Biva250 mg/5 ml

Biva is a direct thrombin inhibitor anticoagulant with the following evidence-based uses:

FDA-approved / established uses

• Anticoagulation in patients undergoing percutaneous coronary intervention (PCI), including primary PCI for acute coronary syndromes, used with provisional glycoprotein IIb/IIIa inhibition.
• Anticoagulation in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA).
• Anticoagulation in patients with, or at risk of, heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) who require PCI, as an alternative to heparin.

Guideline-supported / adjunct use

• Cardiology society guidelines list Biva as an acceptable procedural anticoagulant option during PCI, particularly when heparin is contraindicated or bleeding risk is a concern.

Off-label use

• Biva is used off-label in select patients with confirmed or suspected HIT who require systemic anticoagulation outside the catheterization laboratory (e.g., during cardiopulmonary bypass or extracorporeal circuits), under specialist supervision; this is not an FDA-approved indication.

Biva is administered only intravenously in a monitored hospital or catheterization-laboratory setting.

Each vial contains Bivalirudin as the sole active ingredient, supplied as a sterile, preservative-free lyophilized powder for reconstitution and intravenous infusion. Strength is expressed per vial (commonly 250 mg Bivalirudin per vial); no other active pharmaceutical ingredient is present.

Biva is a synthetic, bivalent direct thrombin inhibitor derived structurally from hirudin. Unlike heparin, Biva does not require antithrombin as a cofactor and provides predictable, reversible anticoagulation with a short half-life. Biva is given only by the intravenous route and is used specifically during coronary interventional procedures where rapid-onset, tightly controlled anticoagulation is required.

Biva is supplied as a lyophilized powder that must be reconstituted and further diluted before intravenous bolus and infusion administration.

Anticoagulant - Direct Thrombin Inhibitor (bivalent hirudin analogue). Biva belongs to this class.

Bivalirudin is a 20-amino-acid synthetic peptide that acts as a specific and reversible direct thrombin inhibitor. Bivalirudin binds directly to both the catalytic (active) site and the anion-binding exosite I of thrombin, thereby inhibiting thrombin's ability to convert fibrinogen to fibrin, regardless of whether the thrombin is free (fluid-phase) or bound within a formed clot.

Unlike hirudin, the binding of Bivalirudin to thrombin is transient: thrombin itself slowly cleaves the bivalirudin molecule, gradually restoring thrombin's active site over time. This gives Bivalirudin a predictable onset/offset profile and a short elimination half-life (approximately 25 minutes in patients with normal renal function), which increases in renal impairment because a portion of elimination is renal (proteolytic cleavage plus renal clearance).

Anticoagulant effect with Bivalirudin is monitored using activated clotting time (ACT) during the procedure.

Biva is administered by intravenous bolus followed by continuous intravenous infusion, using an infusion pump, only in a hospital or cardiac catheterization-laboratory setting by clinicians experienced in interventional cardiology and procedural anticoagulation. Biva must never be given intramuscularly or subcutaneously. Activated clotting time (ACT) is monitored during the infusion to guide additional bolus dosing if needed. Biva is not intended for outpatient or self-administered use.

Because Biva is an anticoagulant, the principal clinically significant interactions increase bleeding risk through additive antihemostatic effects:

• Other anticoagulants (heparin, low-molecular-weight heparins, fondaparinux, warfarin, direct oral anticoagulants) - concurrent use with Biva substantially increases bleeding risk; dosing is managed per specific procedural protocol.
• Antiplatelet agents (aspirin, P2Y12 inhibitors such as clopidogrel, and glycoprotein IIb/IIIa inhibitors) - commonly co-administered with Biva during PCI but increase bleeding risk; requires close monitoring per institutional protocol.
• Thrombolytic agents - increased risk of serious bleeding, including intracranial hemorrhage, when combined with Biva.
• NSAIDs - may add to bleeding risk when used with Biva due to effects on platelet function.

No clinically significant pharmacokinetic (metabolic) drug interactions have been established for Biva, as it is cleared primarily by proteolytic cleavage and renal elimination rather than hepatic enzyme metabolism.

The most significant adverse effect of Biva is bleeding. Other adverse effects reported with Biva include:

Patients receiving Biva should be monitored closely for any signs of bleeding throughout and after the procedure.

Pregnancy: Animal reproduction studies with Biva have not demonstrated clear evidence of fetal harm, but there are no adequate and well-controlled studies in pregnant women. Biva should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; use only under direct physician supervision, which is inherent to how Biva is administered.

