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Probable Warfarin-Simvastatin Interaction

Head of Section, RELIS Medicines Information Centre, Health Region South, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

Peder Johansson, MD

Hospital Physician, Department of Medicine, Akershus University Hospital, Lørenskog, Norway

Espen Molden, MScPharm PhD

Scientist, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo

Reprints: Dr. Westergren, RELIS Medicines Information Centre, Health Region South, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway, fax 00 47 23 07 53 90, tone.westergren{at}rikshospitalet.no

OBJECTIVE: To report and discuss a case of fatal cerebral hemorrhage following a switch from atorvastatin to simvastatin in a patient taking warfarin.

CASE SUMMARY: An 82-year-old white female was admitted to the hospital because of an international normalized ratio (INR) value greater than 8, which was detected at a routine follow-up visit to monitor warfarin therapy. Four weeks earlier her lipid-lowering therapy had been switched from atorvastatin 10 mg daily to simvastatin 10 mg daily. She had been treated with 2.5 mg of warfarin daily for almost 30 years due to episodes of deep venous thrombosis and lung embolism. Her INR had been stable within the treatment range (2.0-3.5) for more than 2 years before the INR increase. Upon hospitalization, she was given 5 mg of vitamin K orally. A few hours later she lost the feeling and movement of her right arm and a computed tomography scan showed major bleeding in the left cerebral hemisphere. She died the following day.

DISCUSSION: One study has shown a lack of interaction between warfarin and atorvastatin. In comparison, 3 studies have shown significant increases (10-30%) in warfarin effect and/or reductions in dose requirement after starting concomitant simvastatin treatment. The interaction mechanism between simvastatin and warfarin is not known but is possibly associated with reduced elimination of warfarin. Use of the Naranjo probability scale showed that the likelihood of warfarin-induced INR increase following the switch to simvastatin was probable.

CONCLUSIONS: Atorvastatin and simvastatin appear to differ in their potential to interact with warfarin. Clinicians should be aware of the interaction risk when starting simvastatin treatment in patients on warfarin therapy.

Key Words: atorvastatin, hemorrhage, simvastatin, warfarin

Published Online, June 12, 2007. www.theannals.com, DOI 10.1345/aph.1K167