Focus on Adverse Drug Events
Important Medication Safety Definitions
ADRs are harm directly caused by a drug at normal doses during normal use.1
Medication errors may occur during prescribing, transcribing, dispensing, adherence, or monitoring of drug therapy, and may or may not result in harm. In all cases ADRs are ADEs; however an ADE that results from a medication dosing error does not become an ADR if the patient suffers no harmful effects.1
An allergy is defined by the US Department of Veterans Affairs as an ADR mediated by an immune response such as a rash or hives. A side effect is defined as "an expected and known effect of a drug that is not the intended therapeutic outcome." The term "side effect" tends to normalize the concept of drug-related injury; it has been recommended that this term should be avoided in favor of ADR.1
Major Public Health Concern
The potential for ADEs is common regardless of setting. ADEs result in more than 700,000 emergency department visits each year, with nearly 120,000 patients hospitalized for further treatment after emergency visits for ADEs. Older adults, aged 65 and older, are twice as likely as others to visit emergency departments for ADEs and are nearly seven times more likely to be hospitalized following an emergency department visit.4 One in six hospital admissions of older adults occurs because of ADEs, a rate four times that of younger people. Hospital admissions because of ADEs increase to one in three for individuals aged 75 and older. While hospitalized, one in six older patients experiences at least one ADE. In community settings, one in five older adults is taking potentially inappropriate medications.5
Long term care (LTC) residents are at a particularly high risk for ADEs; the average LTC resident uses seven to eight different medications each month, with about one-third of residents receiving nine or more medications.6 In LTC centers, an estimated 2 million ADEs occur each year with at least 10 ADEs occurring each month in an average size center. One in seven LTC residents will be hospitalized as a result of an ADE.7
In an effort to increase recognition and prevention of ADEs in skilled nursing facilities, the Centers for Medicare & Medicaid Services (CMS) is piloting "Medication Adverse Drug Event" focus surveys. CMS noted that a review by the Office of Inspector General found that one in three skilled nursing facility (SNF) residents was harmed by an adverse event or temporary harm event within the first 35 days of an SNF stay and 37% of the adverse events were related to medication. The second most frequent cause of medication-related adverse events was excessive bleeding related to anticoagulant use, causing harm ranging from hospitalization to death.8
ADEs Are Often Preventable
Strategies to Prevent ADE Risk
• Implement a team approach. Medication optimization is most effective when there is a cooperative relationship among the physician, nurses, nurse aides, pharmacist, other health care professionals, patient, and family. A team approach promotes optimal use of medications, reduces ADEs, and promotes cost-effective drug prescribing practices. This collaboration provides better insight around the patient's needs, typical behaviors, and responses, while also increasing the number of people who can observe a patient before and after a medication is started.
• Increase awareness of high-risk medications. ADEs can occur with any medication, including over-the-counter medications and herbal remedies, making it difficult to predict which medication will result in an ADE for an individual patient. However, in general we know that certain risk factors such as increasing age, polypharmacy, comorbid conditions, and certain medication classes have been identified as consistently causing potential ADEs, which makes closely monitoring them a priority (see Table 1).
High-risk medications include anticoagulants, diabetes agents (insulin and oral agents), narcotics (opioids), anti-infectives, antineoplastics, sedatives (benzodiazepines), and antipsychotics.
Those medications requiring laboratory monitoring due to narrow therapeutic windows as with anticoagulants such as warfarin, diabetic medications, and seizure medications (phenytoin) and digoxin are commonly implicated as creating a high risk for potential ADEs.
The CMS drug utilization review criteria target eight prescription drug classes: digoxin, calcium channel blockers, angiotensin-converting enzyme inhibitors, H-2 receptor antagonists, NSAIDs, benzodiazepines, antipsychotics, and antidepressants, and focus on four types of prescribing problems: inappropriate dosage, inappropriate duration of therapy, duplication of therapies, and potential for drug-drug interactions. NSAIDs and benzodiazepines were the implicated the drug classes with the most potential problems among older adults in the community.10
A systematic review of nine international studies attributed most preventable medication-related admissions to antithrombotic medications, diuretics, and NSAIDs.11 In another study, two-thirds of all medication-related admissions to the hospital involved antithrombotic and antidiabetic medications, almost always by unintentional overdose.12 In a prospective study of 1,225 hospital admissions related to ADEs, 20 of 28 deaths were due to gastrointestinal or intracranial bleeding and five were due to renal failure.13
In LTC, preventable ADEs have been most frequently associated with atypical antipsychotics and warfarin therapy. In a 12-month observational study of 25 SNFs with 490 LTC residents taking warfarin, 720 ADEs were noted, with 625 of the events considered minor, 82 serious, and 13 life threatening; 57% of the serious events were considered preventable.14
ADEs Occur at All Phases of the Medication Utilization Process
Recognize Signs and Symptoms of Possible ADEs
Confusion, oversedation, delirium, and hemorrhagic and gastrointestinal events have been noted as the most common ADEs in a number of studies involving LTC facilities.
