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Bivalirudin: Drug information

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

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Angiomax;
  • Bivalirudin RTU
Brand Names: Canada
  • Angiomax
Pharmacologic Category
  • Anticoagulant;
  • Anticoagulant, Direct Thrombin Inhibitor
Dosing: Adult
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: Hepatic 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).

Dosing: Older Adult

Refer to adult dosing. No dosage adjustment is needed in elderly patients with normal renal function. Puncture site hemorrhage and catheterization site hemorrhage were seen in more patients ≥65 years of age than in patients <65 years of age.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, and 3 obesity (BMI ≥30 kg/m2):

IV: Use actual body weight for weight-based dose calculations, then titrate to clinical effect (Ref). Careful monitoring for bleeding is warranted, especially in patients with BMI ≥50 kg/m2, severe renal impairment, or those that are dialysis dependent (Ref). Refer to adult dosing for indication-specific doses.

Rationale for recommendations: There are limited data evaluating the effect of obesity on dosing requirements for bivalirudin (Ref). Clearance of bivalirudin is strongly dependent upon renal function. The half-life of bivalirudin increases from ~25 minutes to 57 minutes in patients with severe renal impairment (eGFR <30 mL/minute), and up to 3.5 hours between dialysis sessions for patients that require renal replacement. A small retrospective study compared actual body weight, adjusted body weight, and ideal body weight in patients treated for heparin-induced thrombocytopenia, and actual body weight provided the closest correlation to rates observed at the target aPTT. Furthermore, this study did not identify a clear difference in clinical outcomes, including dose to achieve goal aPTT, between patients with obesity (BMI range: 30.1 to 56.2 kg/m2), and patients without obesity that received weight-based dosing (Ref). In a registry of 16,783 patients undergoing percutaneous coronary intervention, an increase in risk of major bleeding was not observed with increasing BMI, including class 3 obesity (Ref). Use of alternate weight descriptors, such as ideal body weight and adjusted body weight, are not recommended due to the risk for under dosing (Ref).

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) [contains polyethylene glycol (macrogol)]

Generic: 250 mg/50 mL in NaCl 0.9% (50 mL [DSC]); 500 mg/100 mL in NaCl 0.9% (100 mL [DSC])

Solution Reconstituted, Intravenous:

Angiomax: 250 mg (1 ea [DSC])

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

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: 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.

Usual Infusion Concentrations: Adult

IV infusion: 250 mg in 50 mL (concentration: 5 mg/mL) of D5W or NS

Use: Labeled Indications

Percutaneous coronary intervention: Anticoagulant for use in patients undergoing percutaneous coronary intervention (PCI) including patients with heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia/thrombosis syndrome (HIT/TS)

Use: Off-Label: Adult

Cardiac surgery (alternative to heparin); Heparin-induced thrombocytopenia, complicated by thrombosis

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

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).

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.

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anacaulase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: May enhance the anticoagulant effect 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 combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Caplacizumab: May enhance the anticoagulant effect 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

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

Dabigatran Etexilate: May enhance the anticoagulant effect 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 combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

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

Desirudin: Anticoagulants may enhance the anticoagulant effect 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

Edoxaban: May enhance the anticoagulant effect 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 combination

Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

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

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect 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 combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Oritavancin: May diminish the therapeutic effect 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 therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pirtobrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

Protein C Concentrate (Human): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect 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 combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Telavancin: May diminish the therapeutic effect 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 therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full Lexicomp or drug interaction monograph for details. Risk C: Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

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

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

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).

Breastfeeding Considerations

It is not known if bivalirudin is present in breast milk. The manufacturer recommends that caution be exercised when administering bivalirudin to breastfeeding women.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

ACT; aPTT; PT/INR; signs/symptoms of bleeding.

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:

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.

Pricing: US

Solution (reconstituted) (Angiomax Intravenous)

250 mg (per each): $1,170.00

Solution (reconstituted) (Bivalirudin Trifluoroacetate Intravenous)

250 mg (per each): $90.00 - $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.

Brand Names: International
  • Amuprux (AR);
  • Angiodin (BD);
  • Angiomax (AR, AU, CL, IL, NZ);
  • Angiox (AT, BE, BG, CH, DE, EE, ES, FI, FR, GB, GR, HN, HU, IS, IT, LT, LU, MT, PL, PT, RO, RU, SA, SE, SI, SK, TR);
  • Bivaflo (IN);
  • Tai Jia Ning (CN)


For country code abbreviations (show table)
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  2. 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]
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  7. Angiomax RTU (bivalirudin) [prescribing information]. Princeton, NJ: Sandoz Inc; August 2019.
  8. Antman EM, “Should Bivalirudin Replace Heparin During Percutaneous Coronary Interventions?” JAMA, 2003, 289:903-5. [PubMed 12588276]
  9. 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]
  10. 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]
  11. 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]
  12. Bivalirudin injection [prescribing information]. Deerfield, IL: Baxter Healthcare; January 2021.
  13. Bivalirudin injection [prescribing information]. Deerfield, IL: Baxter Healthcare; May 2018.
  14. Bivalirudin injection [prescribing information]. Princeton, NJ: Dr. Reddy's Laboratories, Inc; July 2019.
  15. 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.
  16. 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]
  17. Dager WE. Anticoagulation Therapy. 2nd ed. American Society of Health-System Pharmacists; 2018.
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  19. 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]
  20. 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]
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