Many Common Drugs in Dermatology are Light, Temperature, or Moisture-Sensitive

M.D. Langner, MD and H.I. Maibach, MD
Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA

ABSTRACT

Photosensitivity is defined as responsiveness to light exposure. For many common dermatologic drugs, proper storage conditions are essential for maintaining drug activity. Degradation and loss of activity can occur with exposure to light, temperature, and/ or moisture. For example, ketoconazole degrades after 24 hours of light exposure. In this article storage guidelines for common dermatology drugs are provided. We suspect that drug degradation is common due to improper storage and that improved patient instruction regarding storage will reduce degradation and alleviate some of the danger associated with improper storage and usage patterns.

Key Words: drug storage; drug degradation; light sensitive; moisture sensitive; temperature sensitive

Light can change the properties of different materials and products, and the number of drugs found to be photochemically unstable is steadily increasing. We define “photosensitivity” as the response that a compound shows to light exposure and includes not only degradation reactions, but also other processes, such as the formation of radicals, energy transfer, and luminescence.¹ Most are familiar with the traditional brown medicinal flask or the white pillbox; these offer adequate protection for most drug products during storage and distribution. Indeed, proper storage conditions are essential for the efficacy of many common dermatologic drugs. In modern hospital pharmacies, drugs are often stored in unit-dose containers on an open shelf. In many cases, the protective market pack is removed; the inner container can be made of transparent plastic materials that offer little protection toward UV and visible radiation. The unprotected drug can then be exposed to fluorescent tubes and/or filtered daylight for several weeks or months before it is finally administered to the patient.

Drug efficacy depends on its stability, pH, correct chemical composition, and potency. Preservation of these characteristics require that many commonly used dermatologic drugs be kept in light-, temperature-, or moisture-free storage conditions. Indeed, itraconazole and erythromycin base are sensitive to all ³ conditions. The most common consequence of drug photodecomposition is loss of potency with concomitant loss of therapeutic activity. Although less common, even less severe degradation can lead to problems. Adverse effects due to the formation of minor degradation products during storage and administration have been reported.² In general, 2 aspects of drug photostability must be considered: in vitro and in vivo stability.¹ Even if a drug product is shown to be photochemically inert, in the sense that it does not decompose during exposure to light, it can still act as a source of free radicals or form phototoxic metabolites in vivo.¹ Epstein and Wintroub suggested that patients who take certain dermatologic drugs and subsequently become exposed to light may develop phototoxic drug metabolites.³

Call for Renewed Vigilance in the Proper Storage of Drugs

Table 1 lists some commonly used dermatologic drugs that have special storage requirements; the general storage guidelines that follow provide an easy way to remember which drugs require special attention. The table was generated using The Pharmacopeia of the United States of America, 31st revision,⁴ Physicians’ Desk Reference at www.pdr.net,⁵ European Pharmacopeia,⁶ and British Pharmacopoeia 2007.⁷ An in-depth treatise on the effects of temperature, light, and moisture is provided by Rubinstein.⁸ Actual rates of degradation are not listed in these references, however, as this information is difficult to obtain because studies have not been done to determine degradation rates; most available information about degradation comes from studies that analyze the activity of the medicine.

Rates of Degradation

Studies with ketoconazole have shown that photodegradation occurs after 24 hours of UV light exposure.⁹ Following this, ketoconazole degradation products will peak at 4 minutes with high-resolution gas chromatography, while ketoconazole alone normally peaks at 6 minutes without the 4-minute degradation product peak. Acyclovir activity decreases after exposure to moisture, but the resulting rate of decline is unknown. Likewise, while terbinafine is light-sensitive, we only know that light exposure reduces its activity, although the activity loss-rate is also unknown.

Finally, expiration dates are used because the more time that passes from the initial issuance of the drug to the time when the drug is used will lead to degradation, not only because of its inherent activity, but also because of light exposure. In one Sudanese study, there was a 55% usage rate of old, unfinished drugs.10 Patients need clear instructions about the fact that old medications should be discarded or replaced once the expiration date passes. They should understand that it is not a cost-savings to use expired drugs, because they may not be effective and may even be harmful if degradation leads to the formation of toxic metabolites. Likewise, patients should receive clear storage instructions to avoid exposure to light, moisture, and temperature. While overworked doctors, nurses and pharmacists sometimes give hurried instructions, it is most important that patients be given clear directions.

