Bivalirudin

Approved Indications:

• Percutaneous Coronary Intervention (PCI):
  As an anticoagulant in patients undergoing PCI, including patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA).
• Unstable Angina/NSTEMI or STEMI:
  In combination with aspirin and clopidogrel or other antiplatelets in patients with unstable angina or myocardial infarction undergoing urgent or early invasive procedures.
• Heparin-Induced Thrombocytopenia (HIT):
  In patients with or at risk of HIT undergoing PCI, as it is a direct thrombin inhibitor and does not interact with heparin antibodies.

Off-Label (Clinically Accepted) Uses:

• Extracorporeal Membrane Oxygenation (ECMO):
  As an alternative anticoagulant to heparin in patients requiring ECMO with or at risk of HIT.
• Left Ventricular Assist Devices (LVAD):
  Used for anticoagulation in patients with HIT or heparin intolerance.
• Atrial Fibrillation Ablation Procedures:
  Employed as a procedural anticoagulant during catheter ablation in patients intolerant to heparin.

General Administration:

• Route: Intravenous (IV) bolus followed by continuous infusion.
• Initial Dose (for PCI):
• Bolus: 0.75 mg/kg IV
• Infusion: 1.75 mg/kg/hour for the duration of the procedure.
• Post-Procedure: Continue at 1.75 mg/kg/hour for up to 4 hours, then optionally reduce to 0.25 mg/kg/hour if necessary.

HIT Patients Undergoing PCI:

• Bolus: 0.75 mg/kg IV
• Infusion: 1.75 mg/kg/hour during PCI, adjusted per ACT monitoring.

Renal Impairment:

• CrCl <30 mL/min:
  Infusion rate reduced to 1.0 mg/kg/hour.
• Hemodialysis Patients:
  Infusion rate reduced to 0.25 mg/kg/hour.
• ACT monitoring is recommended.

Pediatrics & Elderly:
Limited data; individualized dosing and close monitoring are essential in off-label pediatric use. Elderly patients may require dose adjustments due to renal function decline.

Bivalirudin is a synthetic, specific, and reversible direct thrombin inhibitor. It binds both to the catalytic site and the anion-binding exosite of thrombin, thereby preventing thrombin from cleaving fibrinogen into fibrin, inhibiting clot formation. Unlike heparin, which requires antithrombin III for activity, Bivalirudin acts directly on both free and clot-bound thrombin. This mechanism provides predictable anticoagulation and reduced risk of heparin-induced thrombocytopenia (HIT), making it a safer alternative in high-risk cardiovascular interventions.

• Absorption: Administered intravenously; complete bioavailability.
• Distribution: Volume of distribution ~0.2 L/kg.
• Metabolism: Primarily by proteolytic cleavage; not significantly metabolized via liver enzymes.
• Elimination Half-Life:
• ~25 minutes in patients with normal renal function.
• Excretion: Approximately 20% renal excretion; the rest metabolized by plasma proteases.
• Onset of Action: Rapid—within minutes of IV administration.
• Steady State: Achieved rapidly due to short half-life.

• Pregnancy:
  No assigned FDA category under the current PLLR system. Animal studies show no teratogenicity; however, human data are limited. Use only if potential benefit justifies risk.
• Lactation:
  Unknown if Bivalirudin is excreted in human breast milk. Caution advised; consider discontinuing breastfeeding or the drug depending on clinical necessity.

• Primary Class: Anticoagulant
• Subclass: Direct Thrombin Inhibitor (DTI)
• Generation: Synthetic hirudin analog

• Known hypersensitivity to Bivalirudin or any component of the formulation.
• Active major bleeding.
• Severe uncontrolled hypertension.
• History of bleeding diathesis.

• Bleeding Risk:
  Monitor closely for bleeding; adjust dose in renal impairment.
• Hypersensitivity Reactions:
  Anaphylaxis and other severe allergic responses may occur.
• Renal Impairment:
  Requires dose adjustment; monitor renal function and ACT.
• Hematologic Monitoring:
  Monitor ACT or aPTT to guide dosing during procedures.
• Post-PCI Bleeding:
  Caution during arterial sheath removal.

Common Side Effects:

• Bleeding (access site, gastrointestinal, urogenital)
• Back pain
• Headache
• Hypotension
• Nausea

Serious Side Effects:

• Intracranial hemorrhage
• Gastrointestinal hemorrhage
• Retroperitoneal bleeding
• Anaphylactic reactions
• Thrombocytopenia (rare)

Timing:
Bleeding complications may occur during or within hours post-PCI.

• Antiplatelets (e.g., Aspirin, Clopidogrel):
  Additive risk of bleeding.
• Thrombolytics (e.g., Alteplase):
  Increased hemorrhagic risk.
• Other Anticoagulants (e.g., Heparin, Warfarin):
  Concurrent use not recommended.
• No significant CYP450 interactions:
  Bivalirudin is not metabolized by liver enzymes.

• 2023 AHA/ACC Guidelines:
  Continue recommending Bivalirudin as an alternative to heparin in patients with high bleeding risk or HIT.
• Regulatory Updates:
  Reinforcement of renal dosing adjustments in package inserts for improved safety.

• Powder for Reconstitution:
  Store at 2°C to 8°C (refrigerated).
• After Reconstitution:
• Stable for up to 24 hours at 2°C to 8°C.
• Protect from light and avoid freezing.
• Use aseptic technique; discard unused solution.