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Double Trouble

Jerry H. Gurwitz, MD | September 1, 2005
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Case Objectives

  • Appreciate the incidence of adverse drug events in older persons
  • List preventative measures that can be used to minimize medication errors in this population
  • Encourage patients to take an active role in their pharmaceutical care

Case & Commentary: Part 1

A 79-year-old man with diabetes mellitus was admitted to the hospital with hypoglycemia. His medication regimen included Glucovance, a combination of metformin and glyburide. Upon discharge, the patient was instructed to stop the Glucovance and to begin monotherapy with Glucophage (metformin).

The case begins with the patient having been admitted to the hospital with hypoglycemia. Since the patient’s prior diabetic history is not described, we do not know whether he was started on these two oral hypoglycemic agents as his initial treatment. If so, this may have placed him at increased risk for this adverse drug event (ADE). Starting therapy in an elderly patient with a single agent is generally a safer strategy, and many patients will achieve adequate control of blood glucose with monotherapy alone.

Although most medication errors do not result in injury, the extensive use of medications by the geriatric population places many older patients at risk. A recent study assessed the incidence and preventability of ADEs among older persons in the ambulatory clinical setting.(1) Interestingly, hypoglycemic agents were among the most common causes of preventable ADEs in this study. The overall rate of ADEs was found to be 50 per 1000 person-years of observation, with a rate of 14 preventable ADEs per 1000 person-years. If these findings hold true for all Medicare enrollees, then more than 1,900,000 ADEs—more than a quarter of which are preventable—occur each year among the 38 million Medicare enrollees. Approximately 180,000 of these ADES would be life-threatening or fatal, and more than 50% of these may be preventable. Most errors associated with preventable ADEs occur at the prescribing and monitoring stages of pharmaceutical care; however, problems with patient adherence are cited as a contributing factor in more than 20% of ADEs that occur in the ambulatory setting.

Case & Commentary: Part 2

A few weeks after his hospitalization, the patient presented to the emergency department (ED) with mental status changes. A fingerstick glucose test was 40 mg/dL. According to the patient, his only medication was Glucophage. The patient recalled an occasional skipped meal. He did not recall taking extra doses. Upon review of his medication bottles, the ED staff found that he was actually still taking Glucovance, not Glucophage.

This case highlights many important opportunities to improve medication safety in older patients, including (i) the “start low and go slow” philosophy when initiating and intensifying a therapeutic regimen in the geriatric patient, (ii) the importance of anticipating confusion from sound-alike medications, (iii) the responsibility of the health care team to provide careful instructions to patients about their medications, and (iv) the need to improve communication and information transfer at times of transitions in care between different health care settings—in this instance, discharge from hospital to home.

Of particular relevance to this case, the combination drug product containing both metformin and glyburide is marketed under the name Glucovance, and metformin alone is marketed under the name Glucophage. Although Glucovance may offer advantages in simplifying use of a multi-drug regimen with a single pill, here, that added convenience may have resulted in confusion for this patient about the nature of his treatment regimen. The patient may have mistakenly believed that he was already being treated with a single drug (single pill = single drug), and this misunderstanding may have been compounded by the similarity in drug names. The Institute of Medicine report “To Err is Human” included a recommendation that the Food and Drug Administration require pharmaceutical companies to test proposed drug names to identify and remedy potential sound-alike and look-alike confusion with existing drug names.(2) [Go to related commentary]

Despite its clear importance, the issue of patient adherence to a prescribed regimen has received very little attention in the literature concerning preventing ADEs. Most studies of preventable ADEs have been conducted in hospital and long-term care settings, where all aspects of pharmaceutical care are presumed to be supervised; generally the patient is given little, if any, responsibility for medication administration or monitoring. In contrast, in the ambulatory setting, such responsibilities do extend to the patient and/or family members and therefore require new levels of patient and family education by physicians, nurses, or pharmacists. This process is often compromised by hurried interactions or haphazard processes, leading to the provision of incomplete or confusing information. This can be particularly risky for elderly patients on complex medication regimens.

