Biva IV Injection

Biva 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

Bivalirudin directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding 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; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. 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, was not neutralized by products of the platelet release reaction, and prolonged the activated partialthromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) of normal human plasma in a concentration-dependent manner. The clinical relevance of these findings is unknown.

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.

• 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 via 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.

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

Bivalirudin is contraindicated in patients with: Active major
bleeding & Hypersensitivity (e.g., anaphylaxis) to Bivalirudin or its components

• Bleeding, Body as a Whole: fever,infection, sepsis;
• Cardiovascular: hypotension, syncope, vascular anomaly,ventricular fibrillation;
• Nervous: cerebral ischemia, confusion, facialparalysis;
• Respiratory: lung edema;
• Urogenital: kidney failure, oliguria.

Pregnancy Category B. No adequate and well-controlled studies in pregnant women. As animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Bivalirudin is intended for use with aspirin . Because of possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Bivalirudin and aspirin should be used together during pregnancy only if clearly needed.

Nursing Mothers: It is not known whether bivalirudin is excreted in human milk. As many drugs are excreted in human milk, caution should be exercised when Bivalirudin is administered to a nursing woman.

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 disease states associated with an increased risk of bleeding.

Coronary Artery Brachy therapy: 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, maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.

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

Hemodialysis: Reduce infusion rate to 0.25 mg/kg/h. No reduction in bolus dose needed.

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.

Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of Biva have been reported in clinical trials and in postmarketing reports. A number of the reported overdoses were due to failure to adjust the infusion dose of Biva in persons with renal dysfunction including persons on hemodialysis . Bleeding, as well as deaths due to hemorrhage, have been observed in some reports of overdose. In cases of suspected overdosage, discontinue Biva immediately and monitor the patient closely for signs of bleeding. There is no known antidote to Biva. Biva is hemodialyzable

Anti-platelet drugs

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

Store at temperature not exceeding 30º C in a dry place. Do not freeze. Keep out of reach of children