Drug Storage and Stability - 25/08/11
Stability data on drug products are generally derived from studies done under controlled and artificial environmental conditions. However, drug stability in the setting of real-world variable climate conditions is more difficult to study. Only limited research in this area has been published.
This appendix reviews the data currently available on drugs likely to be carried in field and expedition medical kits. The list is extensive, and for smaller expeditions only a fraction of the more critical medications will be required. However, it is also useful for medical professionals who are setting up field hospitals and clinics in suboptimal climate conditions.
Most medications, as indicated in the following sections, have strict temperature ranges at which they should be maintained to assure their potency. Other factors, including light, humidity, and packaging, also influence the shelf life and sterility of a drug. Strong packaging is critical; if a parenteral drug (packaged in a syringe for ready use) is frozen, the drug may be fully potent, but its sterility may have been lost due to hairline cracks in the plastic caused by freezing. Polyvinyl (plastic) containers often used to package drugs may affect product stability. Glass containers, although considered the most inert of storage vessels, may leach alkali and associated decomposition products into the product, thereby initiating chemical reactions that alter drug potency. The inclusion of preservatives in the drug formulation and the actual processes used by the manufacturer may also make products more or less resilient in the face of prolonged storage. Thus, for most of the drug products listed, stability and sterility cannot be guaranteed if products are stored under conditions deviating from those recommended by the manufacturer. The following guide should be supplemented with drug packaging information provided by the manufacturer.
EXPIRATION DATESDrug manufacturers usually set shelf life by calculations of drug potency under ideal conditions. Shelf life is the time during which the potency is expected to be greater than or equal to 90% of the drug’s initial potency at manufacture. Shelf life assumes that the drug is maintained at optimal storage conditions. Extremes of temperature, high humidity, loss of integrity of original packaging, and exposure to light can all potentially shorten this period. In addition, some drugs may actually have decreased bioavailability after exposure to non–temperate climate conditions. This is because the rate of dissolution is often the rate-limiting step in the absorption of many medications taken by mouth, and further complicates a drug’s pharmacodynamics. High heat and humidity conditions can affect the rate of product dissolution.
STORAGE OPTIONSUnfortunately, the wilderness setting leaves few options for the storage of drugs under ideal environmental conditions. Vehicular storage, while a convenient option in many cases, can expose drugs to temperature variations much greater than ambient conditions unless efforts are actively undertaken to control the temperature swings. This is illustrated in a 2003 study by Helm and colleagues.5 This 2003 pre-hospital medical study quantified the temperature stresses placed on medications in real mission conditions, including rescue helicopter, ambulance, and transport vehicles during 2 months of summer and 2 months of winter. This was performed in a moderate climatic zone (southern Germany). Recorded temperatures varied from −13.2° C to +50.6° C (8.2° F to 125° F). The recommended maximum storage temperature (+25° C [77° F]) was exceeded in all rescue vehicles (33% to 45% of total exposure time), whereas the recommended minimum storage temperature (0° C [32° F]) only fell short 19% of total exposure time. The daily maximum temperature ranged from 19° C (66° F) in winter to 32.9° C (91° F) in summer. These results show that even in a moderate climatic zone, drugs used in pre-hospital vehicles are significantly influenced by temperature stress; furthermore, these results recommend the use of temperature-controlled drug boxes.
Vehicle-powered cooling devices are a viable option in this setting, assuming the vehicle battery is kept charged. Styrofoam or plastic cooler boxes with cooling packs are an adequate storage modality as well but can be somewhat cumbersome on a trekking expedition. Many small coolers are available, however, so medications that require cooling or darkness can be separated out and stored in a manageable small unit.
Portable refrigeration units may be required for long-term storage of products that require strict constant refrigeration, especially if ice is not going to be readily available. Many of these units require electricity and are equipped with enough insulation to prevent their contents from becoming too warm in the event of a power failure for up to several hours if unopened. A few products also exist that can also run on natural gas or kerosene, thereby ameliorating the problem of unreliable electricity supply. Systems with passive cooling, such as ice packs, tend to be lighter, whereas those with active cooling systems can be much heavier (over 50 kg [110 lbs]).
An important consideration in choosing these devices and other, simpler ice coolers is the thickness of their foam insulation and the durability of the surrounding encasement, often constructed of metal or plastic. The amount of snow or ice used for cooling varies depending on the ideal temperature storage range for each drug. A thermometer should be kept inside the box near the medications and monitored regularly.
Portable generators can weigh as little as 12 kg (26.5 lbs), but careful consideration of the power needs for the expedition should be made prior to purchase, as the weight to be carried can increase quickly with increased power requirements. Additional weight is also incurred for the generator’s power source. Power types include batteries, liquid fuel, and solar panels. Solar has the added advantage of being lightweight and renewable. There are several solar products that are ideal for portable heating and cooling equipment and for recharging car batteries.
Many medications suggest storage at “room temperature” of 15° to 30° C (59° to 86° F). For these, standard refrigeration is not appropriate. Electric medication storage boxes are available and for long expeditions are a reasonable solution. A more inexpensive lightweight solution for short-term medication storage problems is to use chemical heat packs or instant cold packs (both widely commercially available) to heat or cool the ambient temperature inside a cooler. Confirm appropriate temperature range with a thermometer. Chemical heat packs can produce up to 150° F (70° C) of heat and last for several hours, so do not place them directly on the medication. Otherwise, the medication may “cook”; also avoid direct ice application to avoid inadvertent freezing. Routinely re-check the medication thermometer.
