Warfarin Dosing Guide2

WARFARIN DOSING GUIDE
A. Warfarin Initiation
1.0 Dosing Initiation
1.1 Initiation dose may start with doses between 5 and 10 mg for the first 1 or 2
days for most individuals and subsequent dosing based in the INR response
1.2 In elderly patients or in patients who are debilitated, malnourished, have CHF,
have liver disease, have had recent major surgery, or are taking medications
known to increase the sensitivity to warfarin (eg, amiodarone), the starting dose
should be of < 5mg with subsequent dosing based on the INR response.
2.0 Monitoring
2.1 Baseline PT/INR/PTTT, full blood count (FBC) with platelets and liver function
test (LFT) should be obtained prior to warfarin initiation. If baseline level not
available, it should be obtained within 24 hours.
2.2 In hospitalized patients, PT monitoring is usually performed daily, starting after
the second or third dose until the target therapeutic range has been achieved
and maintained for at least 2 consecutive days; then two or three times weekly
for 1 to 2 weeks; then less often, depending on the stability of INR results.
2.3 In outpatients, initial monitoring may be reduced to every few days until a stable
dose response has been achieved. When the INR response is stable, the
frequency of testing can be reduced to intervals as long as every 4-8 weeks.
3.0 Suggested Algorithm For Initiating Warfarin (Goal INR 2-3*)
or

B. Potential factors that cause fluctuations of INR
a. Patient adherence:
i. Dosing error (tablet change?) or extra dose
b. Infection and/or antibiotic use
i. Antibiotics may alter patient response to warfarin
c. Drug-drug interaction
i. Start with any prescription drugs, over-the-counter drugs, or herbal or
natural remedies since last visit?
ii. Stop any of these?
iii. Did the dosage of these drug change?
d. Alcohol consumption
e. Co-morbid condition (heart failure, thyroid disorder)
f. Significant dietary change
Exclusion of factors affecting INR must be done prior to dosage adjustment.
Always search for the cause of out-of range values and address them before adjusting the
dose.
C. Warfarin Dose Adjustment Guideline
1.0 Estimation of INR response
Expect a 15% dose adjustment to result in an approximately 1.0 INR change.
Locally, for simplicity, we use 1% increase in warfarin dose correspond to increase in INR
of 0.1
2.0 Stopping 1 day of warfarin, INR could reduce in average of 0.26 (range from 0.2 - 0.5).

TARGET INR 2.5 (Range 2.0 – 3.0)
TARGET INR 3.0 ( Range 2.5 – 3.5)
Notes:
1. Always consider trend in INRs when making warfarin management decisions.
Exclusion of factors affecting INR must be done prior to dosage adjustment.
2. Consider repeating the INR same day or next day if observed value markedly different than
expected value. (Potential lab error exist).

3. Dose should be rounded up to the nearest 0.5mg.
4. Maximum changes of daily dose is + 1.0mg.
Example 1 : Subtherapeutic INR
Example 3: Supratherapeutic
Refer attachment
D. Managing Elevated INR
1. Relation between the INR and the risk of bleeding.
a. The risk of bleeding increases when the INR exceeds 4, and the risk rises sharply with
values > 5.
b. An INR above 5 requires close monitoring.
c. Intervention is required based on the INR reading, the presence of bleeding and the
patient’s underlying condition.
2. Three approaches can be taken to lower an elevated INR:
a. Temporary withdrawal of warfarin.
i. (Discontinuation of warfarin results in very slow reversal of anticoagulations.
- the INR falls over several days.)

. Administration of vitamin K.
(INR declines substantially within 24 hours after treatment with oral Vitamin K)
c. Transfusion of coagulation factors.
- To infuse fresh plasma (FFP) or prothrombin concentrate (PCC).
(Most rapidly effective measure).
The choice of approach is based largely on the potential risk of bleeding, the
presence of active bleeding, and the level of INR.
3. Most important question to answer:
a. If yes, then reversal and referral may be necessary
b. If no, then less aggressive actions can be taken
c. If low risk for bleeding, holding doses is sufficient
d. If very high risk for bleeding, oral vitamin K may be appropriate
4. If the patient has no bleeding, management strategy should be informed by the future risk
of bleeding
a. Low to moderate bleed risk, hold warfarin doses
b. If very high bleed risk, to give oral vitamin K dose
I. INR > 10
II. Very advanced age (> 80 years) or frailty
III. History of falls or high risk for falls
IV. History of bleeding
V. Recent surgery

E. Recommendations for Managing Elevated INRs or Bleeding in Patients Receiving Warfarin
INR Clinical Setting Therapeutic Options
More than
therapeutic
range but <
5.0
> 5.0, but
< 9.0
No significant
bleeding.
Rapid reversal
required.
E.g.: Patient requires
urgent surgery.
No significant
bleeding
Rapid reversal
required.
> 9.0 No significant
bleeding
At any
elevation of
INR
At any
elevation of
INR
Rapid reversal
required.
Lower dose or omit dose;
Monitor more frequently and
Resume at lower dose when INR therapeutic;
If only minimally above therapeutic range,
no dose reduction may be required.
Hold warfarin and give Vitamin K 1mg IV infusion or
2mg po.
Omit next one or two doses,
Monitor more frequently and
Resume at an appropriately adjusted dose when INR
in therapeutic range.
Alternatively, omit dose and give Vitamin K (1-2.5mg
PO) particularly if at increased risk of bleeding.
Hold warfarin and give vitamin K 1-2mg IV infusion
or 2-5mg po with the expectation that the reduction
of INR will occur in 24 hour.
Hold warfarin therapy and give higher dose of
vitamin K (2.5–5 mg po) with the expectation that
the INR will be reduced substantially in 24–48 h
Monitor more frequently and use additional
vitamin K if necessary.
Resume therapy at an appropriately adjusted
dose when INR is therapeutic.
Hold warfarin and give vitamin K 1 – 10mg IV
and may repeat 6 – 24hour as necessary.
Serious bleeding Hold warfarin therapy and
Give vitamin K (10 mg by slow IV infusion) and
supplemented with FFP (Fresh Frozen Plasma), PCC
(Prothrombin Complex Concentrate), or
recombinant factor VIIa, depending on the urgency
of the situation;
Vitamin K can be repeated q12h for persistent INR
elevation.
Life threatening
bleeding
E.g. intracranial
hemorrhage.
Hold warfarin therapy and
Give PCC (Prothrombin Complex Concentrate)
supplemented with vitamin K (10 mg by slow IV
infusion).
Recombinant factor VIIa may be considered as
alternative to PCC.
Repeat, if necessary, depending on INR.

Considerations for Vitamin K
1. Comparison of route of administration for Vitamin K
Route Advantages Disadvantages
IV
Subcutaneous
Oral
Fastest Onset of Action
Lower risk of anaphylaxis
Safer route.
Low risk of anaphylaxis
No IV site needed.
Must be given by slow IV infusion.
Warfarin resistance.
Delayed onset
Unpredictable response.
Least desired route.
Slower onset of action
Warfarin resistance.
2. Vitamin K Dosing
• HIGH dose of vitamin K, though effective, may lower the INR more than is necessary and
may lead to warfarin resistance for a week or more, resulting in an increased risk of
thromboembolism.
• LOW doses of vitamin K are recommended.
INR
Effective dose range
(oral)
Anticipating reduction of INR
5.0 – 9.0 1.0 – 2.5 mg Within 24 hours.
> 9.0 2.5 – 5.0mg Within 24 – 48 hours
• Vitamin K can also be given as slow Vitamin K infusion when there is a greater urgency to
reverse anticoagulation. (lower INR within 12- 14 hours)
Rapid Reversal of anticoagulation:
• Administration of coagulation factors provides only a temporary solution due to the short
half-life of the provided clotting factors (3-4 hours for Factor VII), compared with a duration
of action of 2 to 5 days for warfarin, as well as relative instability of clotting factors upon
administration.
• Administration of either fresh frozen plasma or factor concentrates will decrease the PT/INR
for 4 to 6 hours.
• Complete return to a therapeutic INR will require supplementation with vitamin K.

Supratherapeutic Dosing Adjustment
Attachment
1 2
3
4
5 6
7
8
9
D. Reference:
1. Ministry of Health Malaysia,
Pharmaceutical Services Division.
Medication Therapy Adherence
Clinic: Warfarin Protocol, 2010.