Generic Name :

Lepirudin ( recombinant hirudin )

Trade name:

Refludan

Action:

Direct Thrombin inhibitor

Indication:

Anticoagulation in-patients with strongly suspected or confirmed heparin induced thrombocytopenia (type II)

Prior to use of lepirudin a hematology consult should be obtained.

Administration and Dosage  :

Lepirudin is administered with or without an IV bolus followed by a continuous IV infusion

Bolus Dose:

Not recommended. Consider in cases of life or limb threatening thrombosis: 0.2mg/kg up to a initial maximum of 22mg over 15 to 20 seconds. No bolus is necessary if aPTT is 1.5-2 times baseline(aPTT 50-70)

Maintenance Infusion:

0.1mg/kg/hr up to a initial maximum of 11mg/hr for 2 to 10 days or as clinical situation warrants.

Goal :

aPTT 1.5 to 2times patients baseline

Lepirudin is excreted by renal mechanisms and must be adjusted in-patients with a CrCl <60 ml/min.or a serum creatinine > 1.5mg/dl .

Dose for Renal impairment:

  Not recommended in renal dysfunction

Loading Dose :

0.2mg/kg up to a maximum of 22mg over 15 to 20 seconds

Maintenance Infusion :

When starting Coumadin :

Adjust lepirudin dose to slightly above 1.5 baseline aPTT and when INR of 2.0 is obtained discontinue lepirudin

Concomitant use of thrombolytics :

Bolus Dose; 0.2mg/kg body weight

Infusion Rate: 0.1mg/kg/hour

Important:

The risk of intracranial bleeding is increased in-patients using thrombolytics and lepirudin.

Cardiopulmonary bypass :

0.2mg/kg lepirudin added to the prime and a 0.025mg/kg intravenous bolus followed by a continuous infusion of 0.5mg/min beginning 5 minutes prior to cannulation for CPB.

Line Flushes :

1mg lepirudin per flush.

Dosage adjustments:

4 hours after the infusion is started an aPTT should be obtained:

If aPTT > 2.5 baseline hold infusion for 2 hours and reinstitute at 50% of the original infusion dose recheck aPTT in 4 more hours.

If aPTT < 1.5 baseline increase infusion rate by 20%, recheck aPTT

in 4 hours if aPTT still subtherapeutic, increase infusion by another 20%.

If the maximum dose of 16.5mg/hr is reached assess for other factors that may be preventing an adequate response.

Standard Concentrations:

Standard Concentration is 1mg/ml.

100mg/100ml Normal saline

250mg/250ml Normal Saline

MICROINFUSION: 50mg/50ml

EW Standard

Standard Concentration is 1mg/ml.

100mg/100ml (1mg/ml) Normal saline

250mg/250ml (1mg/ml) Normal Saline

Special considerations :

Always obtain a baseline aPTT prior to initiating therapy:

If measured aPTT is 2.5 or greater than control do not start lepirudin

Monitor aPTT every 4 hours until two consecutive aPTT values are within the therapeutic range

Once a stable dose is achieved draw aPTT once a day

Do not adjust dosage without a current, valid aPTT

Serum Creatinine should be closely monitored to ensure proper dosing

The half-life of lepirudin is approximately 1.3 hours in normal individuals.

An aPTT should be obtained prior to procedures where anticoagulation is not desired to confirm that the drug has been eliminated.

Precautions:

The possibility of intracranial bleeds with thrombolytics and lepirudin is increased.

Do not use in patients with a recent history of:

Stroke, bleeding ulcers , severe uncontrolled hypertension, recent puncture of large vessels, or organ biopsy, bacterial endocarditis , advanced renal impairment, recent major surgery.

Do not use in hemodialysis patients. Lepirudin is not dialyzable

Side Effects :

Bronchospasm, stridor, dyspnea cough common

Unspecified allergic reactions, skin reactions, anaphylactoid and anaphylactic reactions, uncommon and facial edema, angioedema, tongue edema and laryngeal edema rare.

Note:

Lepirudin is antigenic and can result in hirudin-antibody complexes that are highly active and may prolong or shorten the drugs effect.

Antibody formation may compromise the ability to use lepirudin a second time after exposure.