Lactation: It is not known whether Biva is excreted in human milk. Because Biva is used only as a short intravenous infusion in an acute hospital setting, a decision regarding breastfeeding should be made by the treating physician weighing the clinical situation; consult a physician before breastfeeding after receiving Biva.

Bleeding risk: Bleeding is the most common and most significant risk with Biva. Monitor closely for signs of bleeding during and after the procedure, including access-site bleeding, gastrointestinal bleeding, and intracranial hemorrhage.

Renal impairment: Biva is partly renally eliminated; significant renal impairment increases bleeding risk due to reduced clearance. Dose reduction is required in severe renal impairment and in dialysis-dependent patients (see Dosage and Administration).

Hepatic impairment: Use Biva with caution, as clinical experience is limited.

Hospital/specialist use only: Biva is used only in a monitored hospital or catheterization-laboratory setting by clinicians experienced in interventional cardiology and anticoagulation management; it is not an outpatient or self-administered medication.

Concurrent anticoagulant/antiplatelet therapy: Concurrent use of Biva with other anticoagulants or antiplatelet agents increases bleeding risk and is managed per specific procedural anticoagulation protocols (see Drug Interactions).

Thrombosis and stent thrombosis: Thrombosis, including catheter thrombosis and acute stent thrombosis, has been reported with inadequate dosing of Biva in certain contexts. Dosing and ACT monitoring per specific procedural protocol is essential while using Biva.

Spinal/epidural procedures: Use of Biva in patients undergoing spinal or epidural anesthesia/puncture carries a risk of epidural or spinal hematoma resulting in long-term paralysis; this combination should be avoided unless deemed necessary by the treating physician.

Overdose of Biva may present primarily as bleeding (minor or major, including at access sites, gastrointestinal tract, or intracranially). There is no specific antidote or reversal agent for Biva. Because Biva has a short half-life and is given as a hospital-monitored infusion, suspected overdose should be managed by immediately stopping or reducing the infusion and seeking immediate medical attention; the treating team may provide supportive care, local hemostatic measures, and transfusion support as clinically indicated. Biva is not removed to a clinically important extent by hemodialysis at standard dialysis flow rates, though data are limited. Patients or caregivers who suspect an overdose should contact emergency services or poison control immediately.

Store unreconstituted Biva vials refrigerated at 2°C to 8°C (36°F to 46°F), protected from light. After reconstitution and dilution, solutions of Biva may be stored at room temperature (up to 30°C) for up to 24 hours. Keep out of reach of children. Do not use beyond the labeled expiry date.

Renal impairment: Dose reduction of Biva is required in severe renal impairment and dialysis-dependent patients (see Dosage and Administration).

Hepatic impairment: Use Biva with caution; specific dose adjustment has not been established.

Elderly: No specific dose adjustment of Biva is required based on age alone, but elderly patients often have reduced renal function, so renal status should guide dosing.

Pediatric patients: Safety and efficacy of Biva in pediatric patients have not been established.

Pregnancy and lactation: See Pregnancy and Lactation section.

Biva is administered only for the duration of the percutaneous coronary intervention procedure, typically 30 minutes to a few hours. At the treating physician's discretion, the infusion of Biva may be continued for up to 4 hours post-procedure, and in select cases a reduced-dose infusion may continue for up to a further 20 hours if ongoing anticoagulation is clinically indicated. Biva is not intended for long-term or outpatient use.

Biva is supplied as a lyophilized powder that must be reconstituted before use. Add sterile water for injection to the vial to fully dissolve the powder, then further dilute the reconstituted Biva solution in 5% dextrose in water or 0.9% sodium chloride injection to the required concentration before intravenous bolus and infusion administration, following the specific volume instructions provided with the product. Reconstitution and dilution of Biva should be performed by trained healthcare personnel using aseptic technique.

Anticoagulants; Direct thrombin inhibitors (bivalent). Bivalirudin is classified within this drug class.

Bivalirudin is a specific, reversible direct thrombin inhibitor that binds simultaneously to the catalytic site and the anion-binding exosite I of both circulating (fluid-phase) and clot-bound thrombin, blocking thrombin-mediated conversion of fibrinogen to fibrin. The binding of Bivalirudin is reversible because thrombin itself slowly cleaves the bound peptide, restoring thrombin activity over time, which distinguishes Bivalirudin from irreversible thrombin inhibitors such as hirudin.

B

Safety and efficacy of Biva in pediatric patients have not been established in adequate controlled studies. Use of Biva in children should occur only in specialized settings under close specialist supervision when no suitable alternative exists, with dosing individualized and extrapolated cautiously from adult data.