MANAGEMENT OF DRUG SHORTAGES IN ONCOLOGY PRACTICE

Identifying the major causes of drug shortages and exploring the impact on the overall health care system reveal the complexity of the issue. The impact on oncology may be something as simple as delaying a patient’s chemotherapy for several days until a new shipment of drug is allocated, to something more significant such as omitting a drug from a chemotherapy regimen or using a second-line drug in a chemotherapy regimen without a clear picture of the bearing on a patient’s cancer treatment—or worse, full knowledge that the alternative therapy is suboptimal to the standard-of-care regimen.

Although no evidence-based or guideline-driven method is in general practice for handling drug shortages, the potential sources for error and some methods for managing these shortages are described. However, the particular ways of handling a shortage are entirely dependent on the type of practice setting and the preference of the treating physician(s).

One related issue arising in oncology practice is an increase in medication errors or near-miss medication errors related to nontraditional changes or alterations to standard-of-care regimens. The National Coordinating Council for Medication Error and Prevention (NCC MERP) defines a medication error as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer.”12 A near miss, on the other hand, is defined by the Institute of Safe Medication Practices (ISMP) as a medication error that is captured and corrected by active efforts on the part of the health care team prior to reaching the patient.13 A recently published ISMP survey regarding drug shortages reported that 35% of respondents had been involved in or witnessed a near-miss medication error, 25% responded that an error actually occurred, and 20% claimed the error had a negative impact on the patient.1 Recognizing that a particular drug strength, concentration, or dosage form may be on short supply is important, and health care professionals need to be on the lookout for such confusion. Table 1 outlines some potential causes of medication errors during a drug shortage. All health care professionals who treat oncology patients—from physicians to pharmacists, to nurses—are responsible for ensuring that these types of errors do not occur.


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Although some chemotherapy protocols have available alternatives, clinicians are still faced with the dilemma that not all options have been assessed or researched clinically, and not all chemotherapy regimens or disease states have a viable alternative. Table 2 presents some options or alternatives that resulted from recent chemotherapy drug shortages. The impact on overall survival in patients who were switched from asparaginase (Elspar) to pegaspargase (Oncaspar), 5-fluorouracil (Adrucil, generics) to capecitabine (Xeloda), and leucovorin to levoleucovorin (Fusilev) is unknown. In fact, FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin [Eloxatin, generics]) has been compared with only CapOx/XelOx (capecitabine, oxaliplatin) in randomized clinical trials of colorectal cancer in the metastatic setting;14 however, because of the leucovorin shortage, clinicians were making this switch in the adjuvant setting where no data exist. In addition, significantly more GI toxicity was noted with CapOx/XelOx than with FOLFOX.1 In this example, not only is the overall impact on survival unknown, but additional impacts on patients’ quality of life occurred.

In some cases, head-to-head comparisons of regimens may exist, but concerns about the efficacy or toxicity reported in the results may exist. For example, a direct, randomized comparison of ABVD (doxorubicin [Adriamycin, Doxil, Rubex, generics], bleomycin [Blenoxane, generics], vinblastine [Velban, generics], dacarbazine [DTIC-Dome, generics]) and MOPP (mechlorethamine [Mustargen], vincristine [Oncovin, Vincasar, generics], procarbazine [Matulane], prednisone [Prednisone Intensol, Sterapred, generics]) for Hodgkin lymphoma treatment demonstrated that both regimens were equal in terms of efficacy, but differed in regards to toxicity.15 Patients receiving MOPP experienced significantly more nausea/vomiting, secondary cancers, and sterility compared with patients receiving ABVD. The last two side effects are important considerations in a highly curable disease for which the median age of diagnosis is approximately 25 years, and patients are expected to live 40+ years posttreatment. In other instances, the second-best alternative agent, levoleucovorin (used during the leucovorin shortage), can become scarce as well, usually because of the increased demand. This may force clinicians to resort to using third- and fourth-line regimens to treat patients. Front-line chemotherapy agents are not the only drugs affected either; commonly used supportive medications can be an issue as well (Table 3). Supportive care medications, however, typically have more alternatives and the outcomes are more easily assessed.

