Warfarin

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 6

 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 0.050.2mg/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 Range

Targeted INR

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 13

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.30073014

 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



 Australian Medicine Handbook (2007)  Shann, F 2001, Drug Doses, Royal Children’s Hospital, Victoria

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