Not Too Hot, Not Too Cold…
Just Right:
Temperature Stability and
Storage of Medications 

By Nancy Pietroski, PharmD, FAWM, WEMT, CTH 

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It makes sense for medications to be stored at room temperature or “conditions of civilization” (1) – but of course not all medications may be stable at 20º-25ºC (68º-77ºF). Or they may be susceptible to moisture, light, or other conditions that aren’t the perfect environment in which the pharmaceutical company that manufactured them originally tested them for stability. 

First, let’s think of how you store your medications at home. Do you keep them in the original bottle from the pharmacy or do you throw all your pills together in one bottle so you don’t have to open different bottles every day? Do you correctly store medications that have to be refrigerated in the fridge? Do you even know at what temperature your refrigerator is set? If you have medications mailed to you, do they sit in your mailbox on a 100-degree day until you get home from work? Or are they buried in the snow on your porch step on a 5-degree day? Are they stored in your medicine cabinet in the bathroom – which gets hot and steamy every time a shower is taken? Are they sitting on the kitchen windowsill so you won’t forget to take them, exposed to direct sunlight?


In wilderness and remote environments, which may be perfect for an exhilarating experience but not for drug storage, conditions may be much more extreme. Are you trekking in the Mongolian desert toting medications, whether for yourself or for an expedition? Climbing a 20,000-foot peak? Did you pack the medications in your checked-in luggage so they’re sitting in the freezing non-pressurized cargo area in the plane? Are your pills rolling around in a bottle on a rocking dive ship?

HOW DO YOU KNOW AT WHAT TEMPERATURE  A MEDICATION NEEDS TO BE STORED?

First, here’s the conversion between °C and °F:

°F = °C x 1.8 + 32

°C = (°F-32) x 5/9 (0.56)

The recommended storage range is pretty simple for over-the-counter drugs: it’s printed on the container or blister pack:


However, for prescription drugs, unless they are dispensed in the original manufacturer’s container, the amber or white plastic bottle the pharmacy dispenses does not usually contain the proper storage range unless the drug needs to be stored at a particular temperature, for example, refrigerated, protected from light, etc.


The best way to find the correct storage temperature for prescription drugs is in the manufacturer’s prescribing information (found on the drug company’s website, the PDR, or a copy that is provided by the pharmacy). A typical “Storage and Handling” section for a room temperature product reads:

Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] 

A typical section for a refrigerated product reads: 

Store refrigerated at 2 to 8°C (36 to 46°F). 

If appropriate, it may also contain:

Do not freeze. Protect from light.

Fortunately, not many products need to be frozen, which presents another level of complexity in environments outside the home or healthcare facility.

CONDUCT OF STABILITY STUDIES BY THE MANUFACTURER AND SIMILARITIES TO THE WILDERNESS ENVIRONMENT

Drug manufacturers adhere to stability testing guidelines put forth by the United States Pharmacopeial Convention (USP), International Conference on Harmonization (ICH), or the World Health Organization (WHO). Drugs are tested for stability under long-term and accelerated storage conditions, and compatibility with the container they will be shipped in. If temperature controls are needed during distribution of the drug (i.e., “cold chain”) and these are not met, for example if there are transport delays and extreme temperatures, then a temperature excursion occurs, possibly putting the drug at risk of losing its efficacy or even becoming toxic. (2)

One can think of transport of a drug in a wilderness medicine or travel setting as somewhat analogous to this production, testing, and distribution of the drug by the manufacturer (“supply chain”). 

Below are environmental conditions to which a drug can be exposed during transport by the wilderness traveler:


WHAT HAPPENS TO DRUGS WHEN THEY ARE NOT STORED IN PROPER CONDITIONS?

The following table illustrates different types of environmental conditions and what can happen to medications, with an example of a medication that would be used in wilderness medicine.

The following are other medications that may be used in wilderness or travel medicine and possible effects of the environment on stability.

MEDICAL LITERATURE ON STABILITY OF MEDICATIONS IN EMS, WILDERNESS, OR EXTREME ENVIRONMENTS

EMS

Brown and Campagna did a very nice review in EMS World about 10 years ago on storage of medications in the EMS environment. They included the table below with guidelines from the USP for storing medications in EMS vehicles and ambulances. (4)

Extreme Environments

Kupper et al published the most complete review in the medical literature of stability of drugs in extreme environments entitled “Drugs and Drug Administration in Extreme Environments”, which was published in the Journal of Travel Medicine in 2006. (1) Please refer to this article for specific stability studies on emergency drugs in extreme conditions.

Epinephrine and Freeze-Thaw Cycles

Beasley et al studied the impact of freeze-thaw cycles on the stability of epinephrine in autoinjectors. (5) It was found that epinephrine concentrations increased after multiple freeze-thaw cycles, but still remained within standards. However, the authors recommended that the drug be stored under appropriate conditions when possible.

