Bivalirudin

Last updated on RxList: 2/23/2017
Bivalirudin Side Effects Center

Last reviewed on RxList 02/24/2017

Bivalirudin (bivalirudin injection, powder, lyophilized, for solution) is a direct thrombin inhibitor indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA); undergoing percutaneous coronary intervention (PCI) with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) as in the REPLACE-2 study; and with, or at risk of, heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS), undergoing PCI. Bivalirudin for injection is intended for use with aspirin. Bivalirudin is available in generic form. Common side effects of bivalirudin include:

The dosage of bivalirudin for patients who do not have HIT/HITTS, undergoing PCI/PTCA is 0.75 mg/kg intravenous (IV) bolus dose followed immediately by a 1.75 mg/kg/h IV infusion for the duration of the procedure. The dosage of bivalirudin for patients who have HIT/HITTS, undergoing PCI is 0.75 mg/kg IV bolus dose followed immediately by a 1.75 mg/kg/h IV infusion for the duration of the procedure. Bivalirudin may interact with heparin, warfarin, thrombolytics, or GPIs. Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant or plan to become pregnant before using bivalirudin; it is not expected to harm a fetus. Bivalirudin is intended for use with aspirin. Because of possible adverse effects on the newborn and the potential for increased maternal bleeding, particularly during the third trimester, bivalirudin and aspirin should be used together during pregnancy only if clearly needed. It is unknown if bivalirudin passes into breast milk. Consult your doctor before breastfeeding.

Our Bivalirudin (bivalirudin injection, powder, lyophilized, for solution) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Bivalirudin Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

  • a light-headed feeling, like you might pass out;
  • easy bruising or bleeding (nosebleeds, bleeding gums, heavy menstrual bleeding);
  • bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • sudden numbness or weakness, problems with vision or speech;
  • urine that looks red, pink, or brown;
  • swelling or redness in an arm or leg; or
  • bleeding from wounds or needle injections, any bleeding that will not stop.

Bleeding is the most common side effect of bivalirudin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Bivalirudin (Bivalirudin Injection)

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Bivalirudin Professional Information

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Bleeding

In 6,010 patients undergoing PCI treated in the REPLACE-2 trial, bivalirudin patients exhibited statistically significantly lower rates of bleeding, transfusions, and thrombocytopenia as noted in Table 2.

Table 2: Major Hematologic Outcomes REPLACE-2 (Safety Population)

  Bivalirudin with “provisional” GPI1
(n=2,914)
Heparin + GPI
(n=2,987)
Protocol defined major hemorrhage2 (%) 2.3% 4.0%
Protocol defined minor hemorrhage3 (%) 13.6% 25.8%
TIMI defined bleeding4    
- Major 0.6% 0.9%
- Minor 1.3% 2.9%
Non-access site bleeding    
- Retroperitoneal bleeding 0.2% 0.5%
- Intracranial bleeding <0.1% 0.1%
Access site bleeding    
- Sheath site bleeding 0.9% 2.4%
Thrombocytopenia5    
<100,000 0.7% 1.7%
<50,000 0.3% 0.6%
Transfusions    
- RBC 1.3% 1.9%
- Platelets 0.3% 0.6%
1GPIs were administered to 7.2% of patients in the bivalirudin with provisional GPI group.
2Defined as the occurrence of any of the following: intracranial bleeding, retroperitoneal bleeding, a transfusion of ≥ 2 units of blood/blood products, a fall in hemoglobin > 4g/dL, whether or not bleeding site is identified, spontaneous or non-spontaneous blood loss with a decrease in hemoglobin >3g/dL.
3Defined as observed bleeding that does not meet the criteria for major hemorrhage.
4TIMI major bleeding is defined as intracranial, or a fall in adjusted Hgb >5g/dL or Hct of >15%: TIMI minor bleeding is defined as a fall in adjusted Hgb of 3 to <5 g/dL or a fall in adjusted Hct of 9 to <15%, with a bleeding site such as hematuria, hematemesis, hematomas, retroperitoneal bleeding or a decrease in Hgb of >4 g/dL with no bleeding site.
5If <100,000 and >25% reduction from baseline, or <50,000.

In 4,312 patients undergoing PTCA for treatment of unstable angina in 2 randomized, double-blind studies comparing bivalirudin to heparin, bivalirudin patients exhibited lower rates of major bleeding and lower requirements for blood transfusions. The incidence of major bleeding is presented in Table 3. The incidence of major bleeding was lower in the bivalirudin group than in the heparin group.

