Special groups.

• Pregnancy: limited data; use only when benefit outweighs risk.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change; sickle cell disease carries thrombosis and kidney risk, so use with caution.

• Older adults: check kidney function.

• Kidney impairment: reduce the dose to 25% of the usual dose in oliguria or advanced impairment.

• Liver impairment: no adjustment.

Formulations. Tablets 500 mg and 1000 mg; oral solution 250 mg/mL; injection 250 mg/mL.

Administration. Dilute IV doses in at least 5 times their volume with 0.9% sodium chloride, 5% glucose or Ringer solution; give the loading dose over 1 hour by pump. Oral doses may be taken with or without food.

Baseline. Haemoglobin, creatinine, creatine kinase, platelet count, fibrinogen, history of thrombosis, pregnancy status.

Monitoring. Bleeding; blood pressure and pulse during infusion; creatinine; creatine kinase in prolonged courses; muscle pain; signs of thrombosis.

Stopping. Stop when bleeding is controlled; do not continue beyond 8 hours at the loading regimen without review.

Common prescribing errors. Giving the loading dose too fast; not reducing the dose in kidney impairment; confusing the dose with tranexamic acid (about ten times more is needed); giving it in upper urinary tract bleeding; missing muscle toxicity.