Critically Elevated INR in a Patient on Warfarin After Increase in Extended-Release Niacin Dose

OBJECTIVE: To report a case of a probable interaction between warfarin and extended-release niacin that may have led to synergistic coagulopathy and to inform health care providers of a need for more frequent monitoring of international normalized ratio (INR) in patients taking these drugs concomitantly. CASE SUMMARY: A 69-year-old white female whose anticoagulation treatment had been stable for 18 months with warfarin 2.5 mg daily (17.5 mg/wk) presented to an anticoagulation clinic with a critically elevated INR of greater than 12.3 after a dose increase in extended-release niacin (Niaspan) from 500 mg to 1000 mg daily the previous week. Extended-release niacin 500 mg daily had not affected the patient's INR for the previous 3 months; the most recent INR before this episode was 2.4. Warfarin was withheld and extended-release niacin was discontinued. The INR 2 days later was 4.8 and, with titration of warfarin to the previous maintenance dose of 2.5 mg daily, the INR was 2.3. DISCUSSION: Common drug interaction resources do not consistently list an interaction between warfarin and extended-release niacin. The mechanism of niacin-induced coagulopathy is theorized to be related to diminished coagulation factors, and limited data suggest that this may be more pronounced with extended-release niacin. Because of the described effects of niacin on the coagulation cascade and the possibility for pharmacokinetic interactions, there is a potential for synergistic coagulopathy when combined with warfarin therapy. For patients taking both medications, more frequent INR monitoring than that which drug interaction references suggest may be advised. An objective causality assessment (Horn Drug Interaction Probability Scale) revealed that the interaction was probable. CONCLUSIONS: An interaction between niacin and warfarin likely elevated the INR in this patient because of synergistic coagulopathy and pharmacokinetic effects of niacin. Increased frequency of INR monitoring may be advised for patients taking these drugs concomitantly.