Safety issues may arise soon after hospital discharge due to discontinuities in care or communication.(3) In one U.S. teaching hospital, 19% of discharged medical patients experienced an adverse event within a month, one-third of which were considered preventable.(4) Another third were judged “ameliorable” because their severity could have been reduced with better monitoring or earlier response to the problem. Another study conducted in a Canadian teaching hospital yielded similar findings. In this study, 17% of the post-discharge adverse events required rehospitalization and 3% resulted in death.(3) Of particular note, this study identified type 2 diabetes mellitus as an independent predictor of a post-discharge adverse event. Some specific examples of drug-related adverse events occurring after hospital discharge are listed in the Table.(3)

Although research data are limited, a number of recommendations for preventing medication errors in older patients can be inferred from observational studies. Medication reconciliation is a “process of identifying the most accurate list of all medications a patient is taking—including name, dosage, frequency, and route—and using this list to provide correct medications for patients anywhere within the health care system.”(5) Medication reconciliation is particularly important at the time of hospital discharge. Each time a patient moves from the hospital setting to the ambulatory, rehabilitation, or long-term care setting, providers should review with the patient and/or responsible family member previous medication lists alongside the list of medications prescribed at discharge and reconcile any differences. This process should take place both prior to leaving the hospital and again promptly after transition to the new setting of care. When an error related to problems in medication reconciliation is identified, it is useful to systematically analyze its root causes, using an instrument such as the Medication Discrepancy Tool (Figure) produced by the Care Transitions Program at University of Colorado at Denver and Health Sciences Center.

Interventions involving multidisciplinary teams that are initiated in the hospital or ED setting and that follow the patient into the community can prevent medication errors and other drug-related problems.(6) Instruments designed to enhance the identification of discrepancies between the medications prescribed in acute care settings and what elderly patients actually take after discharge may be particularly useful.(7) The community pharmacist’s role in preventing medication errors in elderly patients may be helpful but has not been adequately examined.(8) Given the potential importance of this intervention, it should be formally assessed.(9)

The Institute for Safe Medication Practices (ISMP) is a nonprofit organization with a mission to provide error-reduction strategies to the health care community, policy makers, and the public. ISMP advises patients to insist that their physicians inform them of the generic and brand names of each of their medications, as well as each medication’s spelling and specific indication.(10) Explaining that some pills contain multiple pharmacotherapeutic agents must be considered a critical part of this activity, as emphasized by this case. ISMP has also recommended that patients schedule a “brown-bag check-up” (11) with their primary care physician, a dedicated time to review all current prescribed and over-the-counter medications, which they should bring to the doctor’s office.

Adverse medication events are common, and the elderly are at particular risk due to need for multiple medications and complexity of dosing regimens. Providers should review all new medications with patients and family members, with specific emphasis on possible points of confusion, and perform medication reconciliation at all transitions of care. Patients should have a comprehensive understanding of their own medication regimen. Such efforts may have prevented the hypoglycemic event described in this case.

Take-Home Points

  • To limit risk for adverse drug effects, “start low and go slow” when increasing the dose and complexity of medication regimens in the elderly. However, every effort must be taken to provide elderly patients with the full benefits of an optimal therapeutic regimen, including the use of adequate drug doses and multi-drug regimens when required.
  • The prescribing physician should be vigilant for sound-alike and look-alike confusion with generic and brand drug names. Areas of potential confusion should be pointed out to the patient.
  • Patients should also be made aware if a single pill contains more than one medication.
  • Elderly patients on hypoglycemic agents may be at special risk for preventable ADEs and should be monitored closely in the context of any change in the treatment regimen.
  • Each time a patient moves from the hospital setting to the ambulatory, rehabilitation, or long-term care setting, providers should review with the patient and/or responsible family member previous medication lists alongside the list of medications prescribed at discharge and reconcile any differences.
  • Multidisciplinary interventions to reduce medication errors, involving a strong role for the pharmacist, should be considered for use as elderly patients transition from one clinical setting to another.
  • The increased involvement of older persons in their own pharmaceutical care has the potential to be particularly beneficial in reducing medication errors. Patients must insist that their physicians inform them of the generic and brand names of each of their medications, as well as the spelling of and indications for each. A periodic “brown-bag check-up” with their primary care physician may serve to reduce the risk for medication misunderstandings and ADEs.

