Bivalirudin

Bivalirudin is a synthetic 20-amino acid analogue of the naturally occurring hirudin. It is a specific and reversible direct thrombin inhibitor that works by binding to the catalytic and anionic exosite of circulating and clot-bound thrombin. 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.

The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions. In in vitro studies, bivalirudin inhibited both soluble (free) and clot-bound thrombin and was not neutralized by products of the platelet release reaction.

• Anticoagulant in patients undergoing PTCA/PCI
• PCI with HIT/HITTS (heparin-induced thrombocytopenia/thrombosis syndrome)
• Unstable angina/Non-ST-Elevation MI (off-label)
• STEMI undergoing primary PCI (off-label)
• Heparin-induced thrombocytopenia

PCI/PTCA: IV Bolus: 0.75 mg/kg, then infusion: 1.75 mg/kg/h for the duration of the PCI procedure. Obtain ACT 5 minutes after bolus and administer additional 0.3 mg/kg bolus if indicated.

HIT/HITTS: IV Bolus: 0.75 mg/kg, followed by continuous infusion at 1.75 mg/kg/h for the duration of the procedure.

Post-procedure: Infusion may be continued for up to 4 hours post-procedure as indicated. After 4 hours, an additional infusion of 0.2 mg/kg/h for up to 20 hours may be given if needed.

Concomitant Therapy: Intended for use with aspirin (300-325 mg/day).

Renal Impairment:
CrCl 30-50 mL/min: Infusion rate 1.75 mg/kg/h
CrCl <30 mL/min: Reduce infusion rate to 1 mg/kg/h
Hemodialysis: Reduce infusion rate to 0.25 mg/kg/h (no reduction in bolus dose needed)

Hepatic impairment: No dosage adjustment needed.

Common: Bleeding (bruising), hypotension, nausea, headache, fever, infection, sepsis.

Cardiovascular: Hypotension, syncope, vascular anomaly, ventricular fibrillation.

Nervous: Cerebral ischemia, confusion, facial paralysis.

Respiratory: Lung edema.

Urogenital: Kidney failure, oliguria.

Elderly patients experienced more bleeding events than younger patients.

• Bleeding events: Most bleeding occurs at the arterial puncture site, but hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit should lead to consideration of a hemorrhagic event and cessation of bivalirudin.
• Use with caution in patients with conditions associated with increased bleeding risk.
• Coronary artery brachytherapy: Increased risk of thrombus formation with bivalirudin use in gamma brachytherapy.
• Notify your doctor if you see blood in vomit, urine, or stool (black, tarry stools or bright red blood).
• Caution with other anticoagulants.

• Active major bleeding
• CrCl <30 mL/min and dialysis-dependent patients
• Severe uncontrolled hypertension
• Subacute bacterial endocarditis
• Hypersensitivity (e.g., anaphylaxis) to bivalirudin or its components

• May increase risk of bleeding when used with thrombolytics, oral anticoagulants, or drugs that affect platelet function.
• Co-administration with heparin, warfarin, thrombolytics, or GPIs was associated with increased risks of major bleeding events.
• Do not mix with the following drugs in the same IV line: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, dobutamine, prochlorperazine, reteplase, streptokinase, vancomycin.