NOTE: This dosing is for a patient with a creatinine clearance > 60 mL/min. The dose for a patient with renal insufficiency is determined in the next section.
Monitoring of lepirudin uses a ratio of the activated prothrombin time test (aPTT) and the mean of the normal reference range.
aPTT ratio =
= (patient's aPTT result in second) / (mean of normal reference aPTT in seconds)
Therapy with lepirudin should not be started if the aPTT ratio is >= 2.5 prior to therapy initiation.
Initial dosing of lepirudin for the patient with normal renal function:
(1) A bolus dose is given at a rate of 0.4 mg/kg, up to a maximum dose of 44 mg (achieved at a body weight of 110 kg). This is given over 15 to 20 seconds.
(2) An infusion of 0.15 mg/kg/h is started, up to a maximum of 16.5 mg/h (achieved at a body weight of 110 kg).
The aPTT ratio is determined at 4 hours after initiating therapy. The target ratio is 2. If the ratio is < 1.5 or > 2.5, then the testing is repeated before any adjustments are made to the infusion rate.
If the ratio is > 2.5:
(1) Stop the infusion for 2 hours.
(2) Decrease the infusion rate by 50%.
(3) Repeat the aPTT ratio in 4 hours.
If the ratio is < 1.5:
(1) Increase the infusion rate by 20%, not to exceed 0.21 mg/kg/h. (If this is limited to an upper weight of 110 kilograms, as the other doses are, then this would be 23.1 mg/h).
(2) Repeat the aPTT ratio in 4 hours.
(3) If the patient reaches the upper infusion level of 0.21 mg/kg/h without improvement of the aPTT ratio, then the patient should be investigated for coagulation abnormalities leading to a hypercoagulable state.
Many patients will develop anti-lepirudin antibodies, which may limit repeat usage.