Whatever storage container is chosen should be waterproof, and, if possible, air-tight. Consider adding a desiccant to decrease damage from humidity. Many medications need to be protected from light, so if the box is transparent, place it in a dark bag. Place loose tablets in a bottle or blister pack to avoid breakage. If product packaging is discarded to save space, retain the product information leaflet and dosing information in a plastic bag.
There is no formal consensus on the long-term effect of humidity and other climate changes on many medications. Anticipate that any gel-encased medication, such as a suppository, may melt in high humidity and/or warmth, and become challenging to use even if it is still medically active.
After longer trips, consider replacing medications with a fresh stock.
“REAL WORLD” DRUG STABILITY RESEARCHMost medication stability data is obtained from lab tests in very controlled artificial environments. The data in this appendix are primarily from these sources. However, there exists a small body of literature addressing “real world” drug storage and usage. Some of the best research that more closely mimics field use in wilderness settings comes from the pre-hospital emergency medical services (EMS) literature.
Particular attention has been focused on medications commonly stocked in pre-hospital EMS vehicles. Understandably, these are the medications most likely to undergo degradation as a result of prolonged or intermittent exposure to more extreme climate conditions. See the Helm study discussed earlier for quantified temperature variations in EMS transport vehicles.5
Valenzuela and colleagues8 performed a study that monitored 23 pre-hospital medications, using gas chromatography and mass spectrometry, for degradation over the course of a typical summer in Tucson, Arizona. The medications studied were:
After being exposed to temperatures ranging from 28° C to 39° C (82.4° F to 102.2° F) in paramedic storage containers, only two of the studied medications were found to have significant chemical changes. Most notably, isoproterenol lost 11% of the parent compound over the course of the 4 weeks. Its degradation products may be similarly active, but this cannot be assumed. Volumes administered in the field may therefore contain lower than the expected dose. Epinephrine was also affected. The buffer used to maintain the epinephrine solution’s pH was degraded, leading to a decrease in the pH of the solution. However, there was no increase in degradation products of the actual epinephrine component. Nifedipine capsules melted in this study, but the medication itself was found to be stable to heat over the course and conditions of the study period.
A later experiment by Church and colleagues3 found that epinephrine is significantly degraded by heat even before if exhibits the characteristic dark brown color change normally associated with its degradation by oxidation.
Gottwald and colleagues4 studied pre-hospital stability of diazepam and lorazepam. Injectable solutions were stored for up to 210 days in clear glass syringes in three conditions: refrigerated at 4° C to 10° C (39.2° F to 50° F), ambient temperature of 15° C to 30° C (59° F to 86° F), and oven-heated at 37° C (98° F). High-performance liquid chromatography was performed at 30-day intervals. After 210 days, the reduction in diazepam concentration was 7% refrigerated, 15% at ambient temperature, and 25% heated. The reduction in lorazepam concentration was 0% refrigerated, 10% at ambient temperature, and 75% heated. Diazepam retained 90% of its original concentration for only 30 days of on-ambulance storage, whereas lorazepam retained 90% of its original concentration for 150 days. The decrease in lorazepam concentration correlated with an increase in the maximum ambient temperature in San Francisco. These results suggest that diazepam and lorazepam can be stored on ambulances. When ambient storage temperatures are 30° C (86° F) or less, the authors of this study suggest that ambulances carrying these medications should be restocked every 30 to 60 days. When drug storage temperatures exceed 30° C (86° F), more frequent stocking or refrigeration is required.
Johansen and colleagues6 reviewed the effects of extreme temperatures on the chemical structure of four advanced cardiac life support (ACLS) drugs: atropine sulfate, lidocaine hydrochloride, epinephrine, and naloxone hydrochloride. The temperatures used were −20° C, +70° C (−4° F, +158° F), and a combination of the two; these were compared with room temperature controls. These temperature extremes occurred over a period of 48 hours, with four 4-hour-long temperature spikes/troughs. This extreme temperature variation did not seem to affect the chemical structures of these medications. However, the actual bioactivity of the drugs was not tested.
Carrasco and colleagues7 recently reviewed the physical, chemical, and sterility characteristics of previously prepared saline infusions stored in ambulances. They hoped to determine how long they remained in optimum condition. A total of 8028 cultures were performed. Colonization was present in only 1.7% of cultures; only two had more than 5 colony-forming units (CFUs) per mL. This study suggested that there was no difference between “recently prepared” saline infusion solutions and those “previously prepared” and exposed for 24, 48, or 72 hours. This assists with practical real-world constraints of preparation.
Bartfield and colleagues1 investigated the shelf life of buffered lidocaine. It was prepared 7 days, 1 day, and just before use, and compared to a control solution. They found that there was no significant difference in the extent or duration of anesthesia between the different preparation times.
Brown and colleagues2 recently wrote a review of the last 15 years of pre-hospital literature on this topic. They noted that the evidence is clear that EMS medication storage is not consistent with the United States Pharmacopoeia (USP) definition of controlled room temperature. However, the actual impact on medication stability and potency remains unclear and needs more study to determine the extent of the problem and to develop and validate appropriate solutions.
DRUG STABILITY INFORMATIONThe drug stability data on the following drugs and other medical products are nearly always based on studies done in controlled environmental conditions. It is often difficult to ascertain whether a drug product can be safely used after storage under conditions other than those specified by the manufacturer.
As mentioned previously, the question of stability of drug products pertains not only to the drug itself but also to the container in which it is packaged. If, for example, a parenteral drug packaged in a syringe for ready use is frozen, the drug itself may be fully potent, but the sterility of the product may be lost due to hairline cracks from freezing of the syringe.
