Bivalirudin: Pediatric drug information

For additional information see "Bivalirudin: Drug information" and "Bivalirudin: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Angiomax;
Bivalirudin RTU [DSC]

Brand Names: Canada

Angiomax

Therapeutic Category

Anticoagulant;
Anticoagulant, Direct Thrombin Inhibitor

Dosing: Neonatal

Dosage guidance:

Clinical considerations: Bivalirudin is an alternative treatment option to heparin; reserve for use in patients with heparin resistance or evidence of significant thrombosis while on heparin (Ref). Use in heparin-induced thrombocytopenia (HIT) has been described in adult and pediatric patients; however, dosing recommendations are limited (Ref). Measure baseline aPTT and kidney function prior to initiation.

Anticoagulation, mechanical circulatory support

Anticoagulation, mechanical circulatory support:

Extracorporeal membrane oxygenation [ECMO]/extracorporeal life support [ECLS] (Ref): Very limited data available:

Note: Determine patient's kidney function prior to initiating therapy; dosage adjustment recommended in cases of kidney impairment (CrCl ≤60 mL/minute/1.73 m²); goal aPTT range determined by risk of bleeding and thrombosis and postoperative phase of care.

Neonates:

Initial dose: Continuous IV infusion: 0.15 to 0.3 mg/kg/hour; reported initial range: 0.05 to 0.3 mg/kg/hour. Note: Some experts recommend a lower initial dose of 0.2 mg/kg/hour in patients with open sternotomy. Measure aPTT 2 to 4 hours after initiation and titrate to achieve goal aPTT.

Dose adjustment: Continuous IV infusion: One published approach to dose adjustment presented in the table; refer to institutional protocols.

**Bivalirudin ECMO/ECLS in Neonates: Dose Adjustments to Achieve Target aPTT**
aPTT	Bivalirudin titration	Time to repeat aPTT^a
^a Consider more frequent aPTT monitoring based on clinical scenario.
Adapted from Seelhammer 2021.
>20 seconds below goal range	Increase infusion rate by 20%	2 hours
10 to 20 seconds below goal range	Increase infusion rate by 10%	2 hours
Within goal range	No change	12 hours; decrease frequency based on clinical scenario
10 to 20 seconds above goal range	Decrease infusion rate by 10%	2 hours
>20 seconds above goal range	Hold for 1 hour then decrease infusion rate by 20%	2 hours

Ventricular assist device (VAD) (Ref): Very limited data available:

Note: Dosing based on a consensus protocol; determine patient's kidney function prior to initiating therapy; dosage adjustment recommended in cases of kidney impairment (GFR ≤60 mL/minute/1.73 m²); goal aPTT range determined by risk of bleeding and thrombosis and postoperative phase of care.

Neonates:

Initial dose: Continuous IV infusion: 0.3 mg/kg/hour. Measure aPTT 2 hours after initiation; use caution when titrating after first aPTT and adjust as follows:

**Bivalirudin VAD in Neonates: First Dose Adjustment After Initiation**
aPTT	Bivalirudin titration	Time to repeat aPTT
Adapted from ACTION 2023.
1 to 1.5 × baseline	No change	2 to 3 hours
>2 to 3 × baseline	Decrease infusion rate by 50%	2 to 3 hours

Maintenance dose: Continuous IV infusion: After first aPTT measurement and adjustment, measure aPTT in 2 to 3 hours and adjust as follows:

**Bivalirudin VAD in Neonates: Maintenance Dose Adjustments to Achieve Target aPTT**
aPTT	Bivalirudin titration	Time to repeat aPTT^a
^a Consider more frequent aPTT monitoring based on clinical scenario. ^b Round dose up to closest second decimal (hundredth place). ^c Recommendation in patient with normal kidney function; dose adjustment required for all levels of kidney impairment; see recommendations for mild to moderate and severe kidney impairment. Adapted from ACTION 2023.
≥15 to 30 seconds below target range	Increase infusion rate by 25%^b	2 to 3 hours
5 to <15 seconds below target range	Increase infusion rate by 15%^b	2 to 3 hours
Within goal range	No change	2 to 3 hours; decrease frequency based on clinical scenario
5 to <15 seconds above target range	Decrease infusion rate by 15%^b	2 to 3 hours
≥15 to 30 seconds above target range	Decrease infusion rate by 25%^b	2 to 3 hours
>3 × baseline or ~120 seconds	Hold infusion for 15 minutes then decrease infusion rate by 30%^b,c	2 to 3 hours

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures: Very limited data available:

Note: Determine patient's kidney function prior to initiating therapy; dosage adjustment recommended in cases of kidney impairment (GFR <30 mL/minute/1.73 m²) (Ref).

Neonates weighing ≥2.5 kg: IV bolus (prior to catheterization): 0.75 mg/kg once followed by continuous IV infusion of 1.75 mg/kg/hour, titrated to goal activated clotting time (ACT) (Ref).

Thrombosis, treatment

Thrombosis (not associated with mechanical circulatory support), treatment: Very limited data available:

Note: Goal aPTT range determined by risk of bleeding. Dosing based on 2 retrospective reviews that included 8 neonates (Ref).

Neonates: GA >35 weeks:

Bolus dose (optional): IV: Reported range: 0.125 to 0.25 mg/kg once; Note: A higher dose of 0.5 mg/kg was reported in one patient.

Continuous IV infusion: Initial: 0.05 to 0.25 mg/kg/hour; titrate to achieve target aPTT; reported average dose range: 0.06 to 0.31 mg/kg/hour; maximum reported dose: 0.4 mg/kg/hour.

Dosing: Altered kidney function: Neonatal:

ECMO/ECLS:

Baseline kidney impairment:

Initial dosing (Ref): Based on an initial dose of 0.15 mg/kg/hour:

CrCl >60 mL/minute/1.73 m²: No dosage adjustment necessary.

CrCl 30 to 60 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.1 mg/kg/hour.

CrCl 10 to 29 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.07 mg/kg/hour.

CrCl <10 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.02 mg/kg/hour.

Continuous renal replacement therapy (CRRT): Continuous IV infusion: Initial: Decrease initial dose to 0.04 mg/kg/hour.

VAD:

Baseline kidney impairment: Note: Measure baseline aPTT prior to initiation (Ref):

Initial dosing (Ref):

Mild to moderate impairment (GFR 30 to 60 mL/minute/1.73 m²): Continuous IV infusion: Initial: Decrease initial dose to 0.2 mg/kg/hour; measure aPTT 2 hours after initiation and titrate cautiously with first aPTT measurement; see "Bivalirudin VAD in Neonates: First Dose Adjustment After Initiation" table and "Bivalirudin VAD in Neonates: Maintenance Dosage Adjustments to Achieve Target aPTT" table for details.

Severe impairment (GFR <30 mL/minute/1.73 m²): Continuous IV infusion: Initial: Decrease initial dose to 0.1 mg/kg/hour; measure aPTT 2 hours after initiation and titrate cautiously with first aPTT measurement; see "Bivalirudin VAD in Neonates: First Dose Adjustment After Initiation" table and "Bivalirudin VAD in Neonates: Maintenance Dosage Adjustments to Achieve Target aPTT" table for details.

Kidney impairment during therapy (Ref):

Dosage adjustments for aPTT >3 times baseline or ~120 seconds:

Mild to moderate impairment (GFR 30 to 60 mL/minute/1.73 m²): Continuous IV infusion: Hold infusion for 45 minutes then decrease infusion rate by 40%.

Severe impairment (GFR <30 mL/minute/1.73 m²): Continuous IV infusion: Hold infusion for 2 hours then recheck aPTT before restarting.

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures:

Baseline kidney impairment:

Neonates weighing ≥2.5 kg: GFR <30 mL/minute/1.73 m²: Continuous IV infusion: Decrease initial dose to 1 mg/kg/hour, titrate to goal ACT (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Pediatric

Dosage guidance:

Anticoagulation, mechanical circulatory support

Anticoagulation, mechanical circulatory support:

Cardiopulmonary bypass (CPB) (Ref): Very limited data available:

Children:

CPB circuit prime: IV: 50 mg once added to pump prime.

Bolus: Initial: IV bolus: 1 mg/kg followed by continuous IV infusion at 2.5 mg/kg/hour; check activated clotting time (ACT) in 5 minutes; if ACT <480 seconds, repeat IV bolus of 0.25 mg/kg and increase continuous IV infusion by 1.25 mg/kg/hour; titrate to goal ACT >480 seconds. Dosing based on one prospective, randomized controlled trial (n=24) in which the mean IV bolus dose required was 1.7 ± 0.2 mg/kg and the mean continuous IV infusion required was 3 ± 0.7 mg/kg/hour.

Extracorporeal membrane oxygenation [ECMO]/extracorporeal life support [ECLS] (Ref): Limited data available:

Infants, Children, and Adolescents:

Initial dose: Continuous IV infusion: Initial: 0.15 to 0.3 mg/kg/hour; reported initial range: 0.05 to 0.3 mg/kg/hour. Note: Some experts recommend a lower initial dose of 0.2 mg/kg/hour in patients with open sternotomy. Measure aPTT 2 to 4 hours after initiation and titrate to achieve goal aPTT.

Dose adjustment: Continuous IV infusion: One published approach to dose adjustment presented in the table; refer to institutional protocols.

**Bivalirudin ECMO/ECLS in Infants, Children, and Adolescents: Dose Adjustments to Achieve Target aPTT**
aPTT	Bivalirudin titration	Time to repeat aPTT^a
^a Consider more frequent aPTT monitoring based on clinical scenario.
Adapted from Seelhammer 2021.
>20 seconds below goal range	Increase infusion rate by 20%	2 hours
10 to 20 seconds below goal range	Increase infusion rate by 10%	2 hours
Within goal range	No change	12 hours; decrease frequency based on clinical scenario
10 to 20 seconds above goal range	Decrease infusion rate by 10%	2 hours
>20 seconds above goal range	Hold for 1 hour then decrease infusion rate by 20%	2 hours

Ventricular assist device (VAD) (Ref): Very limited data available:

Infants, Children, and Adolescents:

Initial dose: Continuous IV infusion: Initial: 0.3 mg/kg/hour. Measure aPTT 2 hours after initiation; use caution when titrating after first aPTT and adjust as follows:

**Bivalirudin VAD in Infants, Children, and Adolescents: First Dose Adjustment After Initiation**
aPTT	Bivalirudin titration	Time to repeat aPTT
Adapted from ACTION 2023.
1 to 1.5 × baseline	No adjustment	2 to 3 hours
>2 to 3 × baseline	Decrease infusion rate by 50%	2 to 3 hours

Maintenance dose: Continuous IV infusion: After first aPTT measurement and adjustment, measure aPTT in 2 to 3 hours and adjust as follows:

**Bivalirudin VAD in Infants, Children, and Adolescents: Maintenance Dose Adjustments to Achieve Target aPTT**
aPTT	Bivalirudin titration	Time to repeat aPTT^a
^a Consider more frequent aPTT monitoring based on clinical scenario. ^b Round dose up to closest second decimal (hundredth place). ^c Recommendation in patient with normal kidney function; dose adjustment required for all levels of kidney impairment; see recommendations for mild to moderate and severe kidney impairment. Adapted from ACTION 2023.
≥15 to 30 seconds below target range	Increase infusion rate by 25%^b	2 to 3 hours
5 to <15 seconds below target range	Increase infusion rate by 15%^b	2 to 3 hours
Within goal range	No change	2 to 3 hours; decrease frequency based on clinical scenario
5 to <15 seconds above target range	Decrease infusion rate by 15%^b	2 to 3 hours
≥15 to 30 seconds above target range	Decrease infusion rate by 25%^b	2 to 3 hours
>3 × baseline or ~120 seconds	Hold infusion for 15 minutes then decrease infusion by 30%^b,c	2 to 3 hours

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures: Very limited data available:

Note: Determine patient's kidney function prior to initiating therapy; dosage adjustment recommended in cases of kidney impairment (CrCl <30 mL/minute/1.73 m²) (Ref).

Infants weighing ≥2.5 kg, Children, and Adolescents: IV bolus (prior to catheterization): 0.75 mg/kg once followed by continuous IV infusion of 1.75 mg/kg/hour, titrated to goal ACT. Note: A lower bolus dose of 0.5 mg/kg and maintenance dose of 0.25 mg/kg/hour have also been reported in an infant (Ref).

Thrombosis, treatment

Thrombosis (not associated with mechanical circulatory support), treatment: Very limited data available:

Note: Goal aPTT range determined by risk of bleeding. Dosing based on one retrospective review and one prospective, open-label pilot study (n=20) (Ref).

Infants, Children, and Adolescents:

Bolus dose (optional): IV: Usual initial range: 0.05 to 0.25 mg/kg once; doses up to 0.5 mg/kg have been described.

Continuous IV infusion: Initial: 0.05 to 0.25 mg/kg/hour; titrate to achieve target aPTT; reported average dose range: 0.05 to 0.21 mg/kg/hour; reported maximum dose: 0.3 mg/kg/hour. Higher doses (0.5 and 0.625 mg/kg/hour) were reported; however, significant hematuria occurred in both patients.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Anticoagulation, extracorporeal membrane oxygenation [ECMO]/extracorporeal life support [ECLS]:

Baseline kidney impairment: Based on an initial dose of 0.15 mg/kg/hour:

Initial dosing (Ref):

Infants, Children, and Adolescents:

CrCl >60 mL/minute/1.73 m²: No dosage adjustment necessary.

CrCl 30 to 60 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.1 mg/kg/hour.

CrCl 10 to 29 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.07 mg/kg/hour.

CrCl <10 mL/minute/1.73 m²: Continuous IV infusion: Initial: Decrease initial dose to 0.02 mg/kg/hour.

Continuous renal replacement therapy (CRRT): Continuous IV infusion: Initial: Decrease initial dose to 0.04 mg/kg/hour.

Anticoagulation, ventricular assist device (VAD):

Baseline kidney impairment:

Infants, Children, and Adolescents:

Initial dosing: Note: Measure baseline aPTT prior to initiation (Ref):

Mild to moderate impairment (CrCl 30 to 60 mL/minute/1.73 m²): Continuous IV infusion: Initial: Decrease initial dose to 0.2 mg/kg/hour; measure aPTT 2 hours after initiation and titrate cautiously with first aPTT measurement; see "Bivalirudin VAD in Infants, Children, and Adolescents: First Dose Adjustment After Initiation" table and "Bivalirudin VAD in Infants, Children, and Adolescents: Maintenance Dosage Adjustments to Achieve Target aPTT" table for details.

Severe impairment (CrCl <30 mL/minute/1.73 m²): Continuous IV infusion: Initial: Decrease initial dose to 0.1 mg/kg/hour; measure aPTT 2 hours after initiation and titrate cautiously with first aPTT measurement; see "Bivalirudin VAD in Infants, Children, and Adolescents: First Dose Adjustment After Initiation" table and "Bivalirudin VAD in Infants, Children, and Adolescents: Maintenance Dosage Adjustments to Achieve Target aPTT" table for details.

Kidney impairment during therapy (Ref):

Infants, Children, and Adolescents:

Dosage adjustments for aPTT >3 times baseline or ~120 seconds:

Mild to moderate impairment (GFR 30 to 60 mL/minute/1.73 m²): Continuous IV infusion: Hold infusion for 45 minutes then decrease infusion rate by 40%.

Severe impairment (GFR <30 mL/minute/1.73 m²): Continuous IV infusion: Hold infusion for 2 hours then recheck aPTT before restarting.

Anticoagulation, interventional cardiac catheterization/percutaneous coronary interventional procedures:

Baseline kidney impairment:

Infants weighing ≥2.5 kg, Children, and Adolescents:

GFR <30 mL/minute/1.73 m²: Continuous IV infusion: Decrease initial dose to 1 mg/kg/hour, titrated to goal activated clotting time (ACT) (Ref).

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. In adults, no dosage adjustment necessary (Ref).

Dosing: Adult

(For additional information see "Bivalirudin: Drug information")

Cardiac surgery

Cardiac surgery (alternative to heparin) ( off-label use):

Note: Consider for use in patients with heparin allergy (eg, allergy to pork containing products) or heparin-induced thrombocytopenia (Ref).

IV: Intraoperative:

Off-pump:

Initial bolus: 0.75 mg/kg followed by continuous infusion (Ref).

Maintenance continuous infusion: 1.75 mg/kg/hour to maintain ACT >300 seconds (Ref).

Note: If patient needs to go on-pump, some have recommended an additional 0.25 mg/kg bolus and increasing the infusion rate to 2.5 mg/kg/hour (Ref).

On-pump:

Initial bolus: 1 to 1.25 mg/kg followed by continuous infusion; add 50 mg bolus to priming solution of cardiopulmonary bypass (CPB) circuit (Ref).

Maintenance continuous infusion: 2.5 mg/kg/hour to maintain ACT >2.5 times baseline; if ACT is subtherapeutic may administer an additional bolus of 0.1 to 0.5 mg/kg and increase infusion by 0.25 mg/kg/hour. Discontinue infusion 10 to 15 minutes prior to weaning from CPB (Ref). Note: Special maneuvers are needed to prevent stasis and clotting within the CPB circuit during and after surgery. When weaning from CPB, may keep blood recirculating through the circuit and administer 50 mg into the CPB circuit followed by a continuous infusion of 50 mg/hour into the CPB circuit; continue infusion until it is evident the patient will not require an urgent return to CPB. If separation from circuit does not occur within 20 minutes of stopping infusion, redose patient with 0.5 mg/kg and restart infusion at 2.5 mg/kg/hour (Ref).

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) (off-label use):

IV: Initial dose: 0.15 to 0.2 mg/kg/hour; adjust to aPTT 1.5 to 2.5 times baseline value (Ref).

Transitioning from bivalirudin to an oral anticoagulant:

Transitioning from bivalirudin to warfarin: Start warfarin and continue bivalirudin until INR is within therapeutic range; overlap bivalirudin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart and for a minimum of 5 days; recheck INR after effect of bivalirudin has dissipated (Ref).

Transitioning from bivalirudin to a direct-acting oral anticoagulant: Start direct-acting oral anticoagulant when bivalirudin infusion is stopped (consult local protocol if the aPTT is above the target range) (Ref).

Ischemic heart disease, percutaneous coronary intervention

Ischemic heart disease, percutaneous coronary intervention (alternative agent):

Note: Includes patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome or when PCI is chosen for stable ischemic heart disease. Consider for use as an alternative to heparin. Use in combination with an appropriate antithrombotic regimen. If unfractionated heparin is initiated then switched to bivalirudin prior to PCI, discontinue unfractionated heparin and wait 30 minutes before starting bivalirudin (Ref).

IV:

If initiating bivalirudin during PCI: Initial: 0.75 mg/kg bolus immediately prior to procedure, followed immediately by 1.75 mg/kg/hour for the duration of procedure. After the procedure, may continue the infusion at 1.75 mg/kg/hour for up to 4 hours (Ref).

If initiating bivalirudin prior to PCI or diagnostic angiography (off-label): Initial: 0.1 mg/kg bolus, followed by 0.25 mg/kg/hour; continue until diagnostic angiography or PCI. If PCI is necessary, give an additional bolus of 0.5 mg/kg and increase infusion to 1.75 mg/kg/hour during PCI (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Percutaneous coronary intervention: IV: Note: CrCl may be estimated using the Cockcroft-Gault equation (Ref). Recommendations are only applicable if initiating bivalirudin during percutaneous coronary intervention.

Bolus: No dosage adjustment necessary.

Continuous infusion:

CrCl ≥30 mL/minute: 1.75 mg/kg/hour.

CrCl <30 mL/minute: 1 mg/kg/hour.

Hemodialysis, intermittent (thrice weekly): Dialyzable (25%): 0.25 mg/kg/hour.

Heparin-induced thrombocytopenia (off-label use):

IV: Note: Initial continuous infusion doses based on estimated CrCl using Cockcroft Gault. Dosing is derived from the results of retrospective, observational data from single-center studies. For higher targets or urgent need to more rapidly achieve therapeutic levels, it may be appropriate to choose a starting dose at the higher end of the recommended ranges. Refer to institution-specific protocols for titration.

CrCl >60 mL/minute: No dosage adjustment necessary; however, based on observational data, a range of 0.13 to 0.16 mg/kg/hour may achieve a target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

CrCl 30 to 60 mL/minute: Initial: 0.08 to 0.12 mg/kg/hour; titrate to achieve target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

CrCl <30 mL/minute: Initial: 0.04 to 0.07 mg/kg/hour; titrate to achieve target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (25% over 4 hours): Initial: 0.04 to 0.08 mg/kg/hour; titrate to achieve target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: IV: Initial: 0.03 to 0.07 mg/kg/hour; titrate to achieve target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

Prolonged intermittent renal replacement therapy (eg, sustained low-efficiency diafiltration): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.

Prolonged intermittent renal replacement therapy (6- to 8-hour session, 6 days per week): IV: Initial: 0.09 mg/kg/hour; titrate to achieve target aPTT of 1.5 to 2.5 times patient baseline or normal range (Ref).

Dosing: Liver Impairment: Adult

No dosage adjustment necessary (Seybert 2006). In patients treated for HIT (off-label use), patients with hepatic impairment required slightly lower doses compared to previous reports for patients with normal hepatic function; however, the lower doses may have been required due to critical illness instead of hepatic impairment (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

1% to 10%:

Cardiovascular: Thrombosis (acute stent thrombosis [<4 hours] in patients with STEMI undergoing primary PCI: 1%)

Hematologic & oncologic: Hemorrhage (including intracranial hemorrhage, major hemorrhage, and retroperitoneal hemorrhage: 4%)

<1%: Immunologic: Antibody development

Frequency not defined:

Hematologic & oncologic: Major hemorrhage, retroperitoneal hemorrhage

Nervous system: Intracranial hemorrhage

Postmarketing:

Cardiovascular: Cardiac tamponade, coronary thrombosis (during PCI, including intracoronary brachytherapy)

Hematologic & oncologic: Increased INR, pulmonary hemorrhage

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Contraindications

Hypersensitivity (eg, anaphylaxis) to bivalirudin or any component of the formulation; active major bleeding.

Canadian labeling: Additional contraindications (not in US labeling): Major blood clotting disorders; acute gastric or duodenal ulcer; cerebral hemorrhage; severe cerebrospinal trauma; bacterial endocarditis; severe uncontrolled hypertension; diabetic or hemorrhagic retinopathy; proximal use of spinal/epidural anesthesia

Warnings/Precautions

Concerns related to adverse effects:

• Acute stent thrombosis: In patients with STEMI undergoing PCI, acute stent thrombosis (some fatal) occurring within 4 hours of the procedure was observed at a greater frequency as compared to those treated with heparin. Patients should remain for at least 24 hours in a facility capable of managing ischemic complications; monitor for signs and symptoms consistent with myocardial ischemia.

• Bleeding: The most common complication is bleeding. Certain patients are at increased risk of bleeding; risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; recent puncture of large vessels or organ biopsy; recent CVA, stroke, intracerebral surgery, or other neuraxial procedure; severe uncontrolled hypertension; renal impairment; recent major surgery; recent major bleeding (intracranial, GI, intraocular, or pulmonary). Monitor for signs and symptoms of bleeding.

• Thrombus formation: Increased risk of intracoronary thrombus formation (some fatal, as reported by the manufacturer) has been reported with use in gamma brachytherapy even with the use of higher doses as compared to doses used for beta radiation (Kuchulakanti 2005). If used during brachytherapy, maintain meticulous catheter technique with frequent aspiration and flushing while minimizing conditions of stasis within the catheter or vessels.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage reduction required.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous [preservative free]:

Bivalirudin RTU: 250 mg/50 mL (50 mL [DSC]) [contains polyethylene glycol (macrogol)]

Generic: 250 mg/50 mL (50 mL)

Solution Reconstituted, Intravenous:

Generic: 250 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Angiomax: 250 mg (1 ea)

Generic: 250 mg (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Bivalirudin Trifluoroacetate Intravenous)

250 mg/50 mL (per mL): $1.14

Solution (reconstituted) (Angiomax Intravenous)

250 mg (per each): $1,170.00

Solution (reconstituted) (Bivalirudin Trifluoroacetate Intravenous)

250 mg (per each): $43.39 - $1,137.27

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 250 mg/50 mL (50 mL)

Solution Reconstituted, Intravenous:

Angiomax: 250 mg (1 ea)

Generic: 250 mg (1 ea)

Administration: Pediatric

Parenteral: IV administration only. Vials (lyophilized powder) must be reconstituted and further diluted prior to administration; premixed frozen IV solution (5 mg/mL) is available. After initial bolus dose (when recommended), administer as a continuous IV infusion via an infusion device.

Administration: Adult

IV: For IV administration only. After initial bolus dose (when recommended), administer as a continuous infusion; refer to indication-specific infusion rates in dosing for detailed recommendations.

Storage/Stability

Solution reconstituted, IV: Store unopened vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Following reconstitution, store vials at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Do not freeze. Final dilutions of 5 mg/mL, in D5W or NS, are stable at room temperature for up to 24 hours.

Solution, IV: Store unopened vials at 2°C to 8°C (36°F to 46°F); may be stored at 20°C to 25°C (68°F to 77°F) for up to 72 hours. Avoid excess heat.

Premixed frozen solution: Store at or below -20°C (-4°F). Thawed solution is stable for 24 hours at room temperature (25°C [77°F]) or for 14 days under refrigeration (5°C [41°F]); do not refreeze.

Use

Anticoagulant used in patients undergoing percutaneous coronary intervention (PCI), including those with heparin-induced thrombocytopenia (HIT)/thrombosis syndrome (HITTS) (FDA approved in adults); has also been used as an anticoagulant in mechanical circulatory support (eg, extracorporeal membrane oxygenation, ventricular assist devices) and in the treatment of thrombosis (not associated with mechanical circulatory support).

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (direct thrombin inhibitor) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

National Patient Safety Goals:

The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, renal function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Acalabrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Aducanumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with aducanumab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification

Alemtuzumab: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Alteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid

Anacaulase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Anagrelide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Antidepressants with Antiplatelet Effects: May increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor

Apixaban: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid

Aspirin: May increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor

Bromperidol: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor

Caplacizumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider Therapy Modification

Chloroprocaine (Systemic): Anticoagulants may increase adverse/toxic effects of Chloroprocaine (Systemic). Risk C: Monitor

Cilostazol: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Collagenase (Systemic): Anticoagulants may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor

Dabigatran Etexilate: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid

Dasatinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Deferasirox: Anticoagulants may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor

Defibrotide: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid

Deoxycholic Acid: Anticoagulants may increase adverse/toxic effects of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor

Desirudin: Anticoagulants may increase anticoagulant effects of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider Therapy Modification

Donanemab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with donanemab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification

Edoxaban: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid

Hemin: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid

Herbal Products with Anticoagulant/Antiplatelet Effects: May increase adverse/toxic effects of Anticoagulants. Bleeding may occur. Risk C: Monitor

Ibritumomab Tiuxetan: Anticoagulants may increase adverse/toxic effects of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor

Ibrutinib: Anticoagulants may increase adverse/toxic effects of Ibrutinib. Specifically, the risks of bleeding and hemorrhage may be increased. Risk C: Monitor

Icosapent Ethyl: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Inotersen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Kanamycin: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Lecanemab: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Management: Avoid use of lecanemab in patients who are being treated with an anticoagulant when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification

Limaprost: May increase adverse/toxic effects of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor

Lipid Emulsion (Fish Oil Based): May increase anticoagulant effects of Anticoagulants. Lipid Emulsion (Fish Oil Based) may decrease anticoagulant effects of Anticoagulants. Risk C: Monitor

Mesoglycan: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

MiFEPRIStone: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid

Nintedanib: Anticoagulants may increase adverse/toxic effects of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Nonselective): May increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Topical): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Obinutuzumab: Anticoagulants may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Management: Consider avoiding coadministration of obinutuzumab and anticoagulants, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification

Omacetaxine: Anticoagulants may increase adverse/toxic effects of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid

Omega-3 Fatty Acids: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Oritavancin: May decrease therapeutic effects of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor

Ozagrel: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of ozagrel and anticoagulants if possible. If coadministration is required, use caution, monitor patients closely for signs and symptoms of bleeding, and consider ozagrel or anticoagulant dose reductions. Risk D: Consider Therapy Modification

Pentosan Polysulfate Sodium: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Pirtobrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Protein C Concentrate (Human): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Reteplase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Rivaroxaban: Anticoagulants may increase anticoagulant effects of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid

Salicylates: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Streptokinase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid

Sugammadex: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Sulodexide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Telavancin: May decrease therapeutic effects of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor

Tenecteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid

Therapeutic Antiplatelets: May increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor

Tibolone: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Tipranavir: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Urokinase: May increase anticoagulant effects of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification

Vitamin E (Systemic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Vitamin K Antagonists: Anticoagulants may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

Volanesorsen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor

Vorapaxar: May increase adverse/toxic effects of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid

Zanubrutinib: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor

Pregnancy Considerations

Bivalirudin is used in conjunction with aspirin, which may lead to maternal or fetal adverse effects, especially during the third trimester. Use of parenteral direct thrombin inhibitors in pregnancy should be limited to those women who have severe allergic reactions to heparin, including heparin-induced thrombocytopenia, and who cannot receive danaparoid (Guyatt 2012).

Monitoring Parameters

Obtain baseline PT/INR, aPTT, kidney function tests, and CBC with differential prior to start of therapy. Check aPTT 2 to 4 hours after start of therapy and with any dosage adjustment. Monitor hemoglobin, hematocrit, platelets, and signs and symptoms of bleeding. Monitor kidney function tests as clinically indicated.

Note: Activated clotting time may also be used in clinical settings where aPTT is not utilized (eg, cardiac catheterization lab, operating room).

Thromboelastography (TEG) R-Time of 12 to 30 minutes has been reported as a modality for monitoring response to bivalirudin in extracorporeal life support (Ranucci 2011) and may be valuable in the setting of decreased sensitivity of aPTT monitoring (ie, significant inflammation, hyperfibrinogenemia, elevated factor VIII levels).

