Warfarin dosing

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.

6. 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.

7. 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

8. 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

9. 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

10. 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

11. 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/

12. 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.

13. 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

14. 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

15. References Amir Jaffer , Lee B ragg , practical tips for warfarin dosing and monitoring , Cleveland clinic journal of medicine , 2003, O xford 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