Topic Resources
Medication-related problems are common in older adults and include drug ineffectiveness, adverse drug effects, overdosage, underdosage, inappropriate treatment, inadequate monitoring, nonadherence, and drug-drug or drug-disease interactions. (See also Overview of Pharmacologic Therapy in Older Adults.)
Medications may be ineffective in older adults because clinicians under-dose or do not titrate the dose over time (eg, because of increased concern about adverse effects) or because adherence is poor (eg, because of financial or cognitive limitations).
Adverse drug effects are effects that are unwanted, uncomfortable, or dangerous. Common examples are oversedation, confusion, hallucinations, falls, diarrhea, constipation, and bleeding. Among ambulatory people ≥ 65, adverse drug effects occur at a rate of about 50 events per 1000 person-years (1). Hospitalization rates due to adverse drug effects are 4 to 7 times higher in older patients than in younger patients; these hospitalizations in older patients are most commonly due to anticoagulants, antibiotics, diabetes agents, opioid analgesics, and antipsychotics (2, 3).
References
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(9):1107-1116. doi:10.1001/jama.289.9.1107
2. Salvi F, Marchetti A, D'Angelo F, Boemi M, Lattanzio F, Cherubini A. Adverse drug events as a cause of hospitalization in older adults. Drug Saf. 2012;35 Suppl 1:29-45. doi:10.1007/BF03319101
3. Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014. JAMA. 2016;316(20):2115-2125. doi:10.1001/jama.2016.16201
Reasons for Medication-Related Problems
Adverse drug effects can occur in any patient, but certain characteristics of older adults make them more susceptible. For example, older adults often take multiple medications and have age-related changes in pharmacodynamics and pharmacokinetics; both increase the risk of adverse effects.
At any age, adverse drug effects may occur when medications are prescribed and taken appropriately; eg, new-onset allergic reactions are not predictable or preventable. However, adverse effects are thought to be preventable in many cases in older adults (1).
In older adults, a number of common causes for adverse drug effects, ineffectiveness, or both are preventable. Such preventable causes include:
Untreated medical condition
Inadequate communication with patients or between health care professionals (particularly during health care transitions) is a major cause of adverse drug effects in older adults. Many medication-related problems could be prevented if greater attention were given to medication reconciliation when patients are admitted or discharged from the hospital or at other care transitions (transfer from nursing home to hospital, or skilled nursing facility to home) (2-4). Another source of adverse drug effects is the lack of ongoing evaluation of drug effectiveness and the continued need for specific medications.
Drug-disease interactions
A medication given to treat one disease can exacerbate another disease regardless of patient age, but such interactions are of special concern in older adults. Distinguishing often subtle adverse drug effects from the effects of disease is difficult and may lead to a prescribing cascade. The American Geriatrics Society Beers Criteria® is commonly used to identify potential drug-disease interactions in older adults and provides medical management recommendations (5).
A prescribing cascade occurs when the adverse effect of a medication is misinterpreted as a symptom or sign of a new disorder and a new medication is prescribed to treat it. The new, unnecessary medication may cause additional adverse effects, which may then be misinterpreted as yet another disorder and treated unnecessarily, and so on.
Many medications have adverse effects that resemble symptoms of disorders common in older adults or changes due to aging. The following are examples:
Antipsychotics may cause symptoms that resemble Parkinson disease. In older adults, these symptoms may be diagnosed as Parkinson disease and treated with dopaminergic drugs, possibly leading to adverse effects from the antiparkinson drugs (eg, orthostatic hypotension, delirium, hallucinations, nausea).
Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) may be prescribed for patients with dementia. These medications may cause diarrhea or urinary frequency or urge incontinence. Patients may then be prescribed an anticholinergic drug (eg, oxybutynin) to treat the new symptoms. Thus, an unnecessary medication is added, increasing the risk of adverse drug effects and drug-drug interactions. A better strategy is to reduce the dose of the cholinesterase inhibitor or consider a different treatment for dementia (eg, memantine) with a different mechanism of action.(eg, donepezil, rivastigmine, galantamine) may be prescribed for patients with dementia. These medications may cause diarrhea or urinary frequency or urge incontinence. Patients may then be prescribed an anticholinergic drug (eg, oxybutynin) to treat the new symptoms. Thus, an unnecessary medication is added, increasing the risk of adverse drug effects and drug-drug interactions. A better strategy is to reduce the dose of the cholinesterase inhibitor or consider a different treatment for dementia (eg, memantine) with a different mechanism of action.
Calcium channel blockers (eg, amlodipine, nifedipine, felodipine) may be prescribed for patients with hypertension. These medications may treat the hypertension appropriately, but they may also cause peripheral edema. Patients may then be prescribed diuretic therapy (eg, furosemide), which may then cause hypokalemia necessitating potassium supplementation. A better strategy is to reduce the dose or discontinue the calcium channel blocker in favor of other antihypertensive drugs, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers. (eg, amlodipine, nifedipine, felodipine) may be prescribed for patients with hypertension. These medications may treat the hypertension appropriately, but they may also cause peripheral edema. Patients may then be prescribed diuretic therapy (eg, furosemide), which may then cause hypokalemia necessitating potassium supplementation. A better strategy is to reduce the dose or discontinue the calcium channel blocker in favor of other antihypertensive drugs, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
In older patients, prescribers should always consider the possibility that a new symptom or sign is due to existing pharmacologic therapy.
Drug-drug interactions
Because older adults often take many medications, they are particularly vulnerable to drug-drug interactions. Older adults also frequently use medicinal herbs and other dietary supplements and may not share this with health care professionals. Medicinal herbs can interact with prescribed drugs and lead to adverse effects. For example, ginkgo biloba extract taken with warfarin can increase risk of bleeding, and St. John's wort taken with a selective serotonin reuptake inhibitor (SSRI) can increase risk of serotonin syndrome. Therefore, clinicians should ask patients specifically about dietary supplement use, including medicinal herbs and vitamin supplements.and may not share this with health care professionals. Medicinal herbs can interact with prescribed drugs and lead to adverse effects. For example, ginkgo biloba extract taken with warfarin can increase risk of bleeding, and St. John's wort taken with a selective serotonin reuptake inhibitor (SSRI) can increase risk of serotonin syndrome. Therefore, clinicians should ask patients specifically about dietary supplement use, including medicinal herbs and vitamin supplements.
Drug-drug interactions in older adults are similar to those in the general population. However, induction of cytochrome P-450 (CYP450) drug metabolism by certain medications (eg, phenytoin, carbamazepine, rifampin) may be decreased in older adults; therefore, the change (increase) in drug metabolism may be less pronounced in older adults. Many other medications inhibit CYP450 metabolism and thus increase the risk of toxicity of medications that depend on that pathway for elimination. Because older adults typically use a larger number of drugs, they are at greater risk of multiple, difficult-to-predict CYP450 interactions. Multiple medication use can also make many drug interactions difficult to predict. For example, even if there is a known interaction between 2 drugs, that interaction may be different if a third or fourth drug is concurrently being administered. Also, concurrent use of ≥ 1 drug with similar adverse effects can increase risk or severity of adverse effects. by certain medications (eg, phenytoin, carbamazepine, rifampin) may be decreased in older adults; therefore, the change (increase) in drug metabolism may be less pronounced in older adults. Many other medications inhibit CYP450 metabolism and thus increase the risk of toxicity of medications that depend on that pathway for elimination. Because older adults typically use a larger number of drugs, they are at greater risk of multiple, difficult-to-predict CYP450 interactions. Multiple medication use can also make many drug interactions difficult to predict. For example, even if there is a known interaction between 2 drugs, that interaction may be different if a third or fourth drug is concurrently being administered. Also, concurrent use of ≥ 1 drug with similar adverse effects can increase risk or severity of adverse effects.
Inadequate monitoring
Monitoring medication use involves:
Documenting the indication for a new medication
Keeping a current list of medications used by the patient in medical records
Monitoring for achievement of therapeutic goals and other responses to new drugs
Monitoring necessary laboratory or other tests for efficacy or adverse effects (eg, sodium, potassium, magnesium, vitamin B12, heart rate, corrected QT interval [QTc])
Periodically reviewing drugs for effectiveness and continued need
Such measures are especially important for older patients. Lack of close monitoring, especially after new medications are prescribed, increases risk of polypharmacy, adverse effects and ineffectiveness.
Inappropriate medication selection
A medication is inappropriate if its potential for harm is greater than its potential for benefit. Inappropriate use of a medication may involve:
Choice of an unsuitable medication, dose, frequency of dosing, or duration of therapy
Duplication of therapy
Failure to consider drug interactions and appropriate indications for a drug
Appropriate medications that are mistakenly continued once an acute condition resolves (as may happen when patients move from one health care setting to another and the indication is not reevaluated)
Some classes of medications are of special concern in older adults. Some medications should be avoided altogether in older adults, some should be avoided only in certain situations, and others can be used but with close monitoring. The American Geriatrics Society Beers Criteria® lists potentially inappropriate medications for older adults by drug class; other similar lists are available (5). A list of some pharmacologic and nonpharmacologic alternatives with supporting references is also available (6). Clinicians must weigh potential benefits and risks of therapy in each patient. The criteria do not apply to patients at the end