CONCLUSION

Overall, drug shortages are frustrating, intricate, and multilayered. The complexity of the manufacturing process, the FDA and its authoritative role, inappropriate use of grey markets, and the economic burden of drug shortages compound the issue further and make the solution to the drug-shortage dilemma seem impossible to attain. Despite the availability of alternatives in most circumstances, the impact on outcomes for oncology patients, for the most part, cannot be characterized and is unknown at this time. However, the multidisciplinary oncology team is charged with the responsibility for continuing to provide the utmost in patient-focused and quality care despite the circumstances surrounding our current drug-supply issues. ONA


Jennifer Tobin is a hematology/oncology clinical pharmacy specialist at the University of Colorado Cancer Center, Aurora, Colorado.


REFERENCES

1. Institute for Safe Medication Practices (ISMP). Special issue: drug shortages national survey reveals high level of frustration, low levels of safety.

ISMP Medication Safety Alert! Acute Care. Published September 24, 2010. http://www.ismp.org/Newsletters/acutecare/articles/20100923.asp. Accessed May 13, 2011.

2. ASHP Expert Panel on Drug Shortages, Fox ER, Birt A, James KB, et al. ASHP guidelines on managing drug product shortages in hospitals and health systems. Am J Health Syst Pharm. 2009;66(15):1399-1406.

3. Slama L. Oncology drug shortage rising. Health Leaders Media Web site. Published February 18, 2011. http://www.healthleadersmedia.com/page-1/ HOM-262817/Oncology-Drug-Shortage-Rising. Accessed May 13, 2011.

4. Tyler LS, Mark SM. Understanding and managing challenges posed by drug shortages. Proceedings of a breakfast symposium held during the 37th annual ASHP Midyear Clinical Meeting; December 9, 2002. http://www.ashp.org/s_ashp/docs/files/DShort_abbott_drug.pdf. Accessed May 13, 2011.

5. Tyler LS, Fox ER, Caravati EM. The challenge of drug shortages for emergency medicine. Ann Emerg Med. 2002;40(6):598-602.

6. Summary of a stakeholders’ meeting on drug shortages convened by the American Medical Association and the American Society of Health-System Pharmacists. Provisional observations of drug product shortages: effects, causes, and potential solutions. Am J Health Syst Pharm. 2002;59(22):2173-2182.

7. Fox ER, Tyler LS. Managing drug shortages: seven years’ experience at one health system. Am J Health Syst Pharm. 2003;60(3):245-253.

8. American Society of Anesthesiologists, American Society of Health System Pharmacy, American Society of Clinical Oncology, Institute for Safe Medication Practices. Drug Shortages Summit Summary Report. November 5, 2010; Bethesda, MD. http://www.ashp.org/drugshortages/summitreport. Accessed May 13, 2011.

9. Li EC. Coping with drug shortages. National Comprehensive Cancer Network Web site. http://www.nccn.org/about/news/ebulletin/2011-02-07/drug_shortages.asp. Accessed May 13, 2011.

10. Thompson CA. Drug shortage broaches ethics of buying in excess. Am J Health Syst Pharm. 2009;66:610-611. doi:10.2146/news090032.

11. Frequently Asked Questions. Institute for Safe Medication Practices Web site. http://www.ismp.org/faq.asp. Accessed May 13, 2011.

12. What is a medication error? National Coordinating Council for Medication Error Reporting and Prevention Web site. http://www.nccmerp.org/aboutMedErrors.html. Accessed May 12, 2011.

13. ISMP survey helps define near miss and close call. ISMP Medication Safety Alert! Acute Care. http://www.ismp.org/Newsletters/acutecare/articles/20090924.asp. Accessed May 13, 2011.

14. Cassidy J, Clark S, Diaz-Rubio E, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26(12):2006-2012.

15. Canellos GP. Can MOPP be replaced in the treatment of advanced Hodgkin’s disease? Semin Oncol. 1990;17(1 suppl 2):2-6.

16. Current drug shortages. US Food and Drug Administration Web site. http://www.fda.gov/drugs/drugsafety/drugshortages/ucm050792.htm. Accessed May 13, 2011.