initiation of warfarin and dose adjustment. how to increase and decrease the doses. INR monitoring for bleeding. food and drug interactions.

1. Warfarin Dosing
Ahmad Al-Jalehawi
MSc Clinical pharmacy
Al-Kafeel university

2. Depend on the device used
Low m medium and high thrombogenicity
Usual target INR 2-3

3. https://bpac.org.nz/BT/2010/November/inr.aspx

4. • For most patients, vitamin K antagonists should be initiated at a
maintenance dosage of 5 mg per day.
• Older patients and persons with liver disease, poor nutritional status, or
heart failure may require lower initiation dosages.
• Diarrhea, fever, and hyperthyroidism can also potentiate the effect of
vitamin K antagonists
• An advantage to evening administration is the ability to adjust or hold the
dose the same day that the INR result becomes available.
• In general, a missed dose of warfarin is reflected in the INR within about
2 to 5 days after the dose is missed.
• There are several regimen to start warfarin

5. Heparin should be continued until the INR has been ≥ 2 for at least two consecutive days
or for five days
Standard induction regimen commenced with heparin cover
• We prefer starting with 5 mg rather than 10 mg as over-anticoagulation
is less likely, particularly in the elderly and those with liver disease or
cardiac failure.
• If the baseline INR≤1.3 the patient will receive 5mg of warfarin once daily
on days 1 and 2.
• The INR is checked on day 3 and 4 and the warfarin dose is adjusted
according to the schedule.

7. This relates to patients with intracranial or rapid-onset neurological signs, intra-ocular (not
conjunctival) bleeds, compartment syndrome, pericardial bleeds or those with active
bleeding and shock, or any bleeding that requires complete reversal of anticoagulation
within 6-8 hours.
These patients need urgent clinical assessment of clotting.
Anticoagulation due to warfarin can be effectively reversed with PCC and phytomenadione
5mg by slow intravenous injection.
Major / life threatening bleeding requiring immediate complete reversal
PCC (prothrombin complex concentrate ) contains significantly higher amounts of the clotting factors
compared to FFP ( fresh frozen plasma) ; one dose of PCC equals 8 to 16 units of FFP.

8. INR 5.0 or greater
• Omit warfarin
• Give IV phytomenadione 1-3mg (or 5-10mg if anticoagulation is to be stopped)
INR less than 5
• A clinical decision needs to be made as to whether lowering the INR is required. If this
is the case, consider giving IV phytomenadione 1-3 mg and modifying warfarin dose
High INRs in non-bleeding patients
The cause of the elevated INR should be investigated
INR ≥ 5.0 and < 8.0
• stop warfarin for 1-2 days and reduce maintenance dose
INR ≥ 8.0
• stop warfarin until INR< 5.0
• give oral phytomenadione 5 mg
Oral vitamin K will have an effect within 16-24 hours
Unexpected bleeding at therapeutic levels—always investigate possibility of underlying cause
e.g. unsuspected renal or gastro-intestinal tract pathology
Non-major bleeding

10. If the INR falls to < 1.7 in the first 4 weeks after starting treatment for
acute VTE we recommend re-starting LMWH until the INR is back to ≥2.0
Management of subtherapeutic anticoagulation

11. After a baseline INR is determined, the next INR should be obtained after the
patient has received two or three doses of the vitamin K antagonist.
Monitoring should then be decreased to twice weekly until the INR is within the
therapeutic range, then decreased to weekly, every other week, and finally
monthly.
The ACCP guidelines recommend INR monitoring once every 12 weeks for patients
who are stable (defined as at least three months of consistent results with no
required adjustment of vitamin K antagonist dosing)
Monitoring

12. Check for interactions
• Foods with high vitamin K
concentrations, such as
leafy green vegetables,
have the potential to
partially reverse
anticoagulation effects of
the vitamin K antagonist. A
consistent diet is more
important than limiting
dietary vitamin K

13. Compared with vitamin K antagonists, direct oral anticoagulants have the advantage of not
requiring direct monitoring, having minimal drug-food interactions, and having a quicker
onset of action to therapeutic effect.
Direct oral anticoagulants have fewer overall drug-drug interactions ; a comparable (if not
lower) bleeding rate; a shorter half-life; and fixed dosing based on indication, drug
interactions, and renal or hepatic function.
https://natfonline.org/anticoagulant-comparison-chart/

14. In most cases, if the dosage needs to be adjusted, then it should be
adjusted by 5% to 20% of the total weekly dose, depending on
the current INR, the previous dose, and any changes identified that may
have been the cause for the INR to be too high or too low.

15. Some situation one needs to give different doses on different days of the week.
It is better if the doses are similar rather than greatly different.
For example, if a patient were taking warfarin 2 mg daily except 4 mg on Monday and
Friday using 2-mg tablets (18 mg/week) , it would be reasonable to change the dosage
to 3 mg daily except 2 mg on Monday, Wednesday, and Friday ( 18 mg/ week )if the INR
tended to fluctuate regularly.
The patient would still receive 18 mg/week, but with less variability in the day to-day
dose. Obviously, this type of regimen may not work for every patient, as it could be
confusing or the patient may have difficulty splitting tablets. Nevertheless, the point is
that the warfarin dosage needs to be individualized

16. • In our practice, if a patient starts on Coumadin, we continue to
prescribe it.
• However, if a patient wants generic warfarin because it is cheaper,
we make this change but monitor the INR more frequently in the
first few weeks of the transition
Change to Generic

17. References
• Amir Jaffer , Lee Bragg ,practical tips for warfarin dosing and monitoring , Cleveland clinic journal of
medicine , 2003,
• Oxford hemophilia and thrombosis center protocols for outpatient oral anticoagulation with vitamin k
antagonists , ac protocols version 4.1 may 2017
• Patricia wigle ,et al .anticoagulation: updated guidelines for outpatient management , 2019 American academy
of family physicians