Thus, for most of the drug products listed, stability and sterility cannot be guaranteed if stored under conditions other than those recommended by the manufacturers.
Slight variations in packaging and formulation between brands may influence the drug’s stability. The following guide should be supplemented with drug packaging information provided by the manufacturer.
If the medication is annotated with an asterisk (*), please see the section on “Real World” Drug Stability Research for additional related information. Please note, however, that any deviation from the manufacturer’s recommendations is the choice of the treating medical professional and is neither condoned nor approved by the authors of this chapter or text.
Medications are listed by their generic names. Where trade names are given, no endorsement of a particular product is implied unless explicitly stated.
By pharmaceutical convention, “room temperature” is defined as between 15° C and 30° C (59° F and 86° F) and “controlled room temperature” is defined as between 20° C and 25° C (68° C and 77° F).
Availability in the United States is subject to Food and Drug Administration (FDA) and Drug Enforcement Agency (DEA) regulations and annotated as OTC (over-the-counter), Rx (prescription required), DEA Schedule (S II to S IV), or NA (not available in the United States).
Acetaminophen Tablets, Elixir, and Suppositories (OTC)Store at room temperature and definitely below 40° C (104° F). Avoid freezing, as stability after freezing is unknown. Not known to be light sensitive. Keep suppositories refrigerated below 27° C (81° C).
Acetaminophen with Codeine Tablets and Elixir (S III)Store at room temperature and definitely below 40° C (104° F). Do not refrigerate or freeze. Protect from light and moisture.
Acetaminophen with Hydrocodone Tablets (S III)Store at room temperature and definitely below 40° C (104° F). Do not refrigerate or freeze. Protect from light and moisture.
Acetazolamide Tablets, Sustained-Release Capsules, Injection, and Oral Formulation (Rx)Store tablets at room temperature; store capsules at controlled room temperature.
Oral formulation: a studied extemporaneous oral formulation of acetazolamide 25 mg/mL in a 1 : 1 mixture of Ora-sweet, Ora-plus, and in cherry syrup (diluted 1 : 4 with simple syrup) was stable at 94% of initial concentration for up to 60 days. Temperatures tested were 5° C and 25° C (41° F and 77° F), and the solutions were protected from light.
Store powder for injection at room temperature. Manufacturer labeling states that the reconstituted drug is stable for 12 hours at room temperature and for 3 days if refrigerated (36° F to 46° F). Other research, however, has demonstrated 90% potency for 1 week at room-temperature conditions, 4 weeks when refrigerated, and 8 weeks when frozen (admixed with 50 mL D5W, 100 mL sodium chloride injection, 50 mL Lactated Ringer’s Injection, or 45 mL Lactated Ringer’s Injection with 5 mL sodium bicarbonate 5%). Do not freeze if combined with Lactated Ringer’s with sodium bicarbonate, as the solution becomes turbid. Do not administer if discoloration, cloudiness, or particulate matter is observed.
Acetic Acid Solution (OTC)Store in airtight containers at controlled room temperature. Protect from light.
Albuterol Tablets, Syrup, and Inhaled Formulations (Rx)Tablets and syrup: store between 2° C and 25° C (36° F and 77° F). Protect tablets from excessive moisture. Refrigeration of syrup can improve taste.
Aerosol inhalers: store at room temperature. Do not expose to excessive temperatures (49° C, 120° F) for more than 1 to 2 days due to explosive danger of the chlorofluorocarbons (CFCs). Do not puncture or incinerate aerosol containers.
Inhalation solution and capsules for inhalation: store between 2° C and 30° C (36° F and 86° F). Inhalation solution is light yellow to clear; discard if discolored.
Aloe Gel, Ointment, Laxatives (OTC)Topical: Aloe vera has been used for burns, wounds, and as an antipruritic. Pharmacologically it is composed of substances capable of producing topical anesthesia, bactericidal activity, and increased local microcirculation, but actual therapeutic capability is not clear. Lotions are for external use only. Product stability in extremes of temperature is not well studied.
Laxatives: aloe acts as a stimulant laxative if taken internally due to anthraquinone glycosides. Aloe laxatives (e.g., Nature’s Remedy) should be stored at room temperature in airtight containers. Avoid humidity and temperatures over 38° C (100° F).
Aluminum Acetate Otic and Topical Preparations (OTC)Otic solution: a clear colorless liquid comprised of acetic acid 2% in aqueous aluminum acetate solution. Store below 30° C (86° F) but protect from freezing.
Topical solution: stable virtually indefinitely, but partially used irrigation solutions have high potential contamination rates. Label extemporaneously prepared solutions with a 7-day expiration date, which is consistent with the shelf life recommended by the manufacturer.
Amiodarone Tablets and Vials (Rx)Store tablets and vials for intravenous (IV) administration at room temperature. Protect both from light during storage, but IV form need not be protected from light during infusion itself. Note that dosing studies were performed using polyvinyl chloride (PVC) tubing. The use of other plastic tubing may affect dosing, as amiodarone IV has been found to leach out plasticizers. This effect is exacerbated by higher drug concentrations and lower flow rates than recommended by the manufacturer.
Antacids (OTC)Avoid freezing aluminum hydroxide or milk of magnesia products. If frozen, many antacids separate into water and gel layers upon thawing. Freezing is not known to affect the therapeutic value of the product, but anecdotally it affects taste and prevents reformation of the emulsion, even with shaking.
Aspirin Tablets, Oral Solution, and Suppositories (OTC)Tablets: aspirin is stable in dry air but gradually hydrolyzes to salicylate and acetate and gives off a vinegar odor. Most manufacturers recommend storage at room temperature.
