Shehri Presentation Dec 2009 Abuse of State Property in Karachi
1 Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates Supervised by: Dr.Mohammad Elfaour...
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Transcript of 1 Presented by: Manar Lashkar Samah Al-shehri Pharm.D candidates Supervised by: Dr.Mohammad Elfaour...
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Presented by: Manar LashkarSamah Al-shehriPharm.D candidates
Supervised by:
Dr.Mohammad Elfaour
King Faisal Specialist Hospital and Research Center
(2007-1428)
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Introduction
The American College of Chest Physicians (ACCP) recommends treating these patients with oral warfarin to maintain an international normalized ratio (INR) of 2.0–3.0.
Oral warfarin is the standard of care for patients requiring long-term anticoagulation due to venous thromboembolic disease.
Achieving a therapeutic INR may be complicated by many factors, such as drug-drug interactions, drug-food interactions, and inadequate absorption of drugs.
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Introduction
Normally Warfarin sodium is completely absorbed after oral administration with peak concentration generally attained within the first 4 hours.
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Introduction Patients with Crohn's disease may have
reduced absorption of warfarin in the small bowel due to loss of effective surface area secondary to:
chronic inflammation ulcerative lesions resection
In such cases the oral anticoagulant
therapy is not applicable.
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Introduction So, the usual alternative
outpatient anticoagulation is achieved by subcutaneous low molecular weight heparin (LMW heparin) e.g. enoxaparin and tinzaparin.
What about if
LMW heparin is contraindicated?!
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Introduction In cases like pyoderma gangrenosum
(which is a complication of Crohn’s disease that causes tissue to become necrotic causing deep ulcers and worsened by subcutaneous injections),
oral warfarin and SC LMW heparin are not useful…
What is the alternative?!
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Intravenous Warfarin as an Alternative for
Anticoagulation
In this presentation we will discuss a case report published in Pharmacotherapy Journal in 2007 that describes the successful use of intravenous warfarin in a patient with upper extremity thrombosis who was resistant to oral warfarin and cannot tolerate the SC LMW heparin.
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Case Report Patient information: A 27-year-old, 40-kg, Caucasian woman
Complain:Malnourishment secondary to end-stage Crohn's disease.Blocked central venous catheter line that had been inserted 6 weeks earlier for administration of total parenteral nutrition (TPN).
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Case Report Medical History:• Multiple surgical procedures, including a
colectomy with a primary closure for her Crohn's disease.
• Pyoderma gangrenosumDrug administration on admission:• Hydromorphone IV• Dimenhydrinate IV• Furosemide IV• Total parenteral nutrition• Sublingual lorazepam
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Case Report Lab results: Hepatic transaminase levels and platelet
count were within normal limits and remained stable throughout her admission.
Diagnostic tools:Doppler ultrasonography confirmed that the patient had developed an upper extremity thrombosis extending from the right jugular to the subclavian vein, secondary to her central line.
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Thromboembolic Treatment
New central line was inserted, and anticoagulation with an intravenous heparin infusion along with oral warfarin was started.
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Ora
l D
aily
Warf
ari
n D
ose
s (m
g)
DayDay
INR
Vitamin K discontinued
Warfarin
INR
High doses of warfarin were potentially dangerous if sudden absorption were to occur
patient was still receiving vitamin K 10 mg/week in her TPN
Next doses failed to produce a significant increase in the patient's INRINR
remained subtherapeutic
The patient
did respond
to therapy So oral warfarin
should be discontinued
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Since
Therapy was started
An alternative anticoagulant was required
The hospital's purchasing group ordered IV warfarin on hospital day 28; it arrived the next morning
IV heparin was not an option for outpatient management of the thrombus
LMW heparin was contraindicateddue to her history of pyoderma gangrenosum
The decision was made to use IV warfarin
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WarfarinINR
Day
IV D
aily
Warf
ari
n D
ose
s (m
g)
Heparin DC
INR
IV warfarin was started at 5 mg dose.
The patient began to respond to warfarin.The patient achieved her therapeutic INR
The patient stabilized on 4mg/day IV warfarin and was discharged.
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Discussion
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Warfarin Resistance
1) Hereditary.. very rare 2) Acquired: more common
Poor compliance. Exogenous vit. K intake. Increased warfarin clearance (intrinsic or
due to enzyme inducers) Decreased warfarin absorption.
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The patient was in the inpatient setting.
Achievement therapeutic INR while receiving warfarin intravenously.
vitamin K was removed from the TPN.
Patient drugs were reviewed.
Hereditary
Poor Compliance
Vitamin K intake
Drug-drug Interactions
Determining Warfarin Resistance Cause
in our Case
Increased clearance
xxxxx
Decreased absorption
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Pharmacological Facts Warfarin is an anticoagulant that inhibits
activation of vitamin K–dependent clotting factors II, VII, IX, and X and proteins C and S.
So, it works on the extrinsic clotting system which is measured by the INR.
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It is completely absorbed from the GIT and its effect is produced within 36–72 hours and lasts from 4–6 days.
Intravenous warfarin, approved for use the FDA, provides an alternative administration route for patients who cannot receive the oral formulation and cannot use subcutaneous low-molecular-weight heparins due to adverse effects
Pharmacological Facts
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But is there any differences between IV and oral warfarin??
vs
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Pharmacologically:
The efficacy and toxicity of IV warfarin is similar to that of the oral form and it is monitored by INR, prothrombin time and hemoglobin levels
Pharmacokinetically:
It should provide the patient with the same concentration of an equal oral dose.
But maximum plasma concentration will be reached earlier.
Coumadin® for Injection
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However, the full anticoagulant effect of a dose of warfarin may not be achieved until 72-96 hours after dosing.
So, IV warfarin should not provide any increased biological effect or earlier onset of action.
Warfarin for injection should be administered as a slow bolus over 1–2 minutes into a peripheral vein.
It is not to be given intramuscularly and is not approved for direct intravenous push.
Coumadin® for Injection
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However, clinical experience, including the experience with our patient, suggests that it can be administered as a direct intravenous push injection without complications.
The vial must be reconstituted with 2.7 mL of sterile water for Injection to yield 2mg/mL. So, net contents 5.4 mg of warfarin lyophilized powder.
It must be protected from light.
Coumadin® for Injection
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Coumadin® for Injection
After reconstitution, COUMADIN® for Injection is chemically and physically stable for 4 hours at room temperature.
It does not contain any antimicrobial preservative.
The vial is not recommended for multiple use and unused solution should be discarded.
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ConclusionIn this complicated patient who was resistant to oral warfarin and unable to receive subcutaneous low-molecular-weight heparin, therapeutic anticoagulation was achieved with intravenous warfarin.
Further clinical experience and reports are needed to better understand the role of intravenous warfarin in anticoagulation management.
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Criticism The title was interesting and useful in our clinical
practice. (Intravenous Warfarin as an Alternative for Anticoagulation)
The case follows a standard format (Introduction, description of the case, discussion and references).
The case described clearly and it stated the clinical importance for reporting this case.
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Criticism The patient data were reported adequately.
The treatment plan was appropriate for the problem and other options were discussed .
The author indicates direction for future management of similar cases.
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However, the article doesn’t state the exact date of patient admission and the hospital name and place.
Criticism
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References Gellatly R. Intravenous Warfarin as an Alternative for Anticoagulation.
Pharmacotherapy. 2007;27(6):933-935
Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. The
seventh ACCP conference on antithrombotic and thrombolytic therapy: antithrombotic therapy for venous thromboembolic disease. Chest 2004;126(3):401S–28.
DiDomenico RJ. Coagulants and anticoagulants. In: Anderson PO, Knoben JE, Troutman WG, eds. Handbook of clinical drug data, 10th ed. New York: McGraw-Hill Companies, Inc., 2002:615–17.
Porter RS, Sawyer WT. Warfarin. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetics: principles of therapeutic drug monitoring, 3rd ed. Vancouver, WA: Applied Therapeutics, Inc., 1992:31-1–31-46.
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References
Hulse ML. Warfarin resistance: diagnosis and therapeutic alternatives. Pharmacotherapy 1996;16(6):1009–17.
Brophy DF, Ford SL, Crouch MA. Warfarin resistance in a patient with short bowel syndrome. Pharmacotherapy 1998;18(3):646–9.
Brystol-Myers Squibb Canada, Inc. Coumadin (warfarin sodium) product monograph. Montreal, Quebec, Canada; 2005.
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Manar Lashkar Samah Al-shehri