Bivalirudina Uses, Dosage, Side Effects and more
Bivalirudina directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions.In in vitro studies, bivalirudin inhibited both soluble (free) and clot-bound thrombin, was not neutralized by products of the platelet release reaction, and prolonged the activated partialthromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) of normal human plasma in a concentration-dependent manner. The clinical relevance of these findings is unknown.
Bivalirudina mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.
| Trade Name | Bivalirudina |
| Availability | Prescription only |
| Generic | Bivalirudin |
| Bivalirudin Other Names | Bivalirudin, Bivalirudina, Bivalirudinum |
| Related Drugs | amlodipine, aspirin, metoprolol, carvedilol, propranolol, clopidogrel, atenolol, Plavix, Integrilin, Angiomax |
| Type | |
| Formula | C98H138N24O33 |
| Weight | Average: 2180.2853 Monoisotopic: 2178.985813062 |
| Protein binding | Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | Anti-platelet drugs |
| Manufacturer | |
| Available Country | |
| Last Updated: | January 7, 2025 at 1:49 am |
Uses
Bivalirudina is used for:
- Anticoagulant in Patients Undergoing PTCA/PCI or PCI with HITS/HITTS
- Unstable Angina/Non-ST-Elevation MI (Off-label)
- STEMI Undergoing Primary PCI (Off-label)
- Heparin-induced Thrombocytopenia
Renal Impairment: The clearance of Bivalirudina was reduced approximately 20% in patients with moderate and severe renal impairment and was reduced approximately 80% in dialysis-dependent patients.The infusion dose of Bivalirudina may need to be reduced, and anticoagulant status monitored in patients with renal impairment
- ClCr 30 to 50 mL/min: Administer infusion at rate of 1.75 mg/kg/h.
- ClCr less than 30 mL/min: Reduce infusion rate to 1 mg/kg/h.
Pediatric Use: The safety and effectiveness of Bivalirudina in pediatric patients have not been established.
Geriatric Use: Elderly patients experienced more bleeding events than younger patients. Patients treated with Bivalirudina experienced fewer bleeding events in each age stratum, compared to heparin.
Bivalirudina is also used to associated treatment for these conditions: Acute Coronary Syndrome (ACS), Thrombotic events
How Bivalirudina works
Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.
Dosage
PCI/PTCA: IV Bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for duration of PCI procedure. Five minutes after bolus dose, obtain ACT and administer additional bolus of 0.3 mg/kg if indicated.
HIT/HITTS: IV Bolus dose of 0.75 mg/kg, followed by a continuous infusion at a rate of 1.75 mg/kg/h for the duration of the procedure.
Continuation of Therapy: IV Infusion may be continued for up to 4 h post-procedure as indicated. After 4 h, an additional IV infusion of 0.2 mg/kg/h for up to 20 h may be given if needed.
Concomitant Therapy: Bivalirudina is intended for concurrent use with aspirin (300 to 325 mg/day).
- For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
- Reconstitute powder for injection with 5 mL sterile water for injection. Gently swirl until powder is dissolved.
- For initial bolus infusion, further dilute each reconstituted via in 50 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 5 mg/mL.
- For low rate infusion, further dilute each reconstituted vial in 500 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 0.5 mg/mL.
- Do not mix with the following drugs in the same IV line: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, dobutamine, prochlorperazine, reteplase, streptokinase, vancomycin.
- Reconstituted bivalirudin should be a clear to slightly opalescent, colorless to slightly yellow solution. Do not administer if reconstituted or diluted solution is discolored, cloudy, or contains particulate matter.
- Maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.
- Discard any unused reconstituted or diluted solution.
Side Effects
- Bleeding, Body as a Whole: fever,infection, sepsis;
- Cardiovascular: hypotension, syncope, vascular anomaly,ventricular fibrillation;
- Nervous: cerebral ischemia, confusion, facialparalysis;
- Respiratory: lung edema;
- Urogenital: kidney failure, oliguria.
Toxicity
Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.
Precaution
Bleeding Events: Although most bleeding associated with the use of Bivalirudina in PCI/PTCA occurs at the site of arterial puncture, hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of Bivalirudina administration. Bivalirudina should be used with caution in patients with disease states associated with an increased risk of bleeding.
Coronary Artery Brachy therapy: An increased risk of thrombus formation, including fatal outcomes, has been associated with the use of Bivalirudina in gamma brachytherapy. If a decision is made to use Bivalirudina during brachytherapy procedures, maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.
Interaction
Co-administration of Bivalirudina with heparin, warfarin, thrombolytics, or GPIs was associated with increased risks of major bleeding events.
Food Interaction
- Avoid echinacea.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Drug Interaction
Unknown: arginine, arginine, levocarnitine, levocarnitine, cysteine, cysteine, lithium, lithium, valproic acid, valproic acid, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, cholecalciferol, cholecalciferol, phytonadione, phytonadione, menaquinone, menaquinone
Disease Interaction
Major: active bleedingModerate: renal impairment
Volume of Distribution
0.2L/kg
Elimination Route
Following intravenous administration, bivalirudin exhibits linear pharmacokinetics. The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.
Half Life
- Normal renal function: 25 min (in normal conditions)
- Creatinine clearance 10-29mL/min: 57min
- Dialysis-dependant patients: 3.5h
Clearance
- 3.4 mL/min/kg [Normal renal function]
- 3.4 mL/min/kg [mild renal function]
- 2.7 mL/min/kg [moderate renal function]
- 2.8 mL/min/kg [severe renal function]
- 1 mL/min/kg [Dialysis-dependent patients]
Elimination Route
Bivalirudina is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.
Pregnancy & Breastfeeding use
Pregnancy Category B. No adequate and well-controlled studies in pregnant women. As animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Bivalirudina is intended for use with aspirin . Because of possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Bivalirudina and aspirin should be used together during pregnancy only if clearly needed.
Nursing Mothers: It is not known whether bivalirudin is excreted in human milk. As many drugs are excreted in human milk, caution should be exercised when Bivalirudina is administered to a nursing woman.
Contraindication
Bivalirudina is contraindicated in patients with: Active major
bleeding & Hypersensitivity (e.g., anaphylaxis) to Bivalirudina or its components
Acute Overdose
Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of Bivalirudina have been reported in clinical trials and in postmarketing reports. A number of the reported overdoses were due to failure to adjust the infusion dose of bivalirudin in persons with renal dysfunction including persons on hemodialysis . Bleeding, as well as deaths due to hemorrhage, have been observed in some reports of overdose. In cases of suspected overdosage, discontinue Bivalirudina immediately and monitor the patient closely for signs of bleeding. There is no known antidote to Bivalirudina. Bivalirudina is hemodialyzable
Storage Condition
Store at temperature not exceeding 30º C in a dry place. Do not freeze. Keep out of reach of children
Innovators Monograph
Bivalirudina contains Bivalirudin see full prescribing information from innovator Monograph, MSDS, FDA label