Oral solution: an extemporaneous oral solution can be made from a commercial buffered effervescent tablet (Alka Seltzer) with 90 mL of water.
Suppositories: store between 2° C and 15° C (36° F and 59° F).
Atenolol Tablets (Rx)Store at controlled room temperature, 20° C to 25° C (68° F to 77° F). Dispense in well-closed, light-resistant containers.
Atropine Injection (Rx)*Store at room temperature and protect from light. Atropine sulfate 1 mg/mL solutions packaged in Tubex (0.5 mL and 1 mL) have been shown to be stable for 3 months. Atropine methylnitrate 10 mg/mL solutions are stable for 6 months when stored in dark bottles at room temperature. Inspect solution prior to administration for the presence of particulate matter, cloudiness, or discoloration and discard if present.
Azithromycin Tablets, Capsules, Suspension, and Injection (Rx)Tablets and capsules: store below 30° C (86° F).
Suspension: single dose packets should be refrigerated if possible (5° C to 30° C, 41° F to 86° F) and, if reconstituted with 60 mL of water, should be used immediately. Discard multiple dose suspension after 10 days.
Injection: store under 30° C (86° F). After preparation, it is stable for 24 hours at room temperature and for 7 days if refrigerated.
Bacitracin Topical (OTC) and Injection (Rx)Topical: store at room temperature. If in ointment form, it is stable but rapidly inactivated in water. Calamine, benzocaine, and zinc oxide have been combined with bacitracin without affecting its stability. If in aqueous solution, it must be refrigerated and is stable for only 1 week due to oxidation.
Injection: store sterile powder for injection between 2° C and 15° C (36° F and 59° F) and protect from light. Solution is stable for 1 week after reconstitution if refrigerated.
Bismuth Subsalicylate Tablets and Suspension (OTC)Store at room temperature and avoid heat greater than 40° C (104° F). Suspension should not be frozen.
Bretylium Tosylate (Rx)*Store at room temperature. Protect from freezing.
Bupivacaine Injection (Rx)Bupivacaine is a relatively stable drug, but excessive heat or cold decreases its shelf life. Store between 15° C and 40° C (59° F and 104° F). If frozen, may be used after thawing provided the container is completely intact and the solution remains clear. Bupivacaine with epinephrine exposed to light and/or temperatures over 40° C (104° F) for a long period should not be used due to loss of epinephrine effect.
Butorphanol Tartrate Injection and Nasal Solution (S IV)Store below 30° C (86° F). Protect from light and do not freeze. Inspect parenteral drug for particulate matter or discoloration prior to use and discard if present.
Calcium Chloride Injection (Rx)*10% solution: drug pH is altered significantly if frozen or exposed to temperatures over 40° C (104° F). The product should be considered unusable if either occurs.
Ceftriaxone Injection (Rx)Store powder for injection at or below 25° C (77° F). Protect from light. The color of solution ranges from light yellow to amber, depending on concentration, length of storage, and diluent. Once mixed, intramuscular (IM) and IV solutions remain >90% potent for up to 10 days if refrigerated at 4° C (39° F). Potency is affected by diluent, concentration, and temperature. IM and IV preparations may maintain >90% stability for as little as 1 or 3 days, respectively, at room temperature. If reconstituted with 5% dextrose or 0.9% sodium chloride solution and then frozen at −20° C (−4° F), preparations have been stable for 26 weeks in PVC or polyolefin containers. Thaw at room temperature before using. Unused thawed solutions should be discarded. Do not refreeze. Ceftriaxone may be incompatible with other antimicrobials; do not mix.
Cephalexin Capsules, Tablets, and Oral Suspension (Rx)Capsules and tablets: store at room temperature.
Suspension: stable after reconstitution for up to 14 days if refrigerated, ideally between 2° C and 8° C (36° F and 46° F). Keep tightly closed. Shake well before using.
Charcoal, Activated (OTC)Sealed aqueous suspensions may be stored for at least 1 year in tightly sealed container. For longest shelf life, keep in well-sealed metal or glass containers.
Ciprofloxacin Capsules, Tablets, Suspension, and Injection (Rx)Oral: store tablets at room temperature, and store capsules and suspension diluent below 25° C (77° F), but do not freeze. Discard unused suspension after 14 days. Protect from light.
Injection: store flexible containers between 5° C and 25° C (41° F and 77° F) and IV infusion vials between 5° C and 30° C (41° F and 86° F). Avoid temperatures over 40° C (104° F) and protect from light. When injection is diluted for injection, it is stable for 2 weeks at either room temperature below 30° C (86° F) or when refrigerated between 2° C and 8° C (36° F and 46° F). Do not freeze.
Cyclopentolate Hydrochloride Ophthalmic Solution (Rx)Store between 5° C and 25° C (41° F and 77° F). Keep in tightly capped airtight container.
DEET-Containing (N,N-Diethyl-Meta-Toluamide, Diethyltoluamide) Insect Repellents (OTC)Store at room temperature and in airtight containers. Avoid exposures of propellant cans to temperatures of 49° C to 54° C (120° F to 130° F) due to explosion danger. Do not store or use near fire or open flame. Avoid contact with plastic or rayon. DEET may be toxic internally, so store away from other consumables.
Dermabond (2-Octyl Cyanoacrylate) Topical Skin Adhesive (Rx)Store below 30° C (86° F), protect from moisture, direct heat, and incidental crushing. The product should be used immediately after crushing the glass ampule, as it will not flow freely after a few minutes.
