Patient Safety Advisory Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 4 (Dec. 2005) Produced by ECRI & ISMP under contract to the Pennsylvania Patient Safety Authority The Beers Criteria: Screening for Potentially Inappropriate Medications in the Elderly P rescribing medications for elderly patients pre- sents many unique challenges. As we age, our bodies undergo physiologic changes that affect how may remain within normal limits because the elderly have less lean body mass and produce less creatinine. These “normal” serum creatinine levels medications are absorbed, distributed, metabolized, may mislead practitioners to believe that drug adjust- and eliminated. These changes often make elderly ments for renally excreted drugs are not necessary. patients more sensitive to the effects of medications. However, this is often not the case, as these physiol- However, there are criteria that can help practitioners ogic changes to the kidneys decrease renal clearance reduce the risk of patient harm by guiding more ap- of drugs necessitating a dose adjustment. propriate drug selection in the elderly commonly known as the Beers Criteria. Many drugs produce active metabolites in clinically significant concentrations. Examples include some Between 1960 and 1994, the number of persons benzodiazepines (e.g., diazepam, chlordiazepoxide), aged 65 and older doubled, and individuals aged 85 tertiary amine antidepressants (e.g., amitriptyline, years and older increased 274%.1 Today, people over imipramine), antipsychotics (e.g., chlorpromazine, age 65 account for 15% of the US population but con- thioridazine, risperidone), and opioid analgesics (e.g., sume more than one-third of all prescription and over- meperidine, propoxyphene). Age-related decreases in the-counter (OTC) medications.2,3 In Pennsylvania, renal clearance, particularly in patients with any addi- 41% of patients admitted to the hospital are 65 years tional renal disease, can lead to increased accumula- or older.4 It should therefore come as no surprise that tion of these metabolites, increasing the risk of toxicity patients over age 65 are involved in 41% of the ad- unless maintenance doses are reduced. verse drug reaction reports and almost 60% of the medication-related fall reports submitted to PA-PSRS. Adverse Drug Events and Beers Criteria Many studies demonstrate the vulnerability of elderly Pharmacodynamics in the Elderly5 patients to adverse drug events (ADEs) that may be As a person ages their total body water decreases due to the physiologic changes of aging. Problems in while their relative percentage of body fat increases. this population such as depression, constipation, falls, These changes affect how some drugs are distributed immobility, confusion, urinary retention, incontinence, in the body. The decrease in total body water can anorexia, and hip fractures have been linked to pre- lead to higher blood concentrations of some water- ventable ADEs. One study showed that 30% of hospi- soluble drugs. The relative increase in body fat may tal admissions of elderly patients may be linked to increase the total amount of drug stored in the body drug-related problems including toxic effects.6,7 A for lipid-soluble drugs and may result in longer half- 1997 study of ADEs found that 35% of ambulatory lives of those medications. Some drugs bind to albu- older adults experienced an ADE and 29% required min in the blood stream, but with age, serum albumin health care services (physician, emergency depart- levels decrease. This may enhance a drug’s effect by ment, or hospitalization) for the ADE.6 ADEs also af- increasing serum concentrations of unbound (active) fect drug regimen adherence in the elderly. A study of drug. 20 elderly patients hospitalized due to non-adherence Many medications are metabolized by the liver. With age, decreased hepatic mass and hepatic blood flow This article is reprinted from the PA-PSRS Patient Safety Advisory, Vol. 2, No. can slow the rate of hepatic elimination. In addition, 4—Dec. 2005. The Advisory is a publication of the Pennsylvania Patient Safety Authority, produced by ECRI & ISMP under contract to the Authority as hepatic clearance of many drugs, such as diazepam, part of the Pennsylvania Patient Safety Reporting System (PA-PSRS). amitriptyline, and chlordiazepoxide, carried out by the cytochrome P-450 system often diminishes with age. Copyright 2005 by the Patient Safety Authority. This publication may be re- Overall, the clearance of drugs metabolized by the printed and distributed without restriction, provided it is printed or distributed in its entirety and without alteration. Individual