Managing Anticoagulation Therapy

An Advanced Workshop for Hospital Pharmacy Practitioners Managing Warfarin Therapy Concepts to Consider
WA V| WA cA ]tzzt Zxwx V{|wx: [|t

Objectives
To correctly select an appropriate
initiation dose and titrate warfarin dosing To identify the correct INR range to target and optimal length of warfarin therapy To manage drug-drug and drug-disease interactions to avoid patient harm
4/11/2010 2

Session contents
Introduction INR Factors affecting warfarin dosing Dosing Therapeutic range Duration of therapy Reversal of anticoagulation Case study
3

4/11/2010

Warfarin pharmacokinetics
Lipid soluble; 100% bioavailability on oral administration Extremely highly plasma protein bound [99%] Small volume of distribution [7-14L] Long plasma half life [36 hours] Racemic mixture of two enantiomers, (R)- and (S)-warfarin
4/11/2010 4

Mechanism of action
Warfarin is a vitamin K antagonist that reduces the hepatic production of vitamin K dependant active coagulation factors II, VII, IX and X in a dose related way This results in the prolongation of prothrombin time [bleeding time]and a decreased tendency to form blood clots
4/11/2010 5

International Normalised Ratio [INR]

Expression - intensity of anticoagulation The prothrombin time expressed as a ratio [clotting time for patient plasma divided by the clotting time for control plasma]corrected by a standardising factor The higher the value of the INR, the greater the risk of bleeding
4/11/2010 6

Therapeutic range for warfarin

2-3 [target 2.5]for the vast majority of indications Lower target of 2-2.5 is recommended for patients on ASA and clopidogrel and low dose ASA 2.5-3.5 for some mechanical heart valves
NB. You must always know what type of valve it is and the position
4/11/2010 7

Factors affecting warfarin dosing

Drug interactions Alcohol Herbs Disease states Hepatic dysfunction Tobacco use Malnutrition
8

4/11/2010

Initiation of therapy [induction of anticoagulation]

Loading with warfarin may be undertaken rapidly depending on urgency of the indication Indications requiring rapid dosing are: DVT, PE & placement of prosthetic valve Treatment with heparin is indicated for at least 4-5 days until target INR is reached
4/11/2010 9

Induction of anticoagulation
Anticoagulation with warfarin takes 48-72 hours to develop fully Patients commencing warfarin due to atrial fibrillation do not need rapid anticoagulation or heparin anticoagulation

4/11/2010

10

Induction of anticoagulation
A range of loading-dose regimens recommended for use in the UK: Rapid loading: day 1: 10mg day 2: 10mg day 3: 5mg day 4: check INR then dose accordingly
4/11/2010 11

Induction of anticoagulation
Patients > 60 years; liver disease; cardiac failure; at high risk of bleeding day 1: 5mg or 10mg day 2: 5mg day 3: 5mg day 4: check INR then dose accordingly
4/11/2010 12

Slow-loading regimen
An example of a slow induction regimen: Men: 5mg daily and check INR on day 3 or 4 Women: 3mg daily and check INR on day 3 or 4
4/11/2010 13

Maintenance doses
Daily warfarin dose required to achieve an INR within usual ranges can be from 1mg to 15mg Warfarin sensitivity varies widely between individuals and within the same person due to variables e.g. age, diet, intercurrent illness and drugs
4/11/2010 14

Duration of warfarin therapy

Recommended treatment duration after first episode of thromboembolism is at least 3 months and may extend to 6 months depending on local policy and clinical factors

4/11/2010

15

Duration of therapy
Treatment for prophylaxis of thrombosis in patients with mechanical heart valves and patients with recurrent thromboembolism (i.e. repeated DVT or PE will be life long)

4/11/2010

16

Reversal of anticoagulation
Over-anticoagulation (INR > 4) without bleeding
Omitting one or several doses may be adequate Small dose Vitamin K1 1mg will reverse anticoagulation faster and reduce incidence of haemorrhages

4/11/2010

17

Reversal of anticoagulation
Very high INR (> 8.0) or other risk factors for bleeding (e.g. history of peptic ulcer)
Larger dose of vitamin K1 (0.5mg I.V or 5mg orally) Extreme caution with high doses of vitamin K1 as it may take a longer time to achieve anticoagulation when recommenced
4/11/2010 18

The End!
4/11/2010 19