Dexamethasone Injection (Rx)*Injection: a clear, colorless to light yellow solution that is sensitive to light and extremes of temperature. Do not store at high temperature for long periods. It maintains full potency for 6 months at 40° C (104° F) and up to 3 months at 50° C (122° F). Do not use after freezing and protect from light except while injecting.
Dextroamphetamine Tablets, Elixir, and Capsules (S II)Tablets: store in well-sealed containers at room temperature.
Elixir and extended-release capsules: store in tight, light-resistant containers, below 40° C (104° F), preferably at room temperature. Do not freeze elixir.
Dextrose Oral (OTC) and Injection (Rx)*Oral: store in well-airtight containers.
Injection: store 50% parenteral dextrose below 25° C (77° F). Do not freeze or expose to extreme heat. Do not use if cloudy. Discard unused portions.
Diazepam Tablets, Oral Solution, Suppositories, and Injection (S IV)*Tablets and elixir: store at controlled room temperature. Protect from moisture and avoid freezing.
Oral solution: store at controlled room temperature. Protect from moisture and avoid freezing. Available as both regular dose and concentrated solution requiring calibrated dropper for accurate dosing. Do not prepare and store doses for future use.
Suppository: store at controlled room temperature and protect from moisture.
Injection: store at controlled room temperature. If frozen, diazepam tends to flocculate and precipitate. Rewarm with warm water and, if no precipitate is visible, the product may be used. Do not inject if solution is cloudy, contains particulate matter, or is darker than slightly yellow.
Digoxin Injection (Rx)Digoxin has been shown to be stable at room temperature for 3 months in Tubex cartridges. Protect from light and store between 15° C and 25° C (59° F and 77° F). Use diluted injection immediately. This product is compatible with most IV infusion fluids.
Diltiazem Capsules, Oral Solution, and Injection (Rx)Capsules: store at room temperature. Protect from excess humidity.
Oral solution: 12 mg/mL solution prepared in Ora-Sweet, Ora-Sweet SF, Ora-Plus, or in a 1 : 4 mixture of cherry syrup and simple syrup was more than 92% potent for up to 60 days at either 5° C or 25° C (41° F or 77° F). In another study, 1 mg/mL solution prepared from dextrose, fructose, mannitol, and sorbitol (but NOT lactose) remained potent for a minimum of 50 days at 25° C (77° F).
IV solution: should preferably be stored between 2° C and 8° C (36° F and 46° F), without freezing, but may be stored at room temperature for up to 1 month, then discarded.
Diphenhydramine Tablets, Elixir (OTC), and Injection (Rx)*Store at room temperature if possible in airtight containers. Tablet, elixir, and injection (10 mg/mL) forms are stable after freezing, but injection containers should be checked for cracks or leakage. Protect injection form from light.
Domeboro Astringent and Otic Solutions (OTC)Astringent solution: do not cover compress or wet dressing with plastic; allow to breathe.
Otic solution: a clear colorless liquid. Store below 30° C (86° F). Avoid freezing.
Dopamine Hydrochloride Injection (Rx)*Store at room temperature and protect from light. Brief exposure to temperatures of 40° C (104° F) is tolerated, but excessive heat should be avoided. Do not freeze. Do not use if there is yellow, pink, purple, or brown discoloration of the solution, as this indicates decomposition. The diluted form is stable for injection for at least 24 hours after dilution.
Doxycycline Capsules, Tablets, Syrup, Suspension, and Injection (Rx)Oral formulations: store capsules, tablets, syrup, and suspension below 30° C (86° F), preferably at room temperature. Store delayed-release capsules between 15° C and 25° C (59° F and 77° F). Suspension is stable for 2 weeks after reconstitution if stored at room temperature.
Injection: frozen, reconstituted 10 mg/mL solution for injection in sterile water is stable for 8 weeks when stored at −20° C (−4° F). After thawing, excess heating is not recommended. Do not refreeze. Protect from light. The infusion should be completed within 6 to 48 hours (brand and diluent dependent) if not refrigerated.
Epinephrine Injection (Salts and Solutions) (Rx)*Store at controlled room temperature and protect from light and air. Avoid freezing.
Heat above 40° C (104° F) and exposure to light may inactivate the product. Oxidation causes a color change to pink, then brown. Do not use if discolored, cloudy, or contains precipitate.
Erythromycin Tablets, Suspensions, Topical, and Injection (Rx)Oral formulations: erythromycin estolate and erythromycin ethylsuccinate (EES 200 and 400) liquid suspensions maintain their potency for 14 days at room temperature. Refrigeration maintains optimal taste. Tablets should not be crushed.
Topical: stable for 2 years when stored at room temperature. Gel and pledgets should be stored at room temperature while ointment should be stored under 27° C (81° F). An extemporaneous topical solution made from tablets with hydroalcoholic vehicle as a 2% solution was stable for 60 days at 25° C (77° F). A 2.7% preparation in E-Solve was stable for 4 months when refrigerated between 4° C and 8° C (39° F and 46° F).
Injection: stable at room temperature in dry form. Reconstituted IV solution should be used within 8 hours after preparation or within 24 hours if refrigerated. Drug stability may be maintained up to 2 weeks if refrigerated but carries significant risk of contamination. Solution may be frozen for 30 days and is stable if used within 8 hours of thawing under refrigeration conditions. Do not refreeze thawed solution.
Estazolam Tablets (S IV)Store below 30° C (86° F). Stable for 3 years after date of manufacture.
Fluocinolone Acetonide Ointment and Shampoo (Rx)Ointment: store in a tight container below 40° C (104° F), preferably at room temperature. Avoid freezing.
Shampoo: stable for 3 months after extemporaneous formulation.