Table 3: Major Bleeding and Transfusions in BAT Trial (all patients )*

  Bivalirudin
(n=2,161)
Heparin
(n=2,151)
No. (%) Patients with Major hemorrhage1 79 (3.7) 199 (9.3)
- with >3 g/dL fall in Hgb 41 (1.9) 124 (5.8)
- with >5 g/dL fall in Hgb 14 (0.6) 47 (2.2)
- retroperitoneal bleeding 5 (0.2) 15 (0.7)
- intracranial bleeding 1 (<0.1) 2 (0.1)
- required transfusions 43 (2.0) 123 (5.7)
*No monitoring of ACT (or PTT) was done after a target ACT was achieved.
1Major hemorrhage was defined as the occurrence of any of the following, intracranial bleeding, retroperitoneal bleeding, clinically overt bleeding with a decrease in hemoglobin ≥ 3 g/dL or leading to a transfusion of > 2 units of blood. This table includes data from the entire hospitalization period.

In the AT-BAT study, of the 51 patients with HIT/HITTS, 1 patient who did not undergo PCI had major bleeding during CABG on the day following angiography. Nine patients had minor bleeding (mostly due to access site bleeding), and 2 patients developed thrombocytopenia.

Other Adverse Reactions

Adverse reactions, other than bleeding, observed in clinical trials were similar between the bivalirudin treated patients and the control groups.

Adverse reactions (related adverse events) seen in clinical studies in patients undergoing PCI and PTCA are shown in Tables 4 and 5.

Table 4: Most Frequent (>0.2%) Treatment-related Adverse Events (reactions )(through 30 days ) in the REPLACE-2 Safety Population

  Bivalirudin with
“provisional” GPI1
(n = 2,914)
n (%)
Heparin + GPI
(n = 2,987)
n (%)
Patients with at least one treatment-related AE 78 (2.7) 115 (3.9)
Thrombocytopenia 9 (0.3) 30 (1.0)
Nausea 15 (0.5) 7 (0.2)
Hypotension 7 (0.2) 11 (0.4)
Angina pectoris 5 (0.2) 12 (0.4)
Headache 6 (0.2) 5 (0.2)
Injection site pain 3 (0.1) 8 (0.3)
Nausea and vomiting 2 (0.1) 6 (0.2)
Vomiting 3 (0.1) 5 (0.2)
1Note: A patient could have been more than one event in any category.
Abbreviation: AE = Adverse Event.

Table 5: Adverse Reactions Other Than Bleeding Occurring In ≥ 5% of Patients in Either Treatment Group in BAT Trial

Event Treatment Groups  
Bivalirudin
(n=2,161)
Heparin
(n=2,151)
Number of Patients (%)
Cardiovascular    
  Hypotension 262 (12) 371 (17)
  Hypertension 135 (6) 115 (5)
  Bradycardia 118 (5) 164 (8)
Gastrointestinal    
  Nausea 318 (15) 347 (16)
  Vomiting 138 (6) 169 (8)
  Dyspepsia 100 (5) 111 (5)
Genitourinary    
  Urinary retention 89 (4) 98 (5)
Miscellaneous    
  Back pain 916 (42) 944 (44)
  Pain 330 (15) 358 (17)
  Headache 264 (12) 225 (10)
  Injection site pain 174 (8) 274 (13)
  Insomnia 142 (7) 139 (6)
  Pelvic pain 130 (6) 169 (8)
  Anxiety 127 (6) 140 (7)
  Abdominal pain 103 (5) 104 (5)
  Fever 103 (5) 108 (5)
  Nervousness 102 (5) 87 (4)

Serious, non-bleeding adverse events were experienced in 2% of 2,161 bivalirudin-treated patients and 2% of 2,151 heparin-treated patients. The following individual serious non-bleeding adverse events were rare (>0.1% to <1%) and similar in incidence between bivalirudin- and heparin-treated patients. These events are listed by body system: Body as a Whole: fever, infection, sepsis; Cardiovascular: hypotension, syncope, vascular anomaly, ventricular fibrillation; Nervous: cerebral ischemia, confusion, facial paralysis; Respiratory: lung edema; Urogenital: kidney failure, oliguria. In the BAT trial, there was no causality assessment for adverse events.

Immunogenicity/Re-Exposure

In in vitro studies, bivalirudin exhibited no platelet aggregation response against sera from patients with a history of HIT/HITTS.

Among 494 subjects who received bivalirudin in clinical trials and were tested for antibodies, 2 subjects had treatment-emergent positive bivalirudin antibody tests. Neither subject demonstrated clinical evidence of allergic or anaphylactic reactions and repeat testing was not performed. Nine additional patients who had initial positive tests were negative on repeat testing.

Postmarketing Experience

Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during postapproval use of bivalirudin: fatal bleeding; hypersensitivity and allergic reactions including reports of anaphylaxis; lack of anticoagulant effect; thrombus formation during PCI with and without intracoronary brachytherapy, including reports of fatal outcomes; pulmonary hemorrhage; cardiac tamponade; and INR increased.

Read the entire FDA prescribing information for Bivalirudin (Bivalirudin Injection)

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© Bivalirudin Patient Information is supplied by Cerner Multum, Inc. and Bivalirudin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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