Drug interactions- summary

Thrombolytics (eg. alterplase streptokinase) Lipirudin incr may increase the risk of bleeding complications 

Coumarin deriv. ( vitamin K antagonists ) Lepirudin incr platelet function may increase the risk of bleeding 

Thrombolytics (eg. alterplase streptokinase) Lipirudin incr concomittant treatment with thrombolytics may increase the risk of bleeding complications and considerably enhance the effect of lepirudin on a aPTT prolongation 

Coumarin deriv. ( vitamin K antagonists ) Lepirudin incr concomittant treatment with coumarins derivatives and drugs that affect platelet function may increase the risk of bleeding

Thrombocytopenia, heparin induced 

Hematologic

Bleeding was the most adverse frequent event Other hemorrhagic events- hemoperitonium, heoptysis, liver bleeding, lung bleeding, mouth bleeding retroperitoneal bleeding

Miscellaneous-

Fever, abnormal liver function, pneumonia, sepsis, allergic skin reactions, heart failure, abnormal kidney function, unspecified infections, multiorgan failure, pericardial effusion, ventricullar fibrillation

Known hypersenstivity

Special precautions-

Hemorrhagic events - As with other anticoagulants hemorrage can occur at any site in patients receiving lipirudin Antibiotics - formation of antihirudin bodies was observed in about of 40% of HIT (heparin induced thrombocytopenia ) treated with lepirudin. This may increase the anticoagulant efect of lepirudin possibly due to delayed renal elimination of active lepirudin- antihirudin complexes Hypersentivity reactions- reports of allergic and hypersenstivity reactions, including anaphylactic reactions. Serious reactions inn shock and death.

Renal function impairment- serious liver injury (eg. liver cirrhosis) may enhance the anticoagulant effect of lepirudin due to cagulation defects secondary to reduced generation of vitamin K dependent coagulation factors.

Lab test abnormalities- dosage ( infusion rate) should be adjusted according to aPTT ratio.

Thrombin- dependent coagulation assays are changed by lepirudin

Pregnancy- drug should be used during pregnancy only if needed Lactation- decide whether to disconinue nursing or discontinue the drug taking into account the importance of the drug to the mother

Children- safety and effectiveness in pediatric have not been established

Thrombocytopenia, heparin induced

Initial dosage-

0.4mg/kg body weight ( upto 110kg ) slowly IV (eg. over 15 to 20 seconds ) as a bolus dose followed by 0.15mg/kg body weight ( upto 110kg ) /hour as a continous IV infusion over 2 to 4 days or longer if clinically needed. Normally the initial dose is based on body weight.

This is valid up to weight of 110kg. In patients exceeding body weight 110kg the initial dose should not be increased beyond the 110kg body weight dose ( maximal initial bolus dose of 44mg maximal initial infusion dose of 16.5mg/hr )

Pharmacokinetics

Lepirudin is thought to bemetabolised by release of amino acids catabolic hydrolysis of the parent drug.

About 48% of the administered dose is excreted in the urine, which consists of unchanged drug ( 35%) and other fragments of parent drug

Pregnancy-

drug should be used during pregnancy only if needed

Lactation- decide whether to disconinue nursing or discontinue the drug taking into account the importance of the drug to the mother

Children- safety and effectiveness in pediatric have not been established