Furazolidone Tablets and Liquid (NA)Store in light-resistant container. Exposure to strong light may cause darkening. Do not expose to excessive heat. May crush tablets and administer in spoonful of corn syrup.
Furosemide Oral Formulations and Injection (Rx)*Oral, tablets and solutions: store in tightly closed light-resistant container at room temperature. Discard oral solution bottles 60 days after opening. Do not use if discolored.
Injection: protect containers from light. When packaged in Tubex cartridges (2 mL of 10 mg/mL) potency was retained for 3 months at room temperature. If exposed to refrigeration, solution may be used barring evidence of cracking, leaking, or other damage to glass containers. All intact ampules or syringes, when returned to room temperature, should be vigorously shaken to redissolve any constituents that may have crystallized out of solution; stability should not be affected. Do not use if discolored.
Glucagon Injection (Rx)In powder form, glucagon should be refrigerated but is stable at room temperature for several weeks. When diluent is added to powder, the resulting solution may be refrigerated for up to 3 months. Thawing will not affect activity. Cloudy or thick diluent should not be used. Do not use if stored at temperatures greater than 35° C (95° F) for an extended period.
Hydrocortisone Tablets, Suspension, Topical Cream, and Injection (Rx)Oral preparations: store below 40° C (104° F), at room temperature. Protect suspension from light and freezing.
Topical: do not refrigerate.
Injection: do not freeze. Only use reconstituted solutions if clear and discard after 3 days.
Hydromorphone Tablets, Elixir, Suppositories, and Injection (S II)Tablets and elixir: store at room temperature and protect from light.
Suppositories: keep refrigerated.
Injection: store at room temperature. Avoid refrigeration/freezing as precipitation or crystallization can occur, but product may be redissolved at room temperature without affecting stability. A slight yellowish discoloration does not affect potency. Polypropylene infusion syringes containing hydromorphone hydrochloride in normal saline were stable for 30 days when stored at 30° C (86° F).
Ibuprofen Tablets (OTC)Store at room temperature and protect from light.
Intravenous Solutions (D5W, D5NS, Etc.)*Effects of freezing these solutions are unknown. Incomplete resolubility, especially with electrolyte-containing solutions, seems a real danger.
Isoproterenol Hydrochloride (Rx)*Store at room temperature 15° C to 30° C (59° F to 86° F). Protect from light. Do not use if solution is pinkish to brownish in color.
Ketoconazole Shampoo and Tablets (Rx)Shampoo: store at or below 25° C (77° F). Protect from light.
Oral tablets: store at room temperature. Protect from moisture.
Lacriserts (Hydroxypropyl Methylcellulose) Topical Ocular Solution (Rx)Store drops at room temperature in airtight containers. Protect from freezing.
Levofloxacin Tablets and Injection (Rx)Tablets: store at room temperature and protect from light.
Injection: store concentrate at room temperature and protect from light. Reconstituted form can be stored up to 3 days if kept below 25° C (77° F), 14 days if refrigerated between 2° C and 8° C (36° F and 46° F), and up to 6 months if frozen. Thaw at room temperature or under refrigeration conditions but do not thaw by immersion in water or by microwave. A mild yellow/greenish color is normal and not indicative of contamination or breakdown. However, do not use if particulate matter or other discoloration is noted.
Lidocaine Injection (Rx)*Lidocaine is a relatively stable drug, but excessive heat or cold decreases its shelf life. Store between 15° C and 40° C (59° F and 104° F). If frozen, it may be used after thawing provided the container is completely intact and the solution remains clear. Lidocaine with epinephrine exposed to light and/or temperatures over 40° C (104° F) for a long period should not be used due to loss of epinephrine effect.
Lidocaine/Epinephrine/Tetracaine (LET) Topical (Rx)Anesthetic solution stored in amber glass (light-shielding) containers is stable for 4 weeks at approximately 18° C (65° F) and for 26 weeks if refrigerated (4° C, 39° F).
Lindane (Gamma-Hexachlorocyclohexane) Lotions and Shampoo (Rx)The lotion and shampoo become thick when frozen, but do not lose effect. The effect of high temperatures is unknown. Protect from light. Spray should not be exposed to temperatures below −2° C (28° F) or above 54° C (129° F).
Loperamide Hydrochloride Capsules (OTC)Store at room temperature. Do not mix oral solution with other solvents.
Lorazepam Tablets, Oral Solution, and Injection (S IV)*Tablets: store at room temperature and protect from moisture.
Oral solution: refrigerate between 2° C and 8° C (36° F and 46° F). Protect from light.
Injection: refrigerate between 2° C and 8° C (36° F and 46° F). Protect from light. Do not use if cloudy, discolored, or if particulate matter is present.
Mannitol Injection (Rx)Injection form (5% to 25% solution): store at controlled room temperature. Solutions of 15% or higher may crystallize at temperatures below 25° C (77° F) but will resolubilize when warmed to 70° C to 80° C (158° F to 176° F) in a water bath. A reheated solution must be allowed to cool to body temperature prior to administration. Microwaves had been used to reheat mannitol, but extreme caution is indicated as explosions of ampules have been reported. Sterility cannot be guaranteed if frozen.
Meperidine Hydrochloride Oral Solution and Injection (S II)Oral solution: store at room temperature. Protect from moisture, light, and freezing.
Injection: store at room temperature. Protect from moisture, light, and freezing. If frozen, injection form may be used after thawing if the solution shows no signs of precipitation or cloudiness and if the ampules or vials show no signs of cracking or leaking.
