Probable warfarin interaction with menthol cough drops

Warfarin is a widely used and effective oral anticoagulant; however, the agent has an extensive drug and food interaction profile. We describe a 46-year-old African-American man who was receiving warfarin for a venous thromboembolism and experienced a decrease in his international normalized ratio (INR). No corresponding reduction had been made in his warfarin dosage, and no changes had been made in his concomitant drug therapy or diet. The patient's INR fell from a therapeutic value of 2.6 (target range 2-3) to 1.6 while receiving a weekly warfarin dose of 50 mg. His INR remained stable at 1.6 for 3 weeks despite incremental increases in his warfarin dose. The patient reported that he had been taking 8-10 menthol cough drops/day due to dry conditions at his workplace during the time period that the INR decreased. Five days after discontinuing the cough drops, his INR increased from 1.6 to 2.9. Over the subsequent 5 weeks, his INR was stabilized at a much lower weekly warfarin dose of 40 mg. Use of the Naranjo adverse drug reaction probability scale indicated that the decreased INR was probably related to the concomitant use of menthol cough drops during warfarin therapy. The mechanism for this interaction may be related to the potential for menthol to affect the cytochrome P450 system as an inducer and inhibitor of certain isoenzymes that would potentially interfere with the metabolism of warfarin. To our knowledge, this is the second case report of an interaction between warfarin and menthol. Patients receiving warfarin should be closely monitored, as they may choose to take over-the-counter products without considering the potential implications, and counseled about a possible interaction with menthol cough drops.