Limitations of warfarin
Warfarin is very useful to prevent stroke in patients with atrial fibrillation and maintenance of function of a mechanical prosthetic valve. At the same time it has several limitations:
- Unpredictable response: Same dose produces different responses in terms of elevation of prothrombin time international normalized ratio (PT-INR) in different persons and in same person at different times.
- Narrow therapeutic window: Difference between toxic dose and ineffective dose is narrow. A mild increase in dose can produce a disproportionate rise in INR.
- Slow onset and offset of action: On the average it takes about 4 days for a steady INR to be obtained. Similarly waning of action also takes 4 days and these figures are quite variable.
- Food drug interactions are numerous: As an example, green leafy vegetables with high vitamin K content lowers the effectiveness of warfarin.
- Several drug-drug interactions: Drugs which are protein bound can displace warfarin and increase the INR resulting in bleeding. Drugs which enhance the metabolism can reduce the INR. Drugs like antibiotics which wipe off the intestinal bacterial flora producing vitamin K can increase the INR. It is always good practice to re-check PT-INR when any new drug has been initiated.
- Warfarin resistance: Some persons may need exceedingly high doses of warfarin, typically over 20 mg to get a therapeutic INR. This may be genetically determined, but the tests are not widely available.