Metoprolol Oral Preparations and Injection (Rx)*Store at 25° C (77° F). Excursions permitted to 15° C to 30° C (59° F to 86° F). Do not freeze. Protect from moisture. Store in a tight, light-resistant container.
Midazolam Oral Solution and Injection (S IV)Oral solution: an oral solution of 2.5 mg/mL, made from injectable midazolam and a flavored, dye-free syrup, maintained >90% of the original concentration throughout a 56-day trial period at temperatures of 7° C, 20° C, and 40° C (45° F, 68° F, and 104° F).
Injection: store in syringes or glass at room temperature and protect from light. Parenteral midazolam of 2 mg/mL (hydrochloride salt) in 0.9% sodium chloride injection was stable in polypropylene infusion-pump syringes at both 5° C and 30° C (41° F and 86° F) for 10 days. A 3 mg/mL concentration maintained at least 90% stability for 1 week when stored in disposable polypropylene syringes in 20° C, 32° C, and 60° C (68° F, 90° F, and 140° F). Midazolam 40 mg/L in 0.9% sodium chloride was stable when protected from light at 21° C (70° F) over 24 hours, with no loss in glass or laminate containers and less than 2% loss in PVC bags.
Modafinil Tablets (S IV)Store at controlled room temperature. Not known to be light sensitive.
Morphine Sulfate Injection (S II)*Store at room temperature in airtight containers. Protect from light. When exposed to air, morphine sulfate loses its water and concentration may change, producing higher than expected dosing. Avoid freezing. If freezing occurs, it does not affect potency but may form precipitate. Solution should be colorless to pale yellow. Do not inject if cloudy, discolored, or contains precipitate. May use if precipitate resolubilizes with shaking. Most studies of morphine stability have been limited to 30 days, but one study noted stability after 14 weeks of frozen storage. However, intentional freezing cannot be recommended.
Moxifloxacin Tablets and Injection (Rx)Tablets: store at room temperature and protect from high humidity.
Injection: store premixed flexible containers at room temperature and protect from light. Do not refrigerate, as IV solution tends to precipitate. Do not use if particulate matter or discoloration is noted.
Nalbuphine Hydrochloride Injection (Rx)Store at room temperature and protect from light. Do not use if discolored or contains precipitate.
Naloxone Hydrochloride Injection (Rx)*Store at room temperature and protect from light. Dilute solution prior to use and if not used, discard any solution 24 hours after dilution. Do not save partial doses for future use. Do not administer if discoloration, cloudiness, or precipitate are observed. Protect from freezing and do not use if frozen.
Neosporin Ointment (OTC)Store at controlled room temperature.
Nifedipine Capsules, Tablets, and Injection (Rx)*Capsules: store between 15° C and 25° C (59° F and 77° F) and protect from light.
Tablets: store at room temperature and protect from light.
Injection: store below 25° C (77° F). Ready-to-use infusion retains potency for only 1 hour in daylight and 6 hours in artificial light. Keep in light-sealed container until absolutely ready to use.
Nitroglycerin Sublingual Tablets, Spray, Topical, and Injection (Rx)*Oral preparations: keep sublingual tablets in original glass container, tightly capped. Discard cotton once removed. Store at room temperature. Protect from moisture, heat, cold, and humidity. Discard unused sublingual tablets after 6 months. Translingual spray has guaranteed potency for 4 years from the date of manufacture when stored below 50° C (122° F).
Topical ointment: tube should be kept tightly closed and stored at room temperature.
Injection: nitroglycerin solutions (diluted in 5% dextrose or 0.9% sodium chloride solutions in glass containers) are stable for up to 2 days at room temperature and up to 7 days when refrigerated. Extemporaneous solutions of nitroglycerin in concentrations ranging from 0.035 to 1 mg/mL were stable in glass for up to 70 days at room temperature and for 6 months when refrigerated. Brief exposure up to 40° C (104° F) does not adversely affect the potency or stability of the solution. Do not freeze.
Norfloxacin Tablets and Ophthalmic Solution (Rx)Tablets: store at room temperature and definitely below 40° C (104° F). Store in tightly closed containers.
Ophthalmic solution: store at room temperature and protect from light.
Ofloxacin Tablets, Otic Solution, and Injection (Rx)Tablets: store below 30° C (86° F) in a tightly-closed container.
Otic solution: store at room temperature in airtight container.
Injection: store single-use vials and premixed bottles at room temperature. Store premixed mini-bags at or below 25° C (77° F). Avoid light, freezing, and excessive heat. Brief exposure to 40° C (104° F) has not been shown to damage product.
Penicillin G Procaine Injection (Rx)Should be refrigerated but is stable at room temperatures for 6 months. Higher temperatures increase hydrolysis and decrease potency. May be frozen and retain potency. Solutions prepared for injection are stable are room temperature for at least 1 day and up to 1 week if refrigerated.
Penicillin GK Injection (Rx)Stable in powder form for 2 to 3 years if stored at no greater than 30° C (86° F). Higher temperatures cause decreased potency. Solutions prepared for injection are stable are room temperature for at least 1 day and up to 1 week if refrigerated.
Phenobarbital Injection (S IV)*Store at room temperature and protect from light. Not stable in aqueous solutions. Inspect for precipitate and discoloration before use and do not administer if present.
Phenylephrine Nasal (OTC), Ophthalmic Solution (Rx), and Injection (Rx)Do not use nasal, ophthalmic, or parenteral solutions if brown in color or if there is precipitation. Store parenteral solution at room temperature and definitely below 40° C (104° F). Protect all forms from light and freezing.
Phenytoin Tablets and Injection (Rx)Oral preparations: store at room temperature. Protect from moisture and light.
