Possible Effect of Refrigeration of Warfarin
Possible Effect of Refrigeration of Warfarin
A 43-year-old African-American woman taking warfarin for prevention of ischemic stroke experienced fluctuating international normalized ratio (INR) values over 8.5 months; no cause could be identified. After reading a pharmacy information sheet that accompanied a warfarin refill, she reported that she had been refrigerating her warfarin because her other drugs had been "sticking together." She then was instructed to store her warfarin at room temperature. During the 8.5 months she had been refrigerating her warfarin, 80% of her INR values had been outside her goal range versus 37.5% during 9 months of storage at room temperature. A MEDLINE search and communication with the drug's manufacturer provided no information regarding storage of warfarin outside the temperature range of 59-86°F and resultant changes in potency of the drug. Because of potential fluctuation in anticoagulation control, patients should be reminded to store their warfarin at room temperature.
Warfarin is a narrow-therapeutic index drug, and small changes in systemic concentration may lead to large changes in pharmacodynamic response. Response to warfarin can be affected by many factors that influence its pharmaco-kinetics and pharmacodynamics, such as drug interactions, vitamin K intake, compliance, changes in health status, and alcohol intake. However, little is known about the effect of storage temperatures on the stability and potency of warfarin. The package insert states that warfarin should be stored at 59-86°F; no information is provided regarding storage at temperatures cooler than 59°F or the effect this may have on potency of the drug (Ludwig CL, DuPont Pharmaceuticals, personal communication, June 25, 2001).
Fluctuations in anticoagulation control, measured by the international normalized ratio (INR), can occur frequently due to alterations in the aforementioned factors. However, due to detrimental effects of thrombosis or bleeding with subtherapeutic or supratherapeutic INR values, respectively, patients are educated to be aware of and to minimize any confounding factors. Yet sometimes INR values change even with no apparent confounding factor that may affect anticoagulation.
A 43-year-old African-American woman taking warfarin for prevention of ischemic stroke experienced fluctuating international normalized ratio (INR) values over 8.5 months; no cause could be identified. After reading a pharmacy information sheet that accompanied a warfarin refill, she reported that she had been refrigerating her warfarin because her other drugs had been "sticking together." She then was instructed to store her warfarin at room temperature. During the 8.5 months she had been refrigerating her warfarin, 80% of her INR values had been outside her goal range versus 37.5% during 9 months of storage at room temperature. A MEDLINE search and communication with the drug's manufacturer provided no information regarding storage of warfarin outside the temperature range of 59-86°F and resultant changes in potency of the drug. Because of potential fluctuation in anticoagulation control, patients should be reminded to store their warfarin at room temperature.
Warfarin is a narrow-therapeutic index drug, and small changes in systemic concentration may lead to large changes in pharmacodynamic response. Response to warfarin can be affected by many factors that influence its pharmaco-kinetics and pharmacodynamics, such as drug interactions, vitamin K intake, compliance, changes in health status, and alcohol intake. However, little is known about the effect of storage temperatures on the stability and potency of warfarin. The package insert states that warfarin should be stored at 59-86°F; no information is provided regarding storage at temperatures cooler than 59°F or the effect this may have on potency of the drug (Ludwig CL, DuPont Pharmaceuticals, personal communication, June 25, 2001).
Fluctuations in anticoagulation control, measured by the international normalized ratio (INR), can occur frequently due to alterations in the aforementioned factors. However, due to detrimental effects of thrombosis or bleeding with subtherapeutic or supratherapeutic INR values, respectively, patients are educated to be aware of and to minimize any confounding factors. Yet sometimes INR values change even with no apparent confounding factor that may affect anticoagulation.