Jerry H. Gurwitz, MD The Dr. John Meyers Professor of Primary Care Medicine Chief of Geriatric Medicine University of Massachusetts Medical School


1. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289:1107-1116. [ go to PubMed ]

2. Kohn LT, Corrigan JM, Donaldson MS, eds. To Err is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000.

3. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital. CMAJ. 2004;170:345-349. [ go to PubMed ]

4. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse events affecting patients after discharge from the hospital. Ann Intern Med. 2003;138:161-167. [ go to PubMed ]

5. Midelfort L. Medication Reconciliation Review. Institute for Healthcare Improvement Web site. Available at: /Tools/Medication+Reconciliation+Review.htm. Accessed August 29, 2005.

6. Caplan GA, Williams AJ, Daly B, Abraham K. A randomized, controlled trial of comprehensive geriatric assessment and multidisciplinary intervention after discharge of elderly from the emergency department—the DEED II study. J Am Geriatr Soc. 2004;52:1417-1423. [ go to PubMed ]

7. Smith JD, Coleman EA, Min SJ. A new tool for identifying discrepancies in postacute medications for community-dwelling older adults. Am J Geriatr Pharmacother. 2004;2:141-147. [ go to PubMed ]

8. Hanlon JT, Lindblad CI, Gray SL. Can clinical pharmacy services have a positive impact on drug-related problems and health outcomes in community-based adults? Am J Geriatr Pharmacother. 2004;2:3-13. [ go to PubMed ]

9. Strom BL, Hennessy S. Pharmacist care and clinical outcomes for patients with reactive airways disease. JAMA. 2002;288:1642-1643. [ go to PubMed ]

10. How to Take Your Medications Safely. Institute for Safe Medication Practices Web site. Available at: Accessed August 22, 2005.

11. Request a Brown-Bag Check-up. ISMP Medication Safety Alert! Institute for Safe Medication Practices Web site. Available at: Accessed August 22, 2005.


Table. Examples of Adverse Events after Discharge from Hospital (3)


  • Severe candidal esophagitis, presenting as food-bolus blockage, in a patient treated with corticosteroids.
  • Antibiotic-associated diarrhea, leading to dehydration and syncope, in a patient treated for pneumonia. The patient was readmitted to hospital and given fluids intravenously; the antibiotic therapy was stopped.


  • Profound hypoglycemia necessitating readmission, which developed days after discharge in a patient treated orally with hypoglycemics.
  • Acute exacerbation of congestive heart failure in a patient with severe left ventricular dysfunction for whom diltiazem was prescribed. The patient’s condition was inadequately monitored after discharge.
  • Profound hyperkalemia and acute renal failure in a patient treated with an angiotensin-converting-enzyme inhibitor and diuretics. The electrolyte levels were not monitored after discharge.

Not Preventable or Ameliorable

  • Self-limited antibiotic-associated nausea.

“Adverse events among medical patients after discharge from hospital.” Reprinted from CMAJ 03-Feb-04; 170(3), Page(s) 345-349 by permission of the publisher. © 2004 CMA Media Inc.


Figure. Medication Discrepancy Tool Produced by Care Transitions Program at University of Colorado at Denver and Health Sciences Center.

(Click thumbnail to view PDF)
This project was funded under contract number 75Q80119C00004 from the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services. The authors are solely responsible for this report’s contents, findings, and conclusions, which do not necessarily represent the views of AHRQ. Readers should not interpret any statement in this report as an official position of AHRQ or of the U.S. Department of Health and Human Services. None of the authors has any affiliation or financial involvement that conflicts with the material presented in this report. View AHRQ Disclaimers
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