Bivalirudin

Bivalirudin is an anticoagulant agent belonging to Direct thrombin Inhibitor.

Bivalirudin is a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia and to prevent thrombosis during percutaneous coronary intervention.

The mean steady state bivalirudin concentration of 12.3 ± 1.7 mcg/mL is achieved following an IV bolus of 1 mg/kg and a 4hour 2.5 mg/kg/h IV infusion. Bivalirudin does not bind to plasma proteins (other than thrombin) or to red blood cells. Bivalirudin is metabolized by proteolytic cleavage. Bivalirudin has a half-life of 25 minutes in PTCA patients with normal renal function. The total body clearance of bivalirudin in PTCA patients with normal renal function is 3.4 mL/min/kg. Bivalirudin undergoes glomerular filtration. Tubular secretion and tubular reabsorption are also implicated in the excretion of bivalirudin, although the extent is unknown.

Bivalirudin shows common side effects like Abdominal pain or swelling, arm, back, or jaw pain, black, tarry stools, blood in the eyes, blood in the urine, blurred vision, bruising or purple areas on the skin, chest pain or discomfort, chest tightness or heaviness, confusion, coughing up blood, decreased alertness, dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly, headache, joint pain or swelling, nausea, nervousness, nosebleeds, pounding in the ears, shortness of breath, slow, fast, or irregular heartbeat, sweating, unusual tiredness or weakness.

Bivalirudin is available in the form of Intravenous powder for Injection and Intravenous ready-to-use solution.

Bivalirudin is available in India, US, UK, New Zealand, Canada, China, Russia and Australia.

Bivalirudin belonging to the Direct thrombin Inhibitor, acts as an anticoagulant agent.

Bivalirudin 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.

The immediate onset of action is achieved while taking Bivalirudin.

The Data of Tmax and duration of Action of Bivalirudin is not available.

Bivalirudin is available in the form of Intravenous powder for Injection and Intravenous ready-to-use solution.

Bivalirudin is given intravenously After initial bolus dose (when recommended), administer as a continuous infusion.

Bivalirudin is indicated for use as an anticoagulant for use in patients undergoing percutaneous coronary intervention (PCI) including patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.

Bivalirudin is an anticoagulant agent belonging to Direct thrombin inhibitor.

Bivalirudin is a specific and reversible direct thrombin inhibitor that works by binding to the catalytic and anionic exosite of circulating and clot-bound thrombin. It is used as an anticoagulant in percutaneous coronary intervention.

Bivalirudin is approved for use in the following clinical indications

Bivalirudin is indicated for use as an anticoagulant in patients with heparin-induced thrombocytopenia.

Bivalirudin with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) as listed in the REPLACE-2 trial is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI). Bivalirudin is indicated for patients with, or at risk of, heparin induced thrombocytopenia (HIT), or heparin induced thrombocytopenia and thrombosis syndrome (HITTS) undergoing PCI.

Although not approved, there have been certain off-label indications. These include

Initial dose: 0.15 to 0.2 mg/kg/hour; adjust to aPTT 1.5 to 2.5 times baseline value.

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.

Start direct-acting oral anticoagulant when bivalirudin infusion is stopped (consult local protocol if the aPTT is above the target range).

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.

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.

Initial bolus: 0.75 mg/kg followed by continuous infusion.

Maintenance continuous infusion: 1.75 mg/kg/hour to maintain ACT >300 seconds.

Initial bolus: 1 to 1.25 mg/kg followed by continuous infusion; add 50 mg bolus to priming solution of cardiopulmonary bypass (CPB) circuit.

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.

Bivalirudin is available in various strengths as 250 mg and 250 mg/50 mL.

Bivalirudin is available in the form of Intravenous powder for Injection and Intravenous ready-to-use solution.

Bolus: No dosage adjustment necessary.

CrCl ≥30 mL/minute: 1.75 mg/kg/hour.

CrCl <30 mL/minute: 1 mg/kg/hour.

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.

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.

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.

Avoid echinacea, herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Bivalirudin is contraindicated in patients with

Active major bleeding

Hypersensitivity (e.g., anaphylaxis) to Bivalirudin or its components

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.

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.

Increased risk of intracoronary thrombus formation has been reported with the use of gamma brachytherapy even with the use of higher doses as compared to doses used for beta radiation. If used during brachytherapy, maintain a meticulous catheter technique with frequent aspiration and flushing while minimizing conditions of stasis within the catheter or vessels.

It is not known whether bivalirudin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Bivalirudin is administered to a nursing woman.

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.

Avoid echinacea, herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Thrombosis, hemorrhage (including intracranial hemorrhage, major hemorrhage, and retroperitoneal hemorrhage), antibody development.

Cardiac tamponade, coronary thrombosis (during PCI, including intracoronary brachytherapy), increased INR, pulmonary hemorrhage, anaphylaxis, hypersensitivity reaction.

The common side effects of Bivalirudin include the following

Abdominal pain or swelling, arm, back, or jaw pain, black, tarry stools, blood in the eyes, blood in the urine, blurred vision, bruising or purple areas on the skin, chest pain or discomfort, chest tightness or heaviness, confusion, coughing up blood, decreased alertness, dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly, headache, joint pain or swelling, nausea, nervousness, nosebleeds, pounding in the ears, shortness of breath, slow, fast, or irregular heartbeat, sweating, unusual tiredness or weakness.

Decrease in frequency of urination, decrease in urine volume, difficulty in passing urine (dribbling), lightheadedness or fainting, painful urination.

Blue lips and fingernails, changes in skin color, cold hands and feet, cough or hoarseness, coughing that sometimes produces a pink frothy sputum, difficult, fast, noisy breathing, sometimes with wheezing, fever or chills, increased blood pressure, increased thirst, loss of appetite, lower back or side pain, pain, redness, or swelling in the arm or leg, pale skin, paralysis of the face, rapid, shallow breathing, severe numbness, especially on one side of the face or body, swelling in the legs and ankles, swelling of the face, fingers, or lower legs, troubled breathing, vomiting, weight gain.

Reproductive studies have been performed in rats at subcutaneous doses up to 150 mg/kg/day, (1.6 times the maximum recommended human dose based on body surface area) and rabbits at subcutaneous doses up to 150 mg/kg/day (3.2 times the maximum recommended human dose based on body surface area). These studies revealed no evidence of impaired fertility or harm to the fetus attributable to bivalirudin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Bivalirudin 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, Bivalirudin and aspirin should be used together during pregnancy only if clearly needed.

It is not known whether bivalirudin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Bivalirudin is administered to a nursing woman.

As per FDA, safety and effectiveness of Bivalirudin in pediatric patients have not been established.

In studies of patients undergoing PCI, 44% were ≥65 years of age and 12% of patients were ≥75 years old. Elderly patients experienced more bleeding events than younger patients. Patients treated with Bivalirudin experienced fewer bleeding events in each age stratum, compared to heparin.

Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of Bivalirudin have been reported in clinical trials and in post marketing 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 Bivalirudin immediately and monitor the patient closely for signs of bleeding. There is no known antidote to Bivalirudin. Bivalirudin is hemodialyzable.

Bivalirudin 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.

The mean steady state bivalirudin concentration of 12.3 ± 1.7 mcg/mL is achieved following an IV bolus of 1 mg/kg and a 4hour 2.5 mg/kg/h IV infusion.

Bivalirudin does not bind to plasma proteins (other than thrombin) or to red blood cells.

Bivalirudin is metabolized by proteolytic cleavage. Bivalirudin has a half-life of 25 minutes in PTCA patients with normal renal function. The total body clearance of bivalirudin in PTCA patients with normal renal function is 3.4 mL/min/kg. Bivalirudin undergoes glomerular filtration. Tubular secretion and tubular reabsorption are also implicated in the excretion of bivalirudin, although the extent is unknown.

There are some clinical studies of the drug Bivalirudin mentioned below: