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Presented by : LEE KIAN CHOY

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Introductio
n:
• 1921: Dr. Frank
Schofield discovered that
cattle died of internal
bleeding after ingesting
mouldy sweet clover
(anticoagulant).

• 1940:The potent
anticoagulant was later
identified as warfarin by
Karl Paul Link

•1954: Approved to be
used in human.

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 Prophylaxis and treatment of venous thrombosis

 Pulmonary embolism

 Thromboembolic disorder

 Artrial fibrillation with risk of embolism

 As an adjunct in the prophylaxis of systemic embolism


after myocardial infarction

 Prevention thromboembolism in pt with prosthetic heart


valve

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 Warfarin contains racemic isomer of R and S.

S isomer is 5x more potent then R.

S isomer has a rapid clearance.

In therapeutic dose, warfarin prevent vitamin-K


dependent coagulation factors by 30%-50%

It takes 2-7 days for full effect of warfarin to


appear.
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Peak plasma concentration achieved after 3-9 hours

Meals slow down but do not reduce absorption

Warfarin crosses the placenta but is not excreted in


milk

It is metabolized by the liver and excreted in the


urine.

Elimination Half life: 36-42 hours

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 Initiation treatment should be individualized (eg: hepatic function,
nutritional status, concurrent therapy & risk of bleeding)
Adult:
 Start therapy: 5-10mg daily for 2 days and monitor INR on to
determine the need for dose adjustment
 Maintenance: 2-10mg daily and continue INR monitoring on daily
basis until INR stable and monitor on weekly/monthly basis (depend
on compliance)
Infant and Children:
 Stat 0.2 mg/kg, 0.2mg/kg next day providing INR <1.3, then 0.05-
0.2mg/kg o.d =>Prophylaxis: INR 2-2.5 => Treatment: INR 2-3

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 Cardiovascular: Edema, hemorrhagic shock
 CNS: Fever, lethargy, malaise, headache, dizziness, stroke
 Dermatological: Rash, dermatitis, urticaria, pruritis, alopecia,
skin gangrene (occur in the first few weeks)
 GI: Anorexia, stomach cramps, abdominal pain, GI bleeding,
taste disturbance, mouth ulcer
 Haematological: Haemorrhage, leucopenia, retroperitoneal
hematoma, agranulocytosis
 Respiratory: Hemoptysis, pulmonary hemorrhage
 Limbs: Purple toe syndrome (several weeks after treatment)
 Hepatic: Jaundice, increase in transaminases
 Genitourinary: Hematuria

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 Pregnancy (Category X)
 Alcoholism, dementia, psychoses
 Bleeding tendency (eg: hemophilia/
 Undergoing a surgical procedure
 Recent intracranial haemorrhage
 Tendency to fall
 Condition predisposing to GI haemorrhage
 Severe hepatic impairment
 Uncontrolled hypertension?????

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Indication Targeted INR Targeted INR
Range
Thromboembolism in patient
with prosthetic heart valve 2.5-3.5 3.0

Other conditions (eg: MI &


venous thromboembolism) 2.0-3.0 2.5

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 Warfarin isomer S is metabolized by CYP2C9

Warfarin isomer R is metabolized by CYP1A2 &


CYP3A4

 Warfarin can interact with approximately 250


kinds of drug

 Note: Refer to the list given

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 Decrease coagulation: Coenzyme Q10 & St
John’s Wort

Increase coagulation: Dong Quai, evening


primrose, red clover, garlic, green tea, ginseng
& gingko biloba

Food high in Vit-K allows the formation of


prothrombin to occur

Note: Avoid alcohol intake as it can affect INR


Refer to the list of food given

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Warfarin is used as it is the only anti-
coagulant form that can be administered in
tablet form (others are admininstered via
IV/SC)

It was shown that warfarin can reduce risk of


stroke by 60% as compared to aspirin 20%.

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 Diet: Maintain normal diet after initiation of
warfarin therapy

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Check INR 3 days after taking oral antibiotics

Remember to provide patient with warfarin card and


advice them to show it to the pharmacist everytime
they purchase any OTC or medication fill-ups.

Patient should be educated in modifiable risk factor


for stroke and MI (eg: HPT & dyslipideamia, smoking &
DM)

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 Take at the same time every day to avoid INR fluctuation
Note: Provide “anticoagulant book “ to allow patient to keep track with their dose.

 Avoid brand switching as different brands are not


bioequivalence

 Inform your Dr before undergoing any surgical procedure

 Educate patient to spot signs of bleeding (eg: unexplained


bruising, red urine, red/dark faeces, gum bleeding)

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Warfarin available in Miri hospital
1mg (pink), 2mg(lavender), 5mg(peach)

List B drug

INR = (PT patient / PT normal )


Note: Normal PT = ???????

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 Streif, W et al. 1999, ‘Analysis of Warfarin Therapy in Pediatric Patients: A
Prospective Cohort Study of 319 Patients ‘, blood, Vol. 94 No. 9 , pp.3007-
3014

 Charles, F.L et al. 2005, Drug Information Handbook, Lexi-Comp

 Bluebook 2009

 Hua, H.S, Lee, G.L, Peng, H.C 2005, Sarawak handbook of medical
emergencies, C.E publishing, Kuching

 Product information leaflet

 MIMs online, viewed 23/05/09


<http://mims.hcn.net.au.ezlibproxy.unisa.edu.au/ifmx-nsapi/mims-data/?
MIval=2MIMS_abbr_pi&product_code=305&product_name=Coumadin>

 Australian Medicine Handbook (2007)

 Shann, F 2001, Drug Doses, Royal Children’s Hospital, Victoria

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