Q: Some of my patients on warfarin (Coumadin) have widely fluctuating international normalized ratios (INRs). Why is this?

Knowing reasons why INRs fluctuate will assist in making warfarin dose changes. Even patients who have been stabilized on warfarin for some time may experience unexpected volatility. Both pharmacokinetic and pharmacodynamic factors may drive these fluctuations. Here are some factors to consider: Does the patient sometimes forget a dose? If the patient forgets a dose, do they "double up" the dose to offset the missed dose? If the INR is unexpectedly low, inquire about medication compliance. It is important to emphasize that patients must call the healthcare provider for advice if they miss a dose (Hull et al., 2018).

Has there been a recent warfarin brand change? Because warfarin is absorbed quickly, there have been rare instances when substituting brands could alter the INR (Enwere et al., 2015). Patients should be advised to remain consistent with one brand. Has the patient recently initiated or stopped any prescriptions? INRs can increase if a patient has been prescribed antibiotics (Enwere et al.). This usually happens within 1 week of therapy initiation and the interaction magnitude is unpredictable. To be cautious, the INR should be monitored more frequently for a few weeks when discontinuing or initiating a new prescription (Hull et al., 2018). Also, inquire about vitamins, herbals, or nonprescriptions medication. Many patients do not recognize these as medications. For instance, a multivitamin, with additional vitamin K could decrease INR levels due to warfarin resistance. Likewise, question if patients are taking nonsteroidal anti-inflammatory drugs. Such medications have been correlated with increased INR (Hull et al.).

Have the patient's eating habits changed recently? If patients consume a high or low intake of vitamin K fortified foods, they may respectively exhibit warfarin sensitivity or resistance (Moss & Cifu, 2015). Consuming small amounts of vitamin K foods should not be problematic, but instruct patients to avoid eating an overabundance of particular foods including brussel sprouts, mustard greens, kale, chard, spinach, collard, asparagus, and broccoli (Moss & Cifu). Patients must be urged to be consistent with their dietary intake. Likewise, alcoholic drinks can increase warfarin metabolism and amplify anticoagulation by reducing the breakdown of warfarin (Moss & Cifu).

Has the patient experienced a new illness? When patients experience an acute airway illness, they can encounter an INR increase, which may be directly related to a decline in hepatic oxygenation causing a decrease in elimination (Kovacs et al., 2015). Also, patients can encounter a decline in appetite throughout the acute illness. Similarly, if patients experienced diarrheal illnesses, of any sorts, they will likely experience decreased vitamin K absorption, increasing the sensitivity to warfarin (Moss & Cifu, 2015). This upsets the vitamin K and warfarin stasis, causing an increase in INR.

Unfortunately, warfarin can be affected by a multitude of influences, both pharmacokinetic and pharmacodynamic. As a result, patient's individualized warfarin therapy, and their INRs must be monitored carefully. Patients are unique human beings and, therefore, each patient's response to anticoagulation is highly personalized.

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