Injection: store at room temperature. Solution is stable if there is no precipitation or haziness. A precipitate may form when refrigerated or frozen but will dissolve when warmed to room temperature. A faint yellow color has no effect on potency. More stable in normal saline than in 5% dextrose. Infuse within 2 hours of mixing the solution, then discard.
Polysporin Ointment (Rx)Store between 15° C and 25° C (59° F and 77° F).
Potassium Permanganate Astringent Solution (OTC)Diluted form is used to clean wounds, ulcers, abscesses, and dermatoses. Use 0.1% solution in water to be diluted 1 in 10 before use to provide a 0.01% solution. Undiluted potassium permanganate is composed of dark purple or almost black crystals or granular powder and is soluble in cold and boiling water. It is incompatible with iodides, reducing agents, and most organic substances and may be explosive if it contacts organic or other oxidizable substances.
Povidone Iodine Solution (OTC)Do not heat as iodine concentration may decrease due to interaction with dissolved oxygen or may increase due to water evaporation. Store between 37° C and 42° C (99° F and 108° F).
Prednisone Tablets, Oral Solution, and Suspension (Rx)Store at room temperature and definitely below 40° C (104° F). Protect from light using airtight container. A suspension prepared using 50 mg of prednisone powder, 100 mg of sodium benzoate, and a sufficient quantity of simple syrup to bring the volume to 100 mL was stable for 12 weeks at room temperature. Shake well prior to use.
Prochlorperazine Injection, Solution, Tablets, and Capsules (Rx)Store at room temperature in airtight, light-resistant containers. Avoid freezing. Discard discolored solution.
Promethazine Injection, Tablets, Solution, and Suppositories (Rx)Store oral and parenteral products at room temperature. Refrigerate suppositories between 2° C and 8° C (36° F and 46° F). Protect all forms from light and avoid freezing.
Pseudoephedrine and Pseudoephedrine/Triprolidine Tablets and Capsules (OTC)Pseudoephedrine tablets and capsules: store between 15° C and 25° C (59° F and 77° F) in a dry place and protect from light. Should not be crushed.
Triprolidine tablets and capsules: store at room temperature and protect from light.
Sildenafil Tablets (Rx)Store at room temperature.
Simethicone Tablets, Capsules, and Drops (OTC)Store at room temperature in airtight container. Protect from light and freezing.
Sodium Bicarbonate Injection (Rx)*Store 50 mL injection ampules at room temperature. Brief exposure to 40° C (104° F) will not compromise efficacy. Do not freeze and do not use if product has been frozen.
Sodium Sulfacetamide Ophthalmic Solution and Ointment (Rx)Ophthalmic solution: store in a light-resistant container in a cool place, between 8° C and 15° C (46° F and 59° F). Discard if solution darkens to brown.
Ophthalmic ointment: store at room temperature and do not freeze.
Temazepam Capsules (S IV)Store at room temperature in airtight container. Protect from light.
Tetanus Toxoid (Rx)Injection: Toxoid should be refrigerated; however, it remains stable for months when stored at room temperature. Do not freeze and do not use if product has been frozen.
Tetracaine Hydrochloride Ophthalmic Solution (Rx)Protect ampules from light. Refrigerate between 2° C and 8° C (36° F and 46° F) to prevent crystallization and oxidation. Stable for several days at room temperature. If then returned to cool storage, the stability is as labeled by the manufacturer.
Tetracycline Tablets, Topical Solution, and Injection (Rx)Outdated products may cause renal tubular disease.
Tablets: store at room temperature. Protect from moisture or light (product will darken).
Topical: solution prepared with diluent from the manufacturer is stable for 2 months at room temperature.
Injection: reconstituted solutions are stable at room temperature for 12 hours (6 to 12 hours in 5% dextrose in water).
Tolnaftate Topical Antifungal (OTC)Store between 2° C and 30° C (36° F and 86° F). Do not freeze. May solidify at low temperatures but liquefies easily when warmed; its potency is not affected. Aerosol products are under pressure. Do not puncture or place in proximity to heat/flame.
Triazolam Tablets (S IV)Store at room temperature and protect from light.
Trimethoprim/Sulfamethoxazole Tablets, Suspensions, and Injection (Rx)Oral preparations: store tablets and suspensions in a dry place, either between 15° C and 25° C (59° F and 77° F) or at room temperature, depending on the formulation.
Injection: should be used within 4 or 6 hours (depending on dilution in D5W). Injection (16 mg/80 mg per mL) has been shown to maintain greater than 90% stability for over 60 hours when stored in polypropylene syringes. Discard if cloudy or if precipitate is present. Use within 24 hours if using multiple-use vial for injection. Protect from light. Do not refrigerate or freeze.
Verapamil Hydrochloride Tablets and Injection (Rx)*Store at controlled room temperature 15° C to 30° C (59° F to 86° F). Protect from light.
Store extended-release tablets at controlled room temperature 20° C to 25° C (68° F to 77° F).
Dispense oral forms in tight, light-resistant container. Protect from moisture.
Discard any unused amount of parenteral solution.
Zinc Salts (OTC)Zinc oxide (e.g., calamine) is practically insoluble in alcohol and water but dissolves in dilute mineral acids. Store zinc acetate in airtight containers and zinc chloride and sulfate in airtight nonmetallic containers. Zinc sulfate ophthalmic solutions should be stored below 40° C (104° F) in tightly closed or airtight containers. Avoid freezing.
Zolpidem Tablets (S IV)Store at controlled room temperature in airtight container.
© 2007 Mosby, Inc. Tous droits réservés.
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