bivalirudin (Rx)

>10%

Back pain (42%)

General pain (15%)

Nausea (15%)

Hemorrhage, minor (13.6%)

Headache (12%)

Hypotension (12%)

1-10%

Injection site pain (8%)

Insomnia (7%)

Pelvic pain (6%)

Hypertension (6%)

Anxiety (6%)

Vomiting (6%)

Bradycardia (5%)

Dyspepsia (5%)

Abdominal pain (5%)

Fever (5%)

Nervousness (5%)

Urinary retention (4%)

Hemorrhage, major (2.3%)

≥3g/dL fall in Hgb (1.9%)

TIMI minor bleeding (1.3%)

RBC transfusions (1.3%)

Postmarketing Reports

Pulmonary hemorrhage

Cardiac tamponade

INR increased

Contraindications

Active major bleeding

Hypersensitivity

Cautions

Bleeding may occur

Use caution in renal impairment

Not for IM administration

Intended for use with aspirin

Hemorrhage may occur at any site; discontinue bivalirudin if unexplained fall in blood pressure or hematocrit occurs

Use with caution in patients with disease states associated with increased risk of bleeding; monitor patients on therapy for signs and symptoms of bleeding; monitor patients with disease states associated with an increased risk of bleeding more frequently for bleeding

An increased risk of thrombus formation, including fatal outcomes, reported with use of bivalirudin in gamma brachytherapy; if decision made to use bivalirudin during brachytherapy procedures, maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within catheter or vessels

Bivalirudin affects international normalized ratio (INR); INR measurements made in patients treated with bivalirudin may not be useful for determining appropriate dose of warfarin

Acute stent thrombosis (<4 hr) reported at a greater frequency with bivalirudin compared to heparin treated patients; patients should remain for at least 24 hr in a facility capable of managing ischemic complications and should be carefully monitored following primary PCI for signs and symptoms consistent with myocardial ischemia

Pregnancy

There are no data available in pregnant women to inform a drug-associated risk of adverse developmental outcomes

Animal data

• Reproduction studies in rats and rabbits administered subcutaneously doses up to 1.6 times and 3.2 times maximum recommended human dose (MRHD) of 15 mg/kg/day based on body surface area (BSA) during organogenesis, respectively, revealed no evidence of fetal harm

Lactation

Not known whether drug is present in human milk; no data are available on effects on breastfed child or on milk production; developmental and health benefits of breastfeeding should be considered along with clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Competitive, direct thrombin inhibitor; thrombin enables fibrinogen conversion to fibrin during the coagulation cascade; Inhibition of fibrinogen conversion to fibrin inhibits thrombus development

Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation

Synthetic analog of hirudin

Pharmacokinetics

Half-Life: 25 min (normal renal function); 57 min (severe renal impairment)

Duration: ~ 1 hr after infusion discontinued

Protein Bound: Minimal

Clearance: 60-89 mL/min; Reduced in severe renal impairment

Metabolism: Blood proteases

Excretion: renal

Dialyzable: Yes

IV Incompatibilities

No incompatibilities observed with glass bottles or polyvinyl chloride bags & administration sets

Y-site: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, dobutamine (concentrations 4mg/mL or greater), prochlorperazine, reteplase, streptokinase, vancomycin

IV Compatibilities

Solution: D5W, NS

Y-site: abciximab, alfentanil, ampicillin, ampicillin/sulbactam, azithromycin, ciprofloxacin, diphenhydramine, dobutamine (compatible at concentrations up to 4mg/mL; incompatible at 12.5mg/mL), dopamine, epinephrine, fentanyl, furosemide, heparin, lidocaine, lorazepam, MgSO4, midazolam, morphine SO4, KCl, NaHCO3, TMP-SMX, warfarin, most cephalosporins

IV Preparation

To each 250 mg vial add 5 mL SWI

Gently swirl until all material is dissolved

Dilute each vial in 50 mL of D5W or NS to yield a final concentration of 5 mg/mL

If low-rate infusion is used after initial infusion, a lower concentration bag should be prepared

Inspect for particulate matter and discoloration prior to administration

Do not use preparations containing particulate matter

Reconstituted drug will be a clear to slightly opalescent, colorless to slightly yellow solution

IV Administration

Initial bolus injection followed by continuous infusion

Storage

Store bivalirudin dosage units at 20-25°C (68-77°F); excursions of 15-30°C permitted

Do not freeze reconstituted or diluted bivalirudin

Reconstituted material may be stored at 2-8°C up to 24 hours

Diluted bivalirudin with a concentration between 0.5mg/mL and 5mg/mL is stable at room temperature for up to 24 hours

Discard any unused portion of reconstituted solution remaining in vial