Mechanism of Action

Bivalirudin acts as a specific and reversible direct thrombin inhibitor; it binds to the catalytic and anionic exosite of both circulating and clot-bound thrombin. Catalytic binding site occupation functionally inhibits coagulant effects by preventing thrombin-mediated cleavage of fibrinogen to fibrin monomers, and activation of factors V, VIII, and XIII. Shows linear dose- and concentration-dependent prolongation of ACT, aPTT, PT, and TT.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Immediate.

Duration: Coagulation times return to baseline ~1 hour following discontinuation of infusion.

Protein binding, plasma: Does not bind other than thrombin.

Metabolism: Proteolytic cleavage.

Half-life elimination:

Neonates, Infants, Children, and Adolescents: GFR ≥30 mL/minute: 15 to 18 minutes (Forbes 2011).

Adults:

Normal renal function and mild renal impairment: 25 minutes.

Moderate renal impairment: 34 minutes.

Severe renal impairment: 57 minutes.

Dialysis: 3.5 hours.

Excretion: Urine (20%), glomerular filtration, tubular secretion, and tubular reabsorption.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance is reduced by 21% in moderate and severe renal impairment and by 70% in dialysis patients.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AR) Argentina: Amuprux;
(AT) Austria: Angiox | Bivalirudin accord;
(AU) Australia: Angiomax | Apo bivalirudin;
(BE) Belgium: Bivalirudin accord;
(CN) China: Tai jia ning;
(CO) Colombia: Angiomax;
(DE) Germany: Angiox | Bivalirudin accord | Bivalirudin cipla;
(EE) Estonia: Bivacard;
(ES) Spain: Angiox | Bivalirudina accord | Bivalirudina sala;
(FI) Finland: Angiox | Bivalirudin accord | Bivalirudin Reig Jofre;
(FR) France: Angiox | Bivalirudine Accord;
(GB) United Kingdom: Angiox | Bivalirudin Reig Jofre;
(GR) Greece: Angiox;
(HU) Hungary: Angiox;
(IE) Ireland: Angiox;
(IN) India: Bivacard | Bivacs | Bivaflo | Bivamax | Bivasave | Bivastat | Flopace | Nubimax;
(IT) Italy: Bivalirudina accord;
(LT) Lithuania: Angiox;
(LV) Latvia: Angiox;
(NL) Netherlands: Angiox | Bivalirudine Accord;
(NO) Norway: Angiox;
(NZ) New Zealand: Angiomax;
(PE) Peru: Angiomax;
(PL) Poland: Biwalirudyna accord;
(PR) Puerto Rico: Angiomax;
(PT) Portugal: Angiox | Bivalirudin accord;
(QA) Qatar: Bivasave;
(RO) Romania: Angiox;
(RU) Russian Federation: Angiox | Bivalirudin j;
(SE) Sweden: Angiox | Bivalirudin accord | Bivalirudin Reig Jofre;
(SI) Slovenia: Angiox | Bivalirudin accord;
(TR) Turkey: Bivacard

