Usage
-
Bivalirudin is prescribed as an anticoagulant (antithrombotic) in patients undergoing percutaneous coronary intervention (PCI), including those with heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). It is also used in patients with unstable angina undergoing PTCA (percutaneous transluminal coronary angioplasty) and in the treatment of patients with moderate to high risk acute coronary syndromes (ACS) due to unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) in whom early PCI is planned. It is also indicated for the treatment of patients with ACS due to ST-segment elevation myocardial infarction (STEMI) undergoing PCI.
-
Pharmacological Classification: Direct thrombin inhibitor, Anticoagulant.
-
Mechanism of Action: Bivalirudin directly inhibits thrombin, a key enzyme in the coagulation cascade, by binding to both the catalytic site and the anion-binding exosite of circulating and clot-bound thrombin. This inhibition prevents the conversion of fibrinogen to fibrin, thereby disrupting clot formation.
Alternate Names
- International Nonproprietary Name (INN): Bivalirudin
- Brand Names: Angiomax, Angiomax RTU, Bivalirudin RTU, Bivalirudin ARX, BIVACARD
How It Works
- Pharmacodynamics: Bivalirudin’s primary pharmacodynamic effect is anticoagulation via direct thrombin inhibition. This leads to a prolongation of clotting times, such as activated clotting time (ACT) and activated partial thromboplastin time (aPTT).
- Pharmacokinetics:
- Absorption: Administered intravenously, therefore 100% bioavailability.
- Metabolism: Bivalirudin is primarily metabolized by proteolysis, a process of protein breakdown, both in the blood and extravascularly. This produces inactive fragments that are then excreted. It does not undergo significant metabolism by CYP enzymes, unlike many other drugs.
- Elimination: Primarily eliminated by renal excretion (approximately 20% as unchanged drug) with a half-life of approximately 25 minutes in patients with normal renal function. Renal clearance is around 3.4 mL/min/kg in PTCA patients with normal renal function. It involves both glomerular filtration and tubular secretion and reabsorption processes.
- Mode of Action: Bivalirudin is a specific and reversible direct thrombin inhibitor. It binds to both the active catalytic site and the anion-binding exosite of thrombin, preventing thrombin-mediated fibrin formation. This binding is reversible; therefore, the duration of action is largely dependent on plasma concentration and half-life.
- Receptor Binding/Enzyme Inhibition: Bivalirudin directly inhibits thrombin, a serine protease central to the coagulation cascade. It does not interact with other receptors or enzymes significantly.
Dosage
Standard Dosage
Adults:
- PCI (without HIT/HITTS): 0.75 mg/kg IV bolus followed by 1.75 mg/kg/h IV infusion for the duration of the procedure. An ACT should be checked 5 minutes after the bolus, and an additional 0.3 mg/kg bolus administered if needed. The infusion can be extended for up to 4 hours post-PCI. In patients with STEMI the infusion should be continued for up to 4 hours post-procedure.
- PCI (with HIT/HITTS): Same as above (0.75 mg/kg IV bolus followed by a 1.75 mg/kg/h continuous infusion). The infusion can be extended for up to 4 hours post-PCI.
- ACS (initial treatment): 0.1 mg/kg IV bolus followed by a 0.25 mg/kg/h infusion.
Children:
- Bivalirudin is not FDA-approved for pediatric use. Off-label use has been reported with varying dosing regimens based on weight, age, and clinical condition. Consult specialized literature and guidelines for detailed pediatric dosing recommendations. Consider a starting dose of 0.3 mg/kg/h for those with normal creatinine clearance and 0.15 mg/kg/h for those with renal dysfunction.
Special Cases:
- Elderly Patients: Increased risk of bleeding. Close monitoring recommended. Consider dose adjustment based on renal function (GFR).
- Patients with Renal Impairment: Dose reduction is necessary. For creatinine clearance (CrCl) 30-59 mL/min, consider reducing the infusion rate, potentially to 1 mg/kg/h. For CrCl <30 mL/min or patients on dialysis, further dose reduction is advised, possibly to 0.25 mg/kg/h.
- Patients with Hepatic Dysfunction: No specific dose adjustment is typically required.
- Patients with Comorbid Conditions: Exercise caution in patients with conditions that increase bleeding risk.
Clinical Use Cases
- PCI (Percutaneous Coronary Intervention): Standard dosage as described above.
- PTCA (Percutaneous Transluminal Coronary Angioplasty): Standard PCI dosage.
- Cardiac Surgery (On-pump CABG): Continue bivalirudin infusion until 1 hour prior to surgery. Switch to unfractionated heparin (UFH).
- Cardiac Surgery (Off-pump CABG): Continue bivalirudin infusion until surgery. Just prior to surgery, administer a 0.5 mg/kg bolus followed by a 1.75 mg/kg/h infusion for the duration of the surgery.
- ACS (Acute Coronary Syndromes): See standard adult dosage.
Dosage Adjustments
- Dose adjustments are primarily based on renal function (creatinine clearance). See recommendations for renal impairment above.
