Pomegranate Juice Elevated International Normalized Ratio in a Patient on Warfarin: a Case Report

Abstract

The aim of this study was to evaluate and report a case of elevated international normalized ratio (INR) in a patient taking pomegranate juice. A case of one, 72- year-old Thai woman had taken warfarin due to aortic valve replacement with a tissue valve. Her underlying diseases included diabetes mellitus type II, hypertension and dyslipidemia; and medication history was comprised of aspirin, volglibose, bisoprolol, metformin, glicazide, simvastatin and digoxin. She denied smoking and alcohol drinking. In one of her regular visits on appointments for routine examination of INR. The INR from this visit was 7.58 which was elevated from previous INR of 2.99 examined 2 months ago. She had taken 1.5 mg/day for 1 month before the elevated INR. There was no clinical sign/symptom which indicated abnormal bleeding despite the elevated INR. The patient was interviewed for drug utilization and adherence including daily consumption by a pharmacist who notified daily intake of 2 glasses (about 50 ml) of pomegranate juice during the past 2 months. Drug-drug and drug-disease interactions were reviewed by medical team and found to be non relevant to the elevated INR. The mechanism of drug–herb interaction between warfarin and pomegranate juice is unclear. In-vivo and in-vitro studies indicated Punica granatum extract showed the inhibitory activity against CYP3A4 and had a report of decrease platelet aggregation. This case report represents that pomegranate juice may be synergistic effects to warfarin as same as previous reports. Therefore, pharmacists should advise and closely monitor the patients who use pomegranate juice with warfarin.