Coagulation Counseling

APRIL 15, 2010
Anna D. Garrett, PharmD, BCPS, CPP

Interaction Between Menthol Cough Drops and Warfarin Reported

A probable interaction between warfarin and menthol cough drops has been reported in a recent issue of Pharmacotherapy. The authors describe the case of a 46-year-old African- American man with a stable international normalized ratio (INR; 2.6) on a warfarin dose of 50 mg/week. He began using 8 to 10 menthol cough drops per day with a resulting decrease in his INR to 1.6, despite increases in his warfarin dose over a 3-week period.

Five days after discontinuing the cough drops, his INR increased from 1.6 to 2.9. He was subsequently stabilized on a warfarin dose of 40 mg/week. The authors suggest 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 isoenzymes that affect warfarin metabolism. Patients should be alerted to the possibility of this interaction and counseled to let their anticoagulation provider know of any change in OTC or prescription medications.

Genetic Testing to Determine Warfarin Dosing Is Not Cost-Effective in AF
An analysis of studies published using genetic testing to aid in determining initial warfarin doses in patients with nonvalvular atrial fibrillation (AF) showed that such testing is not cost-effective unless the patient is at very high risk for complications from warfarin use.

Genotype-guided dosing resulted in better outcomes, but at a relatively high cost. Overall, the marginal cost-effectiveness of testing exceeded $170,000 per quality-adjusted life-year (QALY). On the basis of current data and cost of testing (about $400), there is only a 10% chance that genotype-guided dosing is likely to be cost-effective (<$50,000 per QALY). Further analysis of the data revealed that for genetic testing to cost less than $50,000 per QALY, it would have to be restricted to patients at high risk for hemorrhage or meet the following criteria: prevent greater than 32% of major bleeding events, be available within 24 hours, and cost less than $200.

Currently, the turnaround time for these tests is 5 to 10 days (depending on the laboratory). With appropriate warfarin monitoring, patients who have genetic mutations are likely to be identified based on their response to initial therapy. Additionally, careful monitoring of the international normalized ratio (INR) allows the clinician to identify and assess the impact of several other important variables on the INR that are not identified with genetic testing. Such variables include smoking habits, use of alcohol, other medical conditions, exercise routines, medications, and routine vitamin K intake.

Potential Interaction Between Pomegranate Juice and Warfarin

An August 2009 case report in Pharmacotherapy warns of a potential interaction between warfarin and pomegranate juice. The report describes a 64-year-old woman who had been on a stable warfarin regimen for 9 months prior to her referral to an anticoagulation clinic. Her international normalized ratio (INR) began to fluctuate 2 to 4 months prior to her referral.

During an education session, she mentioned that she had started drinking pomegranate juice in the past 6 months. The clinic pharmacist researched the interaction and found that pomegranate juice has inhibitory effects on CYP3A and CYP2C9 activity. The CYP2C9 inhibition could have explained the new instability in this patient’s INR. The patient required an increase in her warfarin dosage after she stopped drinking the pomegranate juice. This finding is consistent with what would be expected if the CYP2C9 inhibition was removed.

The patient was not rechallenged with pomegranate juice, so the interaction cannot be definitively proven. It is important to be aware of the possibility, however, so patients can be counseled about reporting all dietary changes. Often, patients do not think about changes in beverages as a “dietary change,” so anticoagulation providers might consider asking specific questions about beverages, given the rising popularity of pomegranate juice. â– 

Dr. Garrett is manager, Outpatient Clinical Pharmacy Programs, at Mission Hospitals in Asheville, North Carolina.

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