Side Effects
Common Side Effects:
- Bleeding (minor or major)
- Back pain
- Nausea
- Headache
- Vomiting
- Hypotension
- Fever
- Thrombocytopenia
- Injection site pain
Rare but Serious Side Effects:
- Allergic reactions (anaphylaxis, angioedema)
- Cardiogenic shock
- Cardiac tamponade
- Stroke
- Diffuse alveolar hemorrhage
- Thrombosis (especially in the context of gamma brachytherapy)
Long-Term Effects:
- No specific long-term effects have been consistently reported.
Adverse Drug Reactions (ADR):
- Major bleeding requiring transfusion or surgical intervention.
- Allergic reactions (anaphylaxis, angioedema)
Contraindications
- Active major bleeding
- Hypersensitivity to bivalirudin or any of its components
Drug Interactions
- Increased Bleeding Risk: Other anticoagulants (heparin, warfarin, dabigatran, apixaban, rivaroxaban), thrombolytics (alteplase, reteplase, streptokinase), glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine), mifepristone, defibrotide, prothrombin complex concentrate.
- Decreased Bivalirudin Effect: Drugs that increase bivalirudin metabolism (e.g., barbiturates like butabarbital and butalbital). Drugs with pharmacodynamic antagonism (e.g., bazedoxifene/conjugated estrogens).
- CYP450 Interactions: Bivalirudin does not undergo significant CYP450 metabolism; therefore, interactions with CYP inducers or inhibitors are not clinically relevant.
- Other: Various IV incompatibilities exist (alteplase, amiodarone, amphotericin B, chlorpromazine, dobutamine, prochlorperazine, reteplase, streptokinase, vancomycin).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Formerly Category C, now classified under the revised FDA pregnancy labeling system. No adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown some adverse effects at high doses. Risk of bleeding, particularly in the third trimester. Use aspirin with caution during pregnancy.
- Breastfeeding: No data available on bivalirudin presence in human milk or its effects on breastfed infants. Exercise caution. Consider alternate anticoagulants.
Drug Profile Summary
- Mechanism of Action: Direct thrombin inhibitor, binding to both catalytic site and anion-binding exosite.
- Side Effects: Bleeding, back pain, nausea, headache, hypotension. Rarely, serious bleeding, allergic reactions.
- Contraindications: Active major bleeding, hypersensitivity.
- Drug Interactions: Other anticoagulants, thrombolytics, GPIs.
- Pregnancy & Breastfeeding: Use with caution in pregnancy only if clearly indicated. No data on breastfeeding; exercise caution.
- Dosage: 0.75 mg/kg bolus + 1.75 mg/kg/h infusion for PCI. Adjustments needed for renal impairment.
- Monitoring Parameters: Activated clotting time (ACT), aPTT, signs of bleeding, complete blood count (CBC), hemoglobin, hematocrit.
Popular Combinations
- Aspirin: Commonly used with bivalirudin in PCI to further reduce thrombotic risk.
- Clopidogrel (or other P2Y12 inhibitors): May be added for enhanced antiplatelet effects in specific situations.
Precautions
- General Precautions: Monitor for bleeding, assess renal function before and during treatment. Screen for hypersensitivity.
- Specific Populations: See dosage adjustments for renal impairment and elderly. Caution in pregnancy and breastfeeding. No established pediatric dosage.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bivalirudin?
A: For PCI in adults, the standard dosage is a 0.75 mg/kg IV bolus followed by a 1.75 mg/kg/h IV infusion. Dose adjustments are necessary for patients with renal impairment. Pediatric dosing is not established.
Q2: How does Bivalirudin differ from heparin?
A: Bivalirudin is a direct thrombin inhibitor, while heparin acts indirectly by enhancing antithrombin activity. Bivalirudin has a more predictable anticoagulant effect and a lower risk of HIT.
Q3: What are the major bleeding risks with Bivalirudin?
A: Major bleeding can occur at any site. Risk factors include concomitant use of other anticoagulants or antiplatelet agents, history of bleeding disorders, and renal insufficiency.
A: Bivalirudin is primarily metabolized by proteolysis, not by CYP enzymes.
Q5: What should be done in case of a suspected allergic reaction?
A: Discontinue bivalirudin immediately and provide supportive care as needed. Manage allergic reactions (e.g., anaphylaxis) according to standard protocols.
Q6: Is Bivalirudin safe to use in pregnancy?
A: Use with caution during pregnancy only if clearly indicated. Weigh the potential benefits against the risks of bleeding and potential fetal effects.
Q7: Can Bivalirudin be used in patients with liver disease?
A: Generally, no specific dosage adjustment is required for patients with hepatic dysfunction. However, carefully monitor for bleeding.
Q8: How should Bivalirudin be administered?
A: Bivalirudin is administered intravenously, as a bolus followed by a continuous infusion.
Q9: What monitoring parameters are important during Bivalirudin therapy?
A: Monitor ACT, aPTT, signs of bleeding, hemoglobin, hematocrit, and platelet counts. Closely observe patients for any signs of bleeding or allergic reactions.
Q10. Can Bivalirudin be used in STEMI Patients?
A: Yes, Bivalirudin is indicated for STEMI patients undergoing primary PCI. The infusion should be continued for up to 4 hours post-procedure.
