Bivalirudin is indicated for:

● Anticoagulant in patients undergoing PTCA/PCI or PCI with HITS/HITTS
● Unstable angina/non-ST-elevation MI (Off-label)
● STEMI undergoing primary PCI (Off-label)
● Heparin-induced thrombocytopenia

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

HIT/HITTS (Adults): Administer an 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 (Adults): IV infusion may be continued for up to 4 hours post-procedure, as indicated. After 4 hours, an additional IV infusion of 0.2 mg/kg/h for up to 20 hours may be given if needed.

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

Renal Function Impairment (Adults):
Ccr 30 to 50 mL/min: Administer infusion at a rate of 1.75 mg/kg/h.
Ccr less than 30 mL/min: Reduce the infusion rate to 1 mg/kg/h.
Hemodialysis: Reduce the infusion rate to 0.25 mg/kg/h. No reduction in bolus dose is needed.

General Advice

● For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
● Reconstitute the powder for injection with 5 mL of sterile water for injection. Gently swirl until the powder is dissolved.
● For the 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 the 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.

Bleeding
Body as a whole: Fever, infection, sepsis
Cardiovascular: Hypotension, syncope, vascular anomaly, ventricular fibrillation
Nervous system: Cerebral ischemia, confusion, facial paralysis
Respiratory: Lung edema
Urogenital: Kidney failure, oliguria

Biva® is contraindicated in patients with:

Active major bleeding
Hypersensitivity (e.g., anaphylaxis) to Biva® or its components

Bleeding Events

Although most bleeding associated with the use of Biva® in PCI/PTCA occurs at the site of arterial puncture, hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of Biva® administration. Biva® should be used with caution in patients with conditions associated with an increased risk of bleeding.

Coronary Artery Brachytherapy

An increased risk of thrombus formation, including fatal outcomes, has been associated with the use of Biva® in gamma brachytherapy. If a decision is made to use Biva® during brachytherapy procedures, meticulous catheter technique should be maintained, with frequent aspiration and flushing to minimize conditions of stasis within the catheter or vessels.

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Since animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Biva® is intended for use with aspirin. Due to possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Biva® and aspirin should be used together during pregnancy only if clearly necessary.

Nursing Mothers: It is not known whether bivalirudin is excreted in human milk. Since many drugs are excreted in human milk, caution should be exercised when administering Biva® to a nursing woman.

Pediatric Use: The safety and effectiveness of Biva® in pediatric patients have not been established.

Geriatric Use: Elderly patients experienced more bleeding events than younger patients. Patients treated with Biva® experienced fewer bleeding events in each age stratum compared to heparin.

Renal Impairment: The clearance of Biva® was reduced by approximately 20% in patients with moderate and severe renal impairment and by approximately 80% in dialysis-dependent patients. The infusion dose of Biva® may need to be reduced, and anticoagulant status should be monitored in patients with renal impairment.

Co-administration of Biva® with heparin, warfarin, thrombolytics, or GPIs was associated with an increased risk of major bleeding events.

Cases of overdose up to 10 times the recommended bolus or continuous infusion dose of Biva® have been reported in clinical trials and post-marketing reports. Several overdoses resulted from a failure to adjust the infusion dose in patients with renal dysfunction, including those on hemodialysis. Bleeding and deaths due to hemorrhage have been observed in some overdose cases. If overdose is suspected, discontinue Biva® immediately and closely monitor the patient for signs of bleeding. There is no known antidote for Biva®. Biva® is hemodialyzable.

Store at a temperature not exceeding 30ºC in a dry place. Do not freeze.

Storage after Reconstitution
Do not freeze reconstituted or diluted Biva®.
Reconstituted material may be stored at 2-8ºC for up to 24 hours.
Diluted Biva® with a concentration between 0.5 mg/mL and 5 mg/mL is stable at room temperature for up to 24 hours.
Discard any unused portion of the reconstituted solution remaining in the vial.

Biva® 250: Each box contains one vial with Bivalirudin INN 250 mg and 5 mL of sterile water for injection.

Medicine: Keep out of reach of children.