TEMPERATURE MANAGEMENT IN EXTREME ENVIRONMENTS

Jason Luthy published a neat study in Wilderness Medicine Magazine entitled “Temperature Management of Medication in Remote Environments.” (6) 

In the study, Longleaf Wilderness Medicine tested various temperature conditions in wilderness outings. These included the ambient temperature, temperature inside a first aid kit, at the base layer of the test subject (using the LogTag data logger), with an insulated thermos, next to a chemical heat pack, or an evaporative cooling towel. The study found that body heat provided the most consistent temperature (between both cold and hot extremes) and one suggestion for carrying medication on a wilderness trip was to put it into a soft bag then into an avalanche beacon harness. This might be ideal for medications such as an EpiPen, which has the following storage recommendations:

Protect from light. Epinephrine is light sensitive and should be stored in the carrier tube provided to protect it from light. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature). Do not refrigerate. 

Space 

And don’t forget the hapless Mark Watney in “The Martian,” but more importantly, astronauts on real space missions. What happens to drugs in the environment of space? Du et al. conducted stability studies on 35 medications stored on the International Space Station vs. Earth. (7) Environmental effects in space include higher radiation levels, vibration, and decreased gravity. Many medications were found to be less stable in space due to the active ingredient itself and the container in which it was packaged.

Medication Transport in the Wilderness

Please refer to the excellent Wilderness Medicine Magazine article by Tatyana Havryliuk and Tracy Cushing for tips on packing and traveling with medications on expeditions and wilderness trips. 


An especially useful table contained the following information:

Ways to protect your medications from the elements

Protect from heat

• Use ice packs and insulated containers as temporizing measures

• Submerge in cold water or snow in a water tight bag

• Refrigerate if available, consider solar power

• Maximize protection from sunlight and humidity as listed below

Protect from cold

• Keep product indoors or inside tent, inside sleeping bag

• Use chemical heat packs and insulating containers as temporizing measure

Protect from humidity

• Ensure ventilation (open windows)

• Ensure circulation (create breeze, use fan to circulate fresh air if available)

• Use air tight caps

• Store in zip-lock or water proof bags to protect from accidental exposure to moisture

Protect from sunlight

• Use opaque dark bottles

• Do not take product into direct sunlight

• Store in shade

Air travel

• Check with manufacturer of oxygen concentrator and other products of concern to make sure they can be used “in-flight”

• Most inhalers are safe to be used during flight

 

Posted on May 11, 2016

Nancy Pietroski, PharmD, FAWM, WEMT, CTH 

Nancy Pietroski, PharmD, FAWM, WEMT, CTH is a clinical pharmacist from Telford, PA. She is also an Emergency Medical Responder for the Pennsylvania DOH. She has been a member of the National Ski Patrol (NSP) for 14 years and is an alpine patroller at Bear Creek Mountain Resort, and a Nordic ski and bike patroller at Valley Forge National Historical Park. She is an instructor and course coordinator for Outdoor Emergency Care, the NSP's training program for emergency medical care and transportation for outdoor enthusiasts. She has been an author and editor for Wilderness Medicine Magazine for 7 years, and is currently Senior Editor of the magazine. As well, she is an author and Associate Editor of ISTM's Travel Medicine News. She has extensive experience in infectious diseases, drug information, medical writing and medical training, and has written numerous scientific and continuing education articles. She has travelled to many countries throughout the world on whitewater kayaking and trekking trips, and in addition to skiing, also loves reading, mountain biking, animals, and yoga.

REFERENCES: 

(1) Kupper TEAH, Schraut B, Rieke B, Hemmerling A-V, Schoffl V, Steffgen J. 

Drugs and Drug Administration in Extreme Environments. J Travel Medicine 2006;13(1):35-47.

(2) Ammann C. Stability Studies Needed to Define the Handling and Transport Conditions of Sensitive Pharmaceutical or Biotechnological Products. AAPS PharmSciTech 2011;12:4:1264-1275

(3) Coleiro Daphne. Storage of Medicines and Medical Devices. 2012

https://www.um.edu.mt/__data/assets/pdf_file/0016/153160/Storage_of_Medicines_and_Medical_devices.pdf

(4) Brown LH, Campagna JD (Mar 1, 2005) Medication Storage in the EMS Environment: Understanding the Science and Meeting the Standards http://www.emsworld.com/article/10324134/medication-storage-in-the-ems-environment-understanding-the-science-and-meeting-the-standards

(5) Beasley H, Ng P, Wheeler A, Smith WR et al. The Impact of Freeze-Thaw Cycles on Epinephrine. Wilderness Environ Med 2015; 26(4):514-9.

(6) Luthy J. Temperature Management of Medication in Remote Environments. http://wildernessmedicinemagazine.com/1170/Temp-Management-of-Medication

(7) Du B, Daniels VR, Vaksman Z, Boyd JL et al. Evaluation of Physical and Chemical Changes in Pharmaceuticals Flown on Space Missions. The APPS Journal. 2011;13(2): 299-308.


ADDITIONAL READING: 

Briese B, Marmer M. Drug Stability in the Wilderness (Appendix). In: Auerbach PS. Wilderness Medicine. 6th Ed. Philadelphia, PA; Elsevier Mosby; 2012: 2205-2214.

Goodyer L. Travel Medical Kits. In: Keystone JS, Freedman DO, Kozarsky PE, Connor BA, Nothdurft HD. Travel Medicine. 3rd Ed. Elsevier Saunders; 2013: 63-66.