Advanced Cardiac Therapies Improving Outcomes Network (ACTION). Direct thrombin inhibitor (DTI) harmonization protocol for VADs. https://myactioneducation.org/wp-content/uploads/2023/12/ACTION_HP_Guidelines_20231221_lo.pdf. Updated December 19, 2023. Accessed February 6, 2024.
Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e44S-e88S. doi:10.1378/chest.11-2292 [PubMed 22315269]
Allie DE, Lirtzman MD, Wyatt CH, et al, “Bivalirudin as a Foundation Anticoagulant in Peripheral Vascular Disease: A Safe and Feasible Alternative for Renal and Iliac Interventions," J Invasive Cardiol, 2003, 15(6):334-42. [PubMed 12777673]
Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017. [PubMed 25260718]
Angiomax (bivalirudin) [prescribing information]. Princeton, NJ: Sandoz Inc; June 2019.
Angiomax (bivalirudin) [product monograph]. Mississauga, Ontario, Canada: Sunovion Pharmaceuticals Canada Inc.; September 2016.
Angiomax RTU (bivalirudin) [prescribing information]. Princeton, NJ: Sandoz Inc; August 2019.
Antman EM, “Should Bivalirudin Replace Heparin During Percutaneous Coronary Interventions?” JAMA, 2003, 289:903-5. [PubMed 12588276]
Aggarwal A, Sobel BE, and Schneider DJ, “Decreased Platelet Reactivity in Blood Anticoagulated With Bivalirudin or Enoxaparin Compared With Unfractionated Heparin: Implications for Coronary Intervention,” J Thromb Thrombolysis, 2002, 13:161-5. [PubMed 12355033]
Bittl JA, Chaitman BR, Feit F, et al, “Bivalirudin Versus Heparin During Coronary Angioplasty for Unstable or Postinfarction Angina: Final Report Reanalysis of the Bivalirudin Angioplasty Study,” Am Heart J, 2001, 142:952-9. [PubMed 11717596]
Bittl JA, Strony J, Brinker JA, et al, “Treatment With Bivalirudin (Hirulog) as Compared With Heparin During Coronary Angioplasty for Unstable or Postinfarction Angina. Hirulog Angioplasty Study Investigators,” N Engl J Med, 1995, 333(12):764-9. [PubMed 7643883]
Bivalirudin injection [prescribing information]. Deerfield, IL: Baxter Healthcare; January 2021.
Bivalirudin injection [prescribing information]. Deerfield, IL: Baxter Healthcare; May 2018.
Bivalirudin injection [prescribing information]. Princeton, NJ: Dr. Reddy's Laboratories, Inc; July 2019.
Bivalirudin injection RTU [prescribing information]. Princeton, NJ: MAIA Pharmaceuticals Inc; May 2023.
Chanas T, Palkimas S, Maitland HS, Liszewski A. Evaluation of the use of argatroban or bivalirudin for the management of suspected heparin-induced thrombocytopenia in the setting of continuous renal replacement therapy. Clin Med Insights: Trauma Intensive Med. 2019. doi: 10.1177/1179560319846452.
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392. doi:10.1182/bloodadvances.2018024489 [PubMed 30482768]
Dager WE. Anticoagulation Therapy. 2nd ed. American Society of Health-System Pharmacists; 2018.
Dager WE, Dougherty JA, Nguyen PH, et al, “Heparin-Induced Thrombocytopenia: Treatment Options and Special Considerations,” Pharmacotherapy, 2007, 27(4):564-87. [PubMed 17381384]
Dang CH, Durkalski VL, and Nappi JM. Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia. Pharmacotherapy. 2006;26(4):461-468. [PubMed 16553503]
Dangas GD, Mehran R, Nikolsky E, et al, “Effect of Switching Antithrombin Agents for Primary Angioplasty in Acute Myocardial Infarction: The HORIZONS-SWITCH Analysis,” J Am Coll Cardiol, 2001, 57(23):2309-11. [PubMed 21636031]
Davis Z, Anderson R, Short D, et al, “Favorable Outcome With Bivalirudin Anticoagulation During Cardiopulmonary Bypass,” Ann Thorac Surg, 2003, 75(1):264-5. [PubMed 12537226]
Delhaye C, Wakabayashi K, Maluenda G, et al. Body mass index and bleeding complications after percutaneous coronary intervention: does bivalirudin make a difference? Am Heart J. 2010;159(6):1139-1146. doi:10.1016/j.ahj.2010.03.011 [PubMed 20569731]
Dyke CM, Aldea G, Koster A, et al. Off-pump coronary artery bypass with bivalirudin for patients with heparin-induced thrombocytopenia or antiplatelet factor four/heparin antibodies. Ann Thorac Surg. 2007;84(3):836-840. [PubMed 17720385]
Dyke CM, Smedira NG, Koster A, et al. A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study. J Thorac Cardiovasc Surg. 2006;131(3):533-539. doi:10.1016/j.jtcvs.2005.09.057 [PubMed 16515902]
Erlinge D, Omerovic E, Frobert O, et al. Bivalirudin versus heparin monotherapy in myocardial infarction. N Engl J Med. 2017;377:1132-1142. [PubMed 28844201]
Expert opinion. Senior Obesity Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.;
Forbes TJ, Hijazi ZM, Young G, et al. Pediatric catheterization laboratory anticoagulation with bivalirudin. Catheter Cardiovasc Interv. 2011;77(5):671-679. doi:10.1002/ccd.22817 [PubMed 21433272]
Fuchs J and Cannon CP, “Hirulog in the Treatment of Unstable Angina. Results of the Thrombin Inhibition in Myocardial Ischemia (TIMI) 7 Trial,” Circulation, 1995, 92(4):727-33. [PubMed 7641350]
Guyatt GH, Akl EA, Crowther M, et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(suppl):7-47. [PubMed 22315257]
Hamzah M, Jarden AM, Ezetendu C, Stewart R. Evaluation of bivalirudin as an alternative to heparin for systemic anticoagulation in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2020;21(9):827-834. doi:10.1097/PCC.0000000000002384 [PubMed 32404633]
Hamzah M, Seelhammer TG, Beshish AG, et al. Bivalirudin or heparin for systemic anticoagulation during pediatric extracorporeal membrane oxygenation: multicenter retrospective study. Thromb Res. 2023;229: 178-186. doi:10.1016/j.thromres.2023.07.012 [PubMed 37517208]
Han Y, Guo J, Zheng Y, et al. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: The BRIGHT randomized clinical trial. JAMA. 2015;313(13):1336-1346. [PubMed 25775052]
Hasija S, Talwar S, Makhija N, et al. Randomized controlled trial of heparin versus bivalirudin anticoagulation in acyanotic children undergoing open heart surgery. J Cardiothorac Vasc Anesth. 2018;32(6):2633-2640. doi:10.1053/j.jvca.2018.04.028 [PubMed 30482701]
Kiser TH, Fish DN. Evaluation of bivalirudin treatment for heparin-induced thrombocytopenia in critically ill patients with hepatic and/or renal dysfunction. Pharmacotherapy. 2006;26(4):452-460. doi: 10.1592/phco.26.4.452. [PubMed 16553502]
Kiser TH, Burch JC, Klem PM, Hassell KL. Safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia. Pharmacotherapy. 2008;28(9):1115-1124. doi: 10.1592/phco.28.9.1115. [PubMed 18752382]
Koster A, Chew D, Grundel M, et al. An Assessment of Different Filter Systems for Extracorporeal Elimination of Bivalirudin: An In Vitro Study. Anesth Analg. 2003;96(5):1316-1319. [PubMed 12707125]
Koster A, Chew D, Grundel M, et al. Bivalirudin Monitored With the Ecarin Clotting Time for Anticoagulation During Cardiopulmonary Bypass. Anesth Analg. 2003;96(2):383-386.
Koster A, Dyke CM, Aldea G, et al. Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: results of the CHOOSE-ON trial. Ann Thorac Surg. 2007;83(2):572-577. [PubMed 17257990]
Koster A, Spiess B, Chew DP, et al. Effectiveness of Bivalirudin as a Replacement for Heparin During Cardiopulmonary Bypass in Patients Undergoing Coronary Artery Bypass Grafting. Am J Cardiol. 2004;93(3):356-359. [PubMed 14759391]
Kuchulakanti P, Wolfram R, Torguson R, et al. Brachytherapy and bivalirudin evaluation study. Am Heart J. 2005;150(4):832-837. [PubMed 16209990]
Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006 [PubMed 34895950]
Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade Compared With Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Intervention. REPLACE-2 Randomized Trial. JAMA. 2003;289(7):853-863. [PubMed 12588269]
Lincoff AM, Kleiman NS, Kereiakes DJ, et al. Long-Term Efficacy of Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade vs Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Revascularization: REPLACE-2 Randomized Trial. JAMA. 2004;292(6):696-703. [PubMed 15304466]
Lincoff AM, Kleiman NS, Kottke-Marchant K, et al. Bivalirudin With Planned or Provisional Abciximab Versus Low-Dose Heparin and Abciximab During Percutaneous Coronary Revascularization: Results of the Comparison of Abciximab Complications With Hirulog for Ischemic Events Trial (CACHET). Am Heart J. 2002;143(5):847-853. [PubMed 12040347]
Linkins L, Dans AL, Moores LK, et al. Treatment and Prevention of Heparin-Induced Thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(suppl):e495S-e530S. [PubMed 22315270]
Merry AF, Raudkivi PJ, Middleton NG, et al. Bivalirudin Versus Heparin and Protamine in Off-Pump Coronary Artery Bypass Surgery. Ann Thorac Surg. 2004;77:925-931. [PubMed 14992900]
Nagle EL, Dager WE, Duby JJ, et al. Bivalirudin in pediatric patients maintained on extracorporeal life support. Pediatr Crit Care Med. 2013;14(4):e182-e188. doi:10.1097/PCC.0b013e31827200b6 [PubMed 23648880]
Neuhaus KL, Molhoek GP, Zeymer U, et al. Recombinant Hirudin (Lepirudin) for the Improvement of Thrombolysis With Streptokinase in Patients With Acute Myocardial Infarction: Results of the HIT-4 Trial. J Am Coll Cardiol. 1999;34(4):966-973. [PubMed 10520777]
O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. [PubMed 23247304]
Ranucci M, Ballotta A, Kandil H, et al. Bivalirudin-based versus conventional heparin anticoagulation for postcardiotomy extracorporeal membrane oxygenation. Crit Care. 2011;15(6):R275. doi:10.1186/cc10556 [PubMed 22099212]
Rayapudi S, Torres A Jr, Deshpande GG, et al. Bivalirudin for anticoagulation in children. Pediatr Blood Cancer. 2008;51(6):798-801. doi:10.1002/pbc.21731 [PubMed 18819124]
Refer to manufacturer's labeling.
Robson R. The Use of Bivalirudin in Patients With Renal Impairment. J Invasive Cardiol. 2000;12:33F-36F. [PubMed 11156732]
Rocca B, Fox KAA, Ajjan RA, et al. Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. Eur Heart J. 2018;39(19):1672-1686f. doi:10.1093/eurheartj/ehy066 [PubMed 29509886]
Runyan CL, Cabral KP, Riker RR, et al. Correlation of bivalirudin dose with creatinine clearance during treatment of heparin-induced thrombocytopenia. Pharmacotherapy. 2011;31(9):850-856. doi: 10.1592/phco.31.9.850. [PubMed 21923585]
Salter BS, Weiner MM, Trinh MA, et al. Heparin-induced thrombocytopenia: a comprehensive clinical review. J Am Coll Cardiol. 2016;67(21):2519-2532. doi:10.1016/j.jacc.2016.02.073 [PubMed 27230048]
Seelhammer TG, Bohman JK, Schulte PJ, Hanson AC, Aganga DO. Comparison of bivalirudin versus heparin for maintenance systemic anticoagulation during adult and pediatric extracorporeal membrane oxygenation. Crit Care Med. 2021;49(9):1481-1492. doi:10.1097/CCM.0000000000005033 [PubMed 33870916]
Seybert AL, Coons JC, Zerumsky K. Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin? Pharmacotherapy. 2006;26(2):229-241. [PubMed 16466327]
Shammas NW, Lemke JH, Dippel EJ, et al. Bivalirudin in Peripheral Vascular Interventions: A Single Center Experience. J Invasive Cardiol. 2003;15(7):401-404. [PubMed 12840239]
Shahzad A, Kemp I, Mars C, et al; for the HEAT-PPCI trial investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial [published online July 5, 2014]. Lancet. doi: 10.1016/S0140-6736(14)60924-7. [PubMed 25002178]
Smedira NG, Dyke CM, Koster A, et al. Anticoagulation With Bivalirudin For Off-Pump Coronary Artery Bypass Grafting: The Results Of The EVOLUTION-OFF Study. J Thorac Cardiovasc Surg. 2006;131(3):686-692. [PubMed 16515924]
Steg PG, van 't Hof A, Hamm CW, et al; EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med. 2013;369(23):2207-2217. doi: 10.1056/NEJMoa1311096. [PubMed 24171490]
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for Patients With Acute Coronary Syndromes. N Engl J Med. 2006;355(21):2203-2216. [PubMed 17124018]
Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin During Primary PCI in Acute Myocardial Infarction. N Engl J Med. 2008;358(21):2218-2230. [PubMed 18499566]
Tsu LV, Dager WE. Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia. Ann Pharmacother. 2011;45(10):1185-1192. doi: 10.1345/aph.1Q177. [PubMed 21881032]
Tsu LV, Dager WE. Comparison of bivalirudin dosing strategies using total, adjusted, and ideal body weights in obese patients with heparin-induced thrombocytopenia. Pharmacotherapy. 2012;32(1):20-26. doi:10.1002/PHAR.1016 [PubMed 22392825]
Valgimigli M, Frigoli E, Leonardi S, et al. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med. 2015;373(11):997-1009. [PubMed 26324049]
Vasquez JC, Vichiendilokkul A, Mahmood S, et al. Anticoagulation With Bivalirudin During Cardiopulmonary Bypass in Cardiac Surgery. Ann Thorac Surg. 2002;74(6):2177-2179. [PubMed 12643418]
Washam JB, Herzog CA, Beitelshees AL, et al; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, Council on Functional Genomics and Translational Biology, Council on the Kidney in Cardiovascular Disease, Council on Quality of Care and Outcomes Research. Pharmacotherapy in chronic kidney disease patients presenting with acute coronary syndrome: a scientific statement from the American Heart Association. Circulation. 2015;131(12):1123-1149. doi: 10.1161/CIR.0000000000000183. [PubMed 25712269]
Wisler JW, Washam JB, Becker RC. Evaluation of dose requirements for prolonged bivalirudin administration in patients with renal insufficiency and suspected heparin-induced thrombocytopenia. J Thromb Thrombolysis. 2012;33(3):287-295. doi: 10.1007/s11239-011-0677-3. [PubMed 22271374]
Young G, Tarantino MD, Wohrley J, Weber LC, Belvedere M, Nugent DJ. Pilot dose-finding and safety study of bivalirudin in infants <6 months of age with thrombosis. J Thromb Haemost. 2007;5(8):1654-1659. doi:10.1111/j.1538-7836.2007.02623.x [PubMed 17663736]
Zamora R. Successful anticoagulation with bivalirudin in antithrombin-deficient pediatric patient undergoing stent placement. Catheter Cardiovasc Interv. 2006;68(2):292-295. doi: 10.1002/ccd.20739 [PubMed 16819775]

Topic 144295 Version 46.0

خرید پکیج

Bivalirudin: Pediatric drug information