articles may be reprinted in their liver is typically decreased 30 to 40% in the elderly. entirety and without alteration provided the source is clearly attributed. Renal size and renal blood flow also decrease signifi- To see other articles or issues of the Advisory, visit our web site at cantly with age. However, serum creatinine levels www.psa.state.pa.us. Click on “Advisories” in the left-hand menu bar. ©2005 Pennsylvania Patient Safety Authority Page 1 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2 No. 4 (Dec. 2005) The Beers Criteria: Screening for Potentially Inappropriate Medications in the Elderly (Continued) found that adverse effects were the most common atrial arrhythmias. Diminished renal clear- reason (35%).8 Data from PA-PSRS show that 62% ance of this medication increases the risk of of medication-related falls that result in a Serious toxicity. Event affected the elderly. 3. Drug-disease interaction, i.e., medications to be In 1991, 13 nationally recognized experts in geriatrics avoided for patients with specific co-morbid con- reached a consensus on explicit criteria for certain ditions. Examples include: medications that may lead to ADEs and were consid- a) Patients with cognitive impairment receiving ered to be inappropriate for use in nursing home pa- medications such as barbiturates, anticho- tients. These criteria were originally developed by Dr. linergics and muscle relaxants, which can Mark Beers and are commonly referred to as the worsen cognitive performance. “Beers Criteria.” The criteria, most recently updated in b) Patients with a history of syncope or falls 2003,9,10 are based on the risk-benefit definition of receiving medications such as short or inter- appropriateness, meaning that the use of a medica- mediate-acting benzodiazepines and tricyclic tion is considered to be appropriate if its use has po- antidepressants (amitriptyline [ELAVIL], tential benefits that outweigh potential risks.11 doxepin [SINEQUAN], and imipramine [NORPRAMIN]) which may produce ataxia, The Beers criteria define three categories of drug use impair psychomotor function, and increase or selection that are inappropriate for elderly patients. falls. The categories, along with some examples are: The Beers criteria are intended for persons older than 1. Inappropriate drug choice, i.e., medications gen- 65 years of age, regardless of their level of frailty. The erally to be avoided in the elderly population. criteria also provide a rating of severity for adverse Examples include: outcomes (severe vs. less severe) as well as a sum- a) Long-acting benzodiazepines, including di- mary of the prescribing concerns associated with the azepam (VALIUM), flurazepam (DALMANE), medication. An abbreviated list of these medications and chlordiazepoxide (LIBRIUM) which have can be found in Table 1. A complete list is available at long half-lives. This can lead to accumula- http://mqa.dhs.state.tx.us/qmweb/MedSim/ tion of the drug, leading to excessive seda- MedSimTable1.htm. tion and an increase in the risk of falls and fractures. Today, the Beers criteria are the most widely used b) Meperidine (DEMEROL), which can cause criteria for identifying drugs that potentially increase confusion and its metabolites can lead to the likelihood of ADEs in elderly patients.12 The crite- seizures. ria were adopted by the Centers for Medicare & Medi- c) Anticholinergics and antihistamines, includ- caid Services (CMS) in July 1999 for evaluation of ing diphenhydramine (BENADRYL), chlor- medication therapy in nursing home patients. pheniramine (CHLORTRIMETON), hy- droxyzine (ATARAX, VISTARIL) and pro- Numerous studies confirm that contraindicated medi- methazine (PHENERGAN). These agents cation use remains a serious problem for the elderly have potent anticholinergic effects and in a variety of healthcare settings.13-15 However, until cause confusion and sedation. Diphenhy- recently, there was no published evidence demon- dramine may be used in the lowest effective strating that the medications listed on the Beers crite- dose and only for emergency treatment of ria were actually associated with adverse outcomes. allergic reactions. In Spring 2005, a study of the association between potentially contraindicated prescribing and hospitali- 2. Excess dosage, i.e., medications at a dose or zation and death among elderly nursing home resi- duration of therapy not to be exceeded. Exam- dents showed that:16 ples include: a) Long-term use of stimulant laxatives such as a) The risk of hospitalization was almost 30% bisacodyl (DULCOLAX) and cascara higher among residents who, in the preceding sagrada, which may be appropriate in the month, received potentially contraindicated presence of opiate analgesic use, but may medications that appear on the Beers criteria, exacerbate bowel dysfunction. and 33% higher among residents who received b) Doses for digoxin (LANOXIN) should not these medications for two consecutive months, exceed 0.125 mg/day except when treating compared with residents with no exposure. Page 2 ©2005 Pennsylvania Patient Safety Authority Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 4 (Dec. 2005) The Beers Criteria: Screening for Potentially Inappropriate Medications in the Elderly (Continued) Table 1. Abbreviated Beers List of Medications with Increased Risk of Adverse Drug Events in Patients Over 65 Medications Reason that Use is a Problem Pain Relievers propoxyphene and combination products Used to control pain. Propoxyphene offers little pain-relieving advantage over acetaminophen (Tylenol®), yet (Darvon®, Darvocet N-100®) has the side effects of other narcotics. Meperidine (Demerol®) Used to treat pain. Meperidine is not an effective oral pain reliever and has many disadvantages compared to other narcotics. Avoid using in older persons. Antidepressants amitriptyline (Elavil®) Used to treat depression. These medications can cause sedation, weakness, blood pressure changes, dry doxepin (Sinequan®) mouth, problems with urination, and can lead to falls and fractures. Sleeping Pills and Antianxiety Medications flurazepam (Dalmane®) Used to treat insomnia. This medication produces prolonged sedation/sleepiness (often lasting for days and can worsen if taken daily) and can increase the risk of falls and fractures. alprazolam (Xanax®) 2 mg Used to treat insomnia and anxiety. Older people should be prescribed small doses of these medications. Total lorazepam (Ativan®) 3 mg daily doses should rarely exceed the suggested maximum doses noted to the left. oxazepam (Serax ®) 60 mg temazepam (Restoril®) 15 mg triazolam (Halcion®) 0.25mg zolpidem (Ambien®) 5 mg chlordiazepoxide (Librium®) Used to treat insomnia and anxiety. Chlordiazepoxide and diazepam produce prolonged sedation (often lasting diazepam (Valium®) several days and can worsen if taken daily) and can increase the risk of falls and fractures. Heart Medications digoxin (Lanoxin®) [doses above 0.125 mg] Used to treat abnormal heart rhythms and heart failure. Because of decreased processing of digoxin by the kidney, doses in older persons should rarely exceed 0.125 mg daily, except when treating certain types of abnormal heart rhythms. dipyridamole (Persantine®) Used to help stop blood from clotting in people who have experienced strokes, heart attacks, and other condi- tions. Dipyridamole frequently causes light-headedness upon standing in older persons. Dipyridamole has been proven beneficial only in patients with artificial heart valves. Whenever possible, its use in older persons should be avoided. methyldopa (Aldomet®) Used to treat high blood pressure. Methyldopa may cause a slowed heart beat and worsen depression. Alter- methyldopa/HCTZ (Aldoril®) nate treatments for hypertension are generally preferred. Diabetes Medications chlorpropamide (Diabinese®) Used to control blood sugar in people with diabetes. Chlorpropamide can cause prolonged and serious low blood sugar. Stomach and Intestinal Medications dicyclomine (Bentyl®) Used to treat stomach and intestinal cramps. These medications can cause sedation, weakness, blood pres- hyoscyamine (Levsin®, Levsinex®) sure changes, dry mouth, problems with urination, and can lead to falls and fractures. All of these drugs are propantheline (Pro-Banthine®) best avoided in older persons, especially for long term use. belladonna alkaloids (Donnatal®) trimethobenzamide (Tigan®) Used to control nausea. This is one of the least effective medications used to control nausea and vomiting, yet can cause severe side effects, such as stiffness, shuffling gate, difficulty swallowing, and tremor. Antihistamines chlorpheniramine (Chlor-Trimeton®) Used to treat the runny nose of the common cold and allergy symptoms. Most nonprescription and many diphenhydramine (Benadryl®) prescription antihistamines can cause sedation, weakness, blood pressure changes, dry mouth, problems with hydroxyzine (Vistaril®, Atarax®) urination, and can lead to falls and fractures. Many cough and cold preparations are available without antihista- mines, and these are safer substitutes in older persons. cyproheptadine (Periactin®) promethazine (Phenergan®) diphenhydramine (Benadryl®) Used to treat allergies and insomnia. Diphenhydramine can cause sedation, weakness, blood pressure changes, dry mouth, problems with urination, and can lead to falls and fractures.. When used to treat or pre- vent allergic reactions, it should be used in the smallest possible dose and with great caution. Adapted from: http://www.seniorcarepharmacist.com/inappropriate/. Used with permission. For a complete list, go to http://mqa.dhs.state.tx.us/qmweb/MedSim/MedSimTable1.htm ©2005 Pennsylvania Patient Safety Authority Page 3 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2 No. 4 (Dec. 2005) The Beers Criteria: Screening for Potentially Inappropriate Medications in the Elderly (Continued) b) The odds of death in any month were 21% • Placing alerts into pharmacy order entry systems higher among residents who had exposure to and computerized prescriber order entry sys- these medications during the month of death or tems for those medications on the Beers list that the preceding month, compared to those with no are prescribed for patients over age 65. exposure. • Increasing practitioner awareness of the Beers A second study published this year showed a positive criteria through educational sessions and distrib- association between adverse drug reactions (ADRs) uting laminated lists of the Beers criteria. and drug prescribing practices that are contrary to the • Monitoring elderly patients for ADRs and poten- Beers criteria.12 Patients who experienced ADRs re- tial ADEs who are receiving medications that ceived a greater number of potentially inappropriate appear on the Beers criteria. medications. In addition, there was a positive correla- tion between the number of ADRs and the number of • Identifying medications in your reports to PA- prescribed drugs. The study also found a positive as- PSRS for those patients involved in falls to help sociation between potentially inappropriate drug pre- identify those medications that are most prob- scribing, as defined by the Beers criteria and ADRs, lematic to this population. some of which were preventable, among elderly out- • Analyzing reports of ADRs, falls, and medication patients. errors in your organization’s PA-PSRS reports for patients over age 65 to see if they were re- Analysis of PA-PSRS data shows that many reports ceiving medications that may not follow the of ADRs and falls involving the elderly cite a medica- Beers criteria. tion that appears on the Beers criteria, such as meperidine (DEMEROL), temazepam (RESTORIL), • When it is medically necessary to prescribe a promethazine (PHENERGAN), and diphenhydramine drug to an elderly patient that is on the Beers (BENADRYL). Twenty percent (20%) of those ADR criteria, consider starting at the lowest possible reports in patients over 65 describe patients receiving dose. For example, medications like PHENER- PHENERGAN (promethazine) and developing mental GAN (promethazine) could be prescribed at status changes such as agitation, “jitters,” and rest- doses as low as 6.25 mg, which may reduce the lessness. Also, 58% of all medication-related falls in likelihood of an ADE. the elderly involve medications categorized as benzo- diazepines or opiates, some of which may be contra- By paying special attention to elderly patients who are indicated according to the Beers criteria. receiving medications that appear on the Beers list we may be able to prevent ADEs and ADRs in this Conclusion vulnerable population. The use of medications in the elderly population pre- sents many challenges for all healthcare practitioners. Notes Due to metabolic changes, the elderly are more prone 1. Hobbs FB. The Elderly Population [online]. U.S. Census Bureau, to ADEs as well as ADRs. Though Beers’ 1991 crite- Population Division and Housing and Household Economic Statis- tics Division. 18 Jan 2001. [Cited 18 Aug 2005.] Available from ria were developed for elderly nursing home residents Internet: http://www.census.gov/population/www/pop-profile/ and the 1997 criteria for community-dwelling elderly, elderpop.html. these criteria can also be used in the acute care set- 2. Querna E. Drugs for seniors: elderly patients should double- ting. The latest studies suggest that many ADRs we check their prescriptions [online]. USNews.com. 2 Nov 2004. [Cited 18 Aug 2005.] Available from Internet: http://www.usnews.com/ attribute to medications in the elderly may actually be usnews/health/briefs/seniorshealth/hb041102a.htm. due to preventable ADEs. If the Beers criteria were 3. US Food and Drug Administration. Medications and Older Peo- followed, these ADRs may not have occurred. ple [online]. Sep 2003. [Cited 18 Aug 2005.] Available from Inter- net: http://www.fda.gov/fdac/features/1997/697_old.html. 4. Pennsylvania Health Care Cost Containment Council. County The following practices may help to prevent ADEs profile results, statewide report, utilization by age and sex [online]. and ADRs among the elderly: 2004. [cited 19 Aug 2005.] Available from Internet: http:// www.phc4submit.org/countyprofiles/CountyProfileResults.aspx? • Reviewing the medication profile upon admis- CNTYFIPS=% sion and discharge against the Beers criteria. &CNTYNAME=Statewide&Begin=20041&End=20044 5. Clinical Pharmacology. In: Beers MH, ed. The Merck Manual of Consider substituting non-drug based treat- Geriatrics, 3rd Edition [online]. Whitehouse Station (NJ): Merck ments. For example, studies have shown that Research Laboratories; 2000. [Cited 18 Aug 2005.] http:// non-pharmacologic sleep protocols for inpatients www.merck.com/mrkshared/mmg/sec1/ch6/ch6b.jsp are an effective means of reducing the use of sedatives and the risks of ADEs.17 Page 4 ©2005 Pennsylvania Patient Safety Authority Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 4 (Dec. 2005) The Beers Criteria: Screening for Potentially Inappropriate Medications in the Elderly (Continued) 6. Hanlon JT, Schmader KE, Kornkowski MJ, et al. Adverse drug 13. Chin MH, Wang LC, Jin L, et al. Appropriateness of medication events in high risk older outpatients. J Am Geriatr Soc selection for older persons in an urban academic emergency de- 1997;45:945-8. partment. Acad Emerg Med 1999; 6:1232-42. 7. Bootman JL, Harrison DL, Cox E. The health care cost of drug- 14. Aparasu RR, Fliginger SE. Inappropriate medication prescribing related morbidity and mortality in nursing facilities. Arch Intern Med for the elderly by office-based physicians. Ann Pharmacother 1997;157:2089-96. 1997;31:823-9. 8. Col N, Fanale JE, Kronholm P. The role of medication noncom- 15. Schmader KE, Hanlon JT, Landsman PB, Samsa GP, Lewis IK, pliance and adverse drug reactions in hospitalizations of the eld- Weinberger M. Inappropriate prescribing and health outcomes in erly. Arch Intern Med 1990;150:841-5. elderly veteran outpatients. Ann Pharmacother 1997;31:529-33 9. Beers MH. Explicit criteria for determining potentially inappropri- 16. Lau et al. Hospitalization and Death Associated With Potentially ate medication use by the elderly. Arch Intern Med 1997;157:1531- Inappropriate Medication Prescriptions Among Elderly Nursing 6. Home Residents. Arch Intern Med 2005;165:68-74. 10. Fick DM, Cooper, JW,Wade WE, et al. Updating the Beers 17. McDowell JA, Mion LC, Lydon TJ, Inouye SK: A nonpharma- Criteria for Potentially Inappropriate Medication Use in Older cologic sleep protocol for hospitalized older patients. Adults. Arch Intern Med 163:2716-24. December 2003. J.Am.Geriatr.Soc 1998; 46: 700-5. 11. Beers MH, Ouslander JG, Rollingher J, Reuben DB, Beck JC. Explicit criteria for determining inappropriate medication use in nursing home residents. Arch Intern Med 1991;151:1825-32 12. Chang, CM. et al. Use of the Beers Criteria to Predict Adverse Drug Reactions among First-Visit Elderly Outpatients. Pharmaco- therapy 2005;25(6):831-8 ©2005 Pennsylvania Patient Safety Authority Page 5 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2 No. 4 (Dec. 2005) An Independent Agency of the Commonwealth of Pennsylvania The Patient Safety Authority is an independent state agency created by Act 13 of 2002, the Medical Care Availability and Reduction of Error (“Mcare”) Act. Consistent with Act 13, ECRI, as contractor for the PA-PSRS program, is issuing this newsletter to advise medical facilities of immediate changes that can be instituted to reduce serious events and incidents. For more information about the PA- PSRS program or the Patient Safety Authority, see the Authority’s website at www.psa.state.pa.us. ECRI is an independent, nonprofit health services research agency dedicated to improving the safety, efficacy and cost-effectiveness of healthcare. ECRI’s focus is healthcare technology, healthcare risk and quality management and healthcare environmental management. ECRI provides information services and technical assistance to more than 5,000 hospitals, healthcare organizations, ministries of health, government and planning agencies, and other organizations worldwide. The Institute for Safe Medication Practices (ISMP) is an independent, nonprofit organization dedicated solely to medication error prevention and safe medication use. ISMP provides recommendations for the safe use of medications to the healthcare community including healthcare professionals, government agencies, accrediting organizations, and consumers. ISMP's efforts are built on a non-punitive approach and systems-based solutions. Page 6 ©2005 Pennsylvania Patient Safety Authority