indication

For treatment of heparin-induced thrombocytopenia and for the prevention of thrombosis. Bivalirudin is indicated for use in patients undergoing percutaneous coronary intervention (PCI), in patients at moderate to high risk acute coronary syndromes due to unstable angina or non-ST segment elevation in whom a PCI is planned.

pharmacology

Bivalirudin directly and reversibly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.

mechanism of action

Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.

toxicity

Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.

biotransformation

80% proteolytic cleavage

absorption

Following intravenous administration, bivalirudin exhibits linear pharmacokinetics . The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.

half life

* Normal renal function: 25 min (in normal conditions) * Creatinine clearance 10-29mL/min: 57min * Dialysis-dependant patients: 3.5h

route of elimination

Bivalirudin is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.

drug interactions

Deferasirox: Anticoagulants increase the risk for gastrointestinal ulceration/irritation and/or GI bleeding. If these two agents must be used, patients need to be closely monitored for signs and symptoms of GI toxicity.

Gemcitabine: Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Use extreme caution if using gemcitabine and bleomycin in combination. Monitor for the development of pulmonary toxicity.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of rivaroxaban. Avoid concurrent use of rivaroxaban with other anticoagulants whenever possible, other than during transition periods, due to the possible increased for bleeding.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Bivalirudin. Monitor for increased bleeding during concomitant thearpy.