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Bivalirudine Drug Presentation From Nicvd Dhaka
Bivalirudine Drug Presentation From Nicvd Dhaka
DRUG PRESENTATION
Co ordinator- Dr Rampada Sarker Asst Prof of Cardiac Surgery, NICVD. Presented By- Dr. Manoz Kr. Sarker MS (Thesis Part), NICVD.
Introduction
1. Anticoagulant is a drug which inhibits the action clotting factors. 2. Commonly used anticoagulants warfarin , given by mouth, and heparin, given by injection. 3. Close medical supervision and dose adjusted on the basis of test results is required. 4. Doses if too low may not prevent clots, too high may cause severe bleeding.
History
Anticoagulants in use for more than 70 years to prevent and treat potentially deadly blood clots 1930s: The advent of heparin 1950s: The first oral anticoagulants 1980s: Overcoming the drawbacks of Unfractionated heparin 2000s: Direct Thrombin Inhibitor DTIs and indirect Factor Xa inhibitors developed 2008: Development of the first oral direct Factor Xa inhibitor
Bivalirudin
CHEMISTRY
Bivalirudin
CHEMICAL STRUCTURE
Mechanism of Action
Bivalirudin
Bivalirudin is an analogue of the peptide hirudin. It is a specific and reversible direct thrombin inhibitor that works by binding to the catalytic and anionic exosite of circulating and clot-bound thrombin.
Pharmacokinetics
Generic Name: Bivalirudin Drug Category: Anti Coagulant ( Direct Acting AntiThrombin) Biotransformation : Mostly In Liver and other sites by means of Proteolysis Elimination: Rapid plasma clearance by both a renal mechanism and proteolytic cleavage
Half Life:
Pharmacodynamics
I/V Bivalirudin
immediate anticoagulant effect. Bivalirudin has a linear dose-dependent pharmacologic effect,. ACT, aPTT, thrombin time, and prothrombin time as the Bivalirudin dose is increased Coagulation parameters return to baseline values approximately 1 hour after cessation of the infusion. The effect on aPTT profiles is similar in patients with normal, mild, or moderately reduced renal function.
DRUG DESCRIPTION
White lyophilized cake, Marketed as 250 mg bivalirudin in 125 mg mannitol, and sodium hydroxide to adjust the pH to 5-6 When reconstituted with Sterile Water clear to opalescent, colorless to slightly yellow solution, pH 5-6.
Indication
Deep venous thrombosis,
Pulmonary embolism, Acute arterial occlusion. After an acute myocardial infarction Unstable angina pectoris Prevention of thromboses in surgery with extracorporeal circulation In Patients With Potential Heparin-Induced Thrombocytopenia/ protamine sensitivity Hemodialysis, Maintenance of open venous catheters
Contradication
Patients with: Active major bleeding; Hypersensitivity to Bivalirudin or its components. Patient with severe renal disease/failure Patient with severe Hepatic disease/failure.
Side Effects
Common :Anxiety; nervousness headache;
nausea;vomiting.; pain at the injection site Allergic reactions : (Mild-Moderate-Severe) Less Common : back, stomach, or pelvic pain; trouble sleeping; upset stomach; Rarely : Arrhythmias ,altered level of alertness , confusion; difficulty urinating; dizziness; easy bruising , fainting; shortness of breath; vision or speech changes.
Heparine Vs Bivaluridine
Facts
Binding with Thrombin Inactivation Plasma Protine Binding Thrombine Inhibition Ab. formation
Heparine
Inability to inactivate fibrin-bound thrombin, neutralized by platelet factor 4
Bivaluridine
Inhibit both fluid phase & fibrin bound thrombin Not so Bind sp. To Thrombin Complete inhibition Not so
Platelate activation
do platelet activation
No activation
Heparine Vs Bivaluridine
Facts
Thrombocytopenia Cost Effectiveness Availability Antidote/Revarsal Working site
Heparine
Induce Thrombocytopenia Cheaper Easily Available Protamine In vivo & in vitro
Bivaluridine
Not so Costly Avaiable at western world. * No such Recommended for in vitro
Major bleeding
All-cause mortality Cardiac mortality Reinfarction
6.9
10.5
5.9
7.7
0.75 (0.580.97)
0.03
2.9
5.1
6.2
8.2
Drug Interactions
BIVALURIDINE
Bivalirudin REACTING DRUG Aceno coumarol RESULT bivalirudin causes additive toxicity with acenocoumarol bivalirudin causes additive toxicity with additive toxicity additive effect additive effect
Alteplase
Anistreplase
additive toxicity
Drug Interactions
BIVALURIDINE
Bivalirudin Bivalirudin Bivalirudin REACTING DRUG Clopidogrel Enoxaparin Heparin Heparins, low-molecularweight Phenindione Prasugrel RESULT additive effect additive effect additive effect
Bivalirudin
additive effect
Bivalirudin Bivalirudin
Dosing
FDA-approved dosage of bivalirudin for patients undergoing PTCA :---------
I/V bolus dose of 1.0 mg/kg 4-hour infusion of 2.5 mg/kg/hour. an additional intravenous infusion (0.2 mg/kg/hr) may be given for up to 18 hours ( if indicated ) Patients undergoing stent placement, (lower dosages) 0.75 mg/kg 1.75 mg/kg/hr through the end of the procedure were administered without any apparent reduction in efficacy.***yet to approved by FDA
Dosing
Pt with Heparin induced Thrombocytopenia undergoing Cardiac
Surgery.
Pt with hypersensitivity to Heparin undergoing Cardiac Surgery. Pt with Protamine hypersensitivity undergoing Cardiac Surgery. Starting with :
I/V bolus dose of 1.0 mg/kg hourly infusion of 2.5 mg/kg/hour(for 2-3 hours)
Conversion
to Warfarin
days
Time to peak antithrombotic effect of Bivalirudin is
INR reaches desired therapeutic range, discontinue Bivalirudin (after a minimum of four days)
Monitoring
PRIOR TO ADMINISTRATION
a. Baseline aPTT/PT b. Baseline serum creatinine c. calculated creatinine clearance MONITORING PTT/DTI 4 hourly . 2 hours after initiation of therapy . subsequent checks 2 hrs after any change in dose .Immediately prior to resuming therapy if infusion has been held .Any time if thromboembolism or hemorrhage are suspected.
Recent studies
Current Clinical Applications of Bivalirudin: An Overview Author(s): Nicolas W. Shammas, MS, MD (n = 2151) (6.2% versus 7.9%, p = 0.0386). Conclution: The Food and Drug Administration (FDA) approved the use of bivalirudin in patients undergoing percutaneous coronary angioplasty
Recent studies
Bivalirudin was associated with lower bleeding complications than low-dose unfractionated heparin in PCI patients at high bleeding risk in the ARMYDABIVALVE study. Author Dr Giuseppe Patti Conclution : - Bivalirudin was associated with lower bleeding complications .
A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass:
Conclusion
Limitations of heparin include incomplete anticoagulation, heparin resistance, and the increasingly relevant development of heparin antibodies. Bivalirudin, a reversible direct thrombin inhibitor with a short half-life, is an intriguing alternative to heparin and has properties that may improve outcomes.