For example, when patients are prescribed antibiotics, they should always be advised to complete the entire course of treatment. Despite these instructions, patients may not comply, assuming that the drug is no longer needed when they feel better and they may save any remaining medication for another time. This practice has led to the growth of drug-resistant strains of bacteria.^11-14 In other cases, unknowingly taking antibiotics previously associated with allergic symptoms can cause an allergic reaction.¹⁵

General Storage Guidelines

1. Clarithromycin extended-release tablets: preserve in wellclosed containers, protected from light. Store at 25°C, excursions permitted between 15°C, and 30°C.


2. All erythromycin preparations should be packaged and stored in tight containers.


3. Tetracycline hydrochloride should be packaged and stored in tight, light-sensitive containers.


4. Ketoconazole should be packaged and stored in wellclosed containers.


5. Acyclovir should be packaged and stored in tight containers at room temperature, protected from light and moisture.


6. Isotretinoin capsules should be packaged and stored in tight containers, protected from light, and stored at room temperature in a dry place.

Conclusion

The pharmacist receives training on appropriate drug labeling with respect to temperature, light, and humidity. Unfortunately, little literature exists that covers patientstored drug stability in well-lit, humid, non-air-conditioned areas. We suspect that drug degradation may be routine. Improved patient instruction may alleviate some of the danger associated with improper storage and usage patterns.

References

1. Tønnesen HH. Photostability of drugs and drug formulations, 2nd ed. Boca Raton, FL:CRC Press (2004).
2. de Vries H, Beijersbergen van Henegouwen GMJ, Huf FA. Photochemical decomposition of chloramphenicol in a 0.25% eyedrop and in a therapeutic intraocular concentration. Int J Pharm 20:265-71 (1984).
3. Epstein JH, Wintroub BU. Photosensitivity due to drugs. Drugs 30(1):42-57 (1985 Jul).
4. United States Pharmacopeia and National Formulary (USP 31-NF 26). Vol 2,3. Rockville, MD: United States Pharmacopeia Convention, pp. 1303, 1786-9, 2084-98, 2301-5, 2479-80, 2488-90, 3359-65 (2008).
5. Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR (2008).
6. European Pharmacopoeia Commission. European Pharmacopoeia.
6th ed. Strasbourg, France: Council of Europe (2007).
7. British Pharmacopoeia. London, UK: The Stationery Office (2007).
8. Duchene D, Vaution C, Glomot F. Cyclodextrins, their value in pharmaceutical technology. In: Rubinstein MH, editor. Pharmaceutical Technology - Drug Stability. Chichester, NY: Halsted Press;Ellis Horwood, pp. 9-23 (1989).
9. Staub I, Cruz AS, Pinto T, et al. Determinação da segurança biológica do xampu de cetoconazol: Teste de irritação ocular e avaliação do potencial de citotoxicidade in vitro. Revista Brasileira de Ciencias Farmaceuticas 43:301 (2007).
10. Yousif MA. In-home drug storage and utilization habits: a sudanese study. East Mediterr Health J 8(2-3):422-31 (2002 Mar-May).
11. World Health Organization: WHO model prescribing information. Geneva: World Health Organization (2001).
12. MayoClinic.com. Antibiotics: Use them wisely. At: http://www.mayoclinic.com/health/antibiotics/FL00075. Last accessed Dec 2008.
13. MD Consult. Antibiotic Resistance. At: http://www.mdconsult. com/das/patient/body/110084196-2/0/10062/15492.html. Last accessed Dec 2008.
14. American College of Physicians. Antibiotic Resistance. At: http://www.acponline.org/patients_families/disease_ conditions/antibiotic_resistance. Last accessed Dec 2008.
15. Karch AM, Karch FE. When it’s time to clean out the medicine cabinet. Am J Nurs 102(2):23 (2002 Feb).

In this issue:

1. Onychomycosis: Therapy Directed by Morphology and Mycology
2. Many Common Drugs in Dermatology are Light, Temperature, or Moisture-Sensitive
3. Update on Drugs and Drug News - February 2009