Room-temperature Storage of Medications Labeled for Refrigeration

Abstract

Purpose: Data regarding the recommended maximum duration that refrigerated medications available in hospital pharmacies may be stored safely at room temperature were collected and compiled in a tabular format.
Methods: During May and June of 2006, the prescribing information for medications labeled for refrigeration as obtained from the supplier were reviewed for data addressing room-temperature storage. Telephone surveys of the products' manufacturers were conducted when this information was not available in the prescribing information. Medications were included in the review if they were labeled to be stored at 2-8 °C and purchased by the pharmacy department for uses indicated on the hospital formulary. Frozen antibiotics thawed in the refrigerator and extemporaneously compounded medications were excluded. Information was compiled and arranged in tabular format. The U.S. Pharmacopeia's definition of room temperature (20-25 °C [68-77 °F]) was used for this review.
Results: Of the 189 medications listed in AHFS Drug Information 2006 for storage in a refrigerator, 89 were present in the pharmacy department's refrigerator. Since six manufacturers were unable to provide information for 10 medications, only 79 medications were included in the review. This table may help to avoid unnecessary drug loss and expenditures due to improper storage temperatures.
Conclusion: Information regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled.

Introduction

The U.S. Pharmacopeia's Med-marx medication-error-reporting system has received nearly 1000 reports involving errors associated with refrigerated medications.^[1] Many of these reports were a result of nursing staff not realizing that certain medications required refrigeration. Subsequent errors involved delayed administration of medications to patients and inappropriate storage of expensive medications (e.g., epoetin alfa). Recommendations based on a review of these errors suggested displaying a table on the outside of the refrigerator door listing common refrigerated items for that particular unit.^[1]

Inappropriate vaccine storage has been implicated in numerous reports of vaccine-related adverse events.^[2] For example, two days after receiving a pneumococcal polysaccharide vaccination that had not been refrigerated, a patient developed dizziness, racing heart, jerking of the limbs, and "pins and needles" from head to toe, resulting in a persistent and significant disability. In another case, a patient developed a cluster of 20 painful and itchy vesicles on an erythematous base on the midposterior lateral forearm after receiving varicella vaccine that was not properly refrigerated.^[2]

In 1975, Wolfert and Cox^[3] recognized that pharmacists were often asked about the stability of refrigerated medications that are accidentally stored at room-temperature. However, because product labeling was insufficient regarding room-temperature stability and pharmacists were not routinely able to predict stability based on the physicochemical properties of the medications, the authors surveyed manufacturers about room-temperature storage of selected medications labeled for refrigeration. This information was then compiled into a table for use as a guide to control drug storage within the authors' institution.

In 1983, Vogenberg and Souney^[4] compiled a similar table describing the acceptable duration of storage of medications labeled for refrigeration when refrigerated (2-8 °C) after 24 hours of storage at room-temperature, when stored in a cool place (8-15 °C), and when stored at room-temperature (15-30 °C).

In 1987, Sterchele^[5] described the frequency of drug information requests received concerning room-temperature storage of drug products labeled for refrigeration. The author reported that this information was not easily retrievable and often incomplete and compiled an updated table to supplement the previously available information on the topic. Only 22 of 36 manufacturers replied with information about 39 products, and most manufacturers did not provide data for storage in "a cool place," as it was unrecognized as a method for storage. In 1990, Dalton-Bunnow and Halvachs^[6] updated the available data. In 2006, Cobos Campos et al.^[7] compiled written information from drug manufacturers about the room-temperature storage of 83 medications labeled for refrigeration. This information was limited by the fact that it was collected outside of the United States and published in the Spanish medical literature.

The objective of this study was to provide an updated table of the maximum acceptable duration that medications labeled for refrigeration may be stored at room-temperature.

Methods

During May and June of 2006, we reviewed the prescribing information for medications labeled for refrigeration as obtained from the supplier for data addressing room-temperature storage. The U.S. Pharmacopeia's definition of room-temperature (20-25 °C [68-77 °F]) was used.^[8]

Telephone surveys and follow-up inquiries of the products' manufacturers were conducted when information about room-temperature storage was not available in the prescribing information.

Medications were included in the review if they were labeled to be stored at 2-8 °C and purchased by our pharmacy department for uses indicated on the hospital formulary. Frozen antibiotics thawed in the refrigerator and extemporaneously compounded medications were excluded. Information was compiled and arranged in tabular format.

Results

Of the 189 medications listed in AHFS Drug Information 2006 for storage in a refrigerator,^[9] 89 were present in our pharmacy department's refrigerator and were included in this review. The information for 34 of these medications (38%) was obtained from the official prescribing information. A total of 44 manufacturers were contacted and asked to provide the relevant information for the remaining 55 medications (62%). Since 6 manufacturers were unable to provide information for 10 medications, information was compiled and tabulated for 79 medications ( Table 1 ).

Discussion

The table is limited by our hospital pharmacy's formulary; however, our purpose was to update the current literature.

The table is intended for use as a guide when medications labeled for refrigerated storage are inadvertently exposed to room-temperature. This may occur during routine excursions, power outages, compressor failures, natural disasters, and inadvertent storage at room-temperature if the need for refrigeration is unknown. According to the manufacturers surveyed, the medications included in the table may be returned to the refrigerator within the time period listed without affecting stability or expiration date. This table may help to avoid unnecessary drug loss and expenditures due to improper storage temperatures.

Although a full discussion of methods of stability information is beyond the scope of this article, the methods to evaluate temperature-related storage recommendations for medications are required to be reported to the Food and Drug Administration as part of current good manufacturing practices.

While recommended temperature-related storage data were easily retrievable from the medications' prescribing information, the effects of temporary excursions from refrigeration were not always addressed. Retrieving this information from each manufacturer was complicated by prolonged response times, lack of available data, and the inability of some manufacturers to release the information for legal reasons.

Conclusion

Information regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled.