Bivalirudin is indicated for:

• Use as an anticoagulant in patients undergoing PTCA/PCI, including those with HIT or HITTS.
• Management of unstable angina or non–ST-elevation myocardial infarction (off-label).
• Patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI (off-label).
• Treatment of heparin-induced thrombocytopenia.

Bivalirudin is a direct thrombin inhibitor that binds specifically to both the catalytic active site and the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a key enzyme in coagulation, responsible for converting fibrinogen to fibrin and activating Factor XIII to XIIIa, which stabilizes the clot. It also activates Factors V and VIII, enhancing further thrombin production, and stimulates platelet activation and aggregation.

The interaction between bivalirudin and thrombin is reversible, as thrombin gradually cleaves the bivalirudin molecule, restoring thrombin’s functional activity. In vitro studies show that bivalirudin inhibits both free and clot-associated thrombin, is not neutralized by platelet release products, and prolongs coagulation parameters such as activated partial thromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) in a dose-dependent manner. The clinical significance of these laboratory findings remains uncertain.

PCI/PTCA: IV Bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for duration of PCI procedure. Five minutes after bolus dose, obtain ACT and administer additional bolus of 0.3 mg/kg if indicated.

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

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

Concomitant Therapy: Bivalirudin is intended for concurrent use with aspirin (300 to 325 mg/day).

Renal Function Impairment:

• CrCl 30 to 50 mL/min: Administer infusion at rate of 1.75 mg/kg/h.
• CrCl less than 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.

Administration

• For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
• Reconstitute powder for injection with 5 mL sterile water for injection. Gently swirl until powder is dissolved.
• For initial bolus infusion, further dilute each reconstituted vial in 50 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 5 mg/mL.
• For low rate infusion, further dilute each reconstituted vial in 500 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 0.5 mg/mL.
• Do not mix with the following drugs in the same IV line: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, dobutamine, prochlorperazine, reteplase, streptokinase, vancomycin.
• Reconstituted bivalirudin should be a clear to slightly opalescent, colorless to slightly yellow solution. Do not administer if reconstituted or diluted solution is discolored, cloudy, or contains particulate matter.
• Maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.
• Discard any unused reconstituted or diluted solution.

Concurrent administration of bivalirudin with heparin, warfarin, thrombolytic agents, or GP IIb/IIIa inhibitors may increase the risk of significant bleeding.

Bivalirudin is contraindicated in patients with active major bleeding or in those with known hypersensitivity (e.g., anaphylaxis) to bivalirudin or any of its components.

• General: Fever, infection, sepsis.
• Cardiovascular: Hypotension, syncope, vascular abnormalities, ventricular fibrillation.
• Nervous system: Cerebral ischemia, confusion, facial paralysis.
• Respiratory: Pulmonary edema.
• Urogenital: Renal failure, oliguria.

Pregnancy (Category B): Adequate and well-controlled studies in pregnant women are lacking. As animal studies may not fully predict human response, bivalirudin should be used during pregnancy only if clearly necessary. It is intended for short-term use. There is a potential risk of increased maternal bleeding, particularly during the third trimester. Use with aspirin during pregnancy only if essential.

Nursing Mothers: It is unknown whether bivalirudin is excreted in human milk. Caution is advised when administering to breastfeeding women.

Bleeding risk: Although bleeding commonly occurs at arterial puncture sites during PCI/PTCA, hemorrhage may occur at any location. Unexplained drops in blood pressure or hematocrit may indicate bleeding and require discontinuation of therapy. Use cautiously in patients at increased risk of bleeding.

Coronary artery brachytherapy: Increased risk of thrombus formation, including fatal outcomes, has been reported. If used during such procedures, careful catheter management and prevention of blood stasis are essential.

Renal impairment: Clearance of bivalirudin decreases in patients with renal dysfunction; dose adjustment and careful monitoring are required.
Hemodialysis: Reduce infusion dose to 0.25 mg/kg/h; no adjustment of bolus dose needed.
Pediatric use: Safety and effectiveness have not been established.
Geriatric use: Elderly patients may experience a higher incidence of bleeding compared to younger patients.

Overdose cases (up to 10 times the recommended dose) have been reported. Most were related to failure in dose adjustment, especially in renal impairment. Bleeding, including fatal hemorrhage, may occur. In suspected overdose, discontinue bivalirudin immediately and monitor closely. There is no specific antidote, but bivalirudin can be removed by hemodialysis.

Antiplatelet agents.

Store below 30°C in a dry place. Do not freeze. Keep out of reach of children.