DrugindexOnline^{2nd edition}

Pronouncation: (bye-VAL-ih-ruh-din)
Class: Thrombin inhibitor

Trade Names:
Angiomax
- Powder for injection, lyophilized 250 mg

Mechanism of Action

Pharmacology

Inhibits thrombin by reversibly binding to the catalytic site and the anion-binding exosite of circulating and clot-bound thrombin.

Pharmacokinetics

Absorption

Steady-state concentration is about 12.3 mcg/mL.

Distribution

Not bound to plasma proteins (other than thrombin) or red blood cells.

Elimination

Cleared from plasma by renal mechanisms and proteolytic cleavage; elimination related to glomerular filtration rate. The t _½ is 25 min. Cl is 3.4 mL/min/kg.

Onset

Produces immediate anticoagulant effect.

Duration

Coagulation times return to baseline about 1 h following end of administration.

Special Populations

Renal Function Impairment

Cl is reduced about 20% in moderate to severe renal function impairment and about 80% in dialysis-dependent patients.

Indications and Usage

Anticoagulant in combination with aspirin in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA); anticoagulant in combination with aspirin and provisional use of glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor in patients undergoing percutaneous coronary intervention (PCI); in combination with aspirin for treatment of patients with, or at risk of heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI.

Contraindications

Active major bleeding, hypersensitivity to bivalirudin.

Dosage and Administration

PCI/PCTA
Adults

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
Adults

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 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
Adults

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

Renal Function Impairment
Adults

IV Ccr 30 to 50 mL/min: Administer infusion at rate of 1.75 mg/kg/h. Ccr 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.

General Advice

• 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.

Storage/Stability

Store unopened vials at controlled room temperature (59° to 86°F). Refrigerate reconstituted solution up to 24 h (36° to 46°F). Diluted solution may be stored for up to 24 h at controlled room temperature. Protect reconstituted solutions from freezing.

Drug Interactions

Glycoprotein IIb/IIIa inhibitors, heparin, thrombolytics, warfarin

The risk of major bleeding may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (12%); hypertension (6%); bradycardia (5%); thrombus formation during PCI with and without intracoronary brachytherapy (postmarketing).

CNS

Headache (12%); insomnia (7%); anxiety (6%); nervousness (5%).

GI

Nausea (15%); vomiting (6%); abdominal pain, dyspepsia (5%).

Genitourinary

Urinary retention (4%).

Hematologic

Major hemorrhage (4%); fatal bleeding (postmarketing).

Miscellaneous

Back pain (42%); pain (15%); injection site pain (8%); pelvic pain (6%); fever (5%); hypersensitivity and allergic reactions including rare reports of anaphylaxis (postmarketing).

Precautions

Monitor Monitor patient for signs of bleeding throughout therapy.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

More bleeding events reported in elderly patients than younger patients.

Special Risk Patients

Use with caution in patients with disease states associated with an increased risk of bleeding.

Brachytherapy

Use with caution; increased risk of thrombus formation has been associated with use of bivalirudin as the antithrombin in gamma brachytherapy.

Hemorrhage

May occur at any site. Avoid IM injections of other medications. Venipuncture sites may require pressure to prevent bleeding and hematoma formation. Consider hemorrhagic event if unexplained fall in hematocrit or BP, or any unexplained symptom is noted.

Immunogenicity

Treatment-emergent positive antibody tests may occur.

Overdosage

Symptoms

Adverse reactions have not been reported; however, monitor for signs of bleeding.

Patient Information

• Advise patient that medication will be prepared and administered by health care provider before PTCA is attempted and for several hours after the procedure.
• Instruct patient to inform health care provider if any of the following symptoms are noted during the administration of drug: back pain, bleeding, headache, nausea, pain, pain at the injection site.