Orthostatic hypotension as well as falls and associated skeletal fractures increase with age and are attributed to multiple causes, including medication side effects, polypharmacy, and comorbid medical conditions.
Failure to recognize evidence-based guidelines that suggest avoiding excessive blood pressure lowering (eg, goal blood pressure guidelines of < 140/90 mmHg for older adults) increases the risk of falls and other ADEs. The use of psychoactive medications including antipsychotics, antidepressants, benzodiazepines, and sedative/hypnotics in older adults should be limited to reduce the risk of falls.
Communicating medication order changes between health care team members including the patient, family, and nursing assistants is critical because many ADEs occur near the onset of a new medication or dosage change. With this information, all team members will be in a better position to monitor for and report changes in a patient's condition with an increased urgency around evaluating medications as a potential cause.
Reduce the Number of Prescribers
Decrease the Number of Medications
Additionally, new medications should be prescribed sparingly to help limit the number of an older adult's medications because each new medication adds more than one ADE each year, and taking six or more medications increases this risk fourfold.
Another consideration to reduce the number of medications being used by an older adult is to avoid treating side effects of one medication with another medication; for example, starting an antihistamine for opioid-induced pruritus even when the symptoms are likely associated with the initiation of a new medication. Instead, the drug causing the side effect may be replaced with a different therapy.
Involve Patients/Family in Shared Decision-Making
Improve Appropriate Prescribing
Utilize STOPP (screening tool of older adults' potentially inappropriate prescriptions) criteria: STOPP criteria identify five medication classes: proton-pump inhibitors, long-acting benzodiazepines, NSAIDs, nonselective beta blockers, and tricyclic antidepressants. These five categories of medications account for nearly 80% of the inappropriate prescribing detected by the STOPP criteria in the outpatient setting. Additionally, utilize START (screening tool to alert to right treatment) criteria, such as an ACE inhibitor in a patient with congestive heart failure.5
Reducing Patient Risks
— Mark D. Coggins, PharmD, CGP, FASCP, is senior director of pharmacy services for skilled nursing centers operated by Diversicare in eight states, and is a director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.
2. Zubenko GS, Sunderland T. Geriatric psychopharmacology: why does age matter? Harv Rev Psychiatry. 2000;7(6):311-333.
3. Jacobson SA, Pies RW, Katz IR. Clinical Manual of Geriatric Psychopharmacology. Washington, D.C.: American Psychiatric Publishing; 2007.
4. Medication safety program: adults and older adult adverse drug events. Centers for Disease Control and Prevention website. http://www.cdc.gov/MedicationSafety/Adult_AdverseDrugEvents.html. Updated October 2, 2012. Accessed September 28, 2015.
5. Pretorius RW, Gataric G, Swedlund SK, Miller JR. Reducing the risk of adverse drug events in older adults. Am Fam Physician. 2013;87(5):331-336.
6. Doshi JA, Shaffer T, Briesacher BA. National estimates of medication use in nursing homes: findings from the 1997 Medicare current beneficiary survey and the 1996 medical expenditure survey. J Am Geriatr Soc. 2005;53(3):438-443.
7. Handler SM, Hanlon JT. Detecting adverse drug events using a nursing home specific trigger tool. Ann Longterm Care. 2010;18(5):17-22.
8. Adverse events in nursing homes. Centers for Medicare & Medicaid Services website. https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/QAPI/Adverse-Events-NHs.html. Updated September 22, 2015.
9. Beijer HJ, de Blaey CJ. Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm World Sci. 2002;24(2):46-54.
10. Hanlon JT, Schmader KE, Boult C, et al. Use of inappropriate prescription drugs by older people. J Am Geriatr Soc. 2002;50(1):26-34.
11. Howard RL, Avery AJ, Slavenburg S, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2006;63(2):136-147.
12. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012.
13. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329(7456):15-19.
14. Gurwitz JH, Field TS, Radford MJ, et al. The safety of warfarin therapy in the nursing home setting. Am J Med. 2007;120(6):539-544.
15. Green JL, Hawley JN, Rask KJ. Is the number of prescribing physicians an independent risk factor for adverse drug events in an elderly outpatient population? Am J Geriatr Pharmacother. 2007;5(1):31-39.