Refludan (Lepirudin) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug interactions

Concomitant treatment with thrombolytics (eg, rt-PA or streptokinase) may

• increase the risk of bleeding complications
• considerably enhance the effect of REFLUDAN on aPTT prolongation.

(See also WARNINGS: Hemorrhagic Events, ADVERSE REACTIONS: Adverse Events Reported in Other Populations; Intracranial Bleeding and DOSAGE AND ADMINISTRATION: Monitoring and Adjusting Therapy; Concomitant Use With Thrombolytic Therapy.)

Concomitant treatment with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding (see also DOSAGE AND ADMINISTRATION: Monitoring and Adjusting Therapy; Use in Patients Scheduled for a Switch to Oral Anticoagulation).

OVERDOSAGE

In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.

No specific antidote for REFLUDAN is available. If life-threatening bleeding occurs and excessive plasma levels of lepirudin are suspected, the following steps should be followed:

• Immediately STOP REFLUDAN administration
• Determine aPTT and other coagulation levels as appropriate
• Determine hemoglobin and prepare for blood transfusion
• Follow the current guidelines for treating patients with shock

Individual clinical case reports and in vitro data suggest that either hemofiltration or hemodialysis (using high-flux dialysis membranes with a cutoff point of 50,000 daltons, eg, AN/69) may be useful in this situation.

In studies in pigs, the application of von Willebrand Factor (vWF, 66 IU/kg body weight) markedly reduced the bleeding time. The clinical significance of this data is unknown.

CONTRAINDICATIONS

REFLUDAN is contraindicated in patients with known hypersensitivity to hirudins or to any of the components in REFLUDAN [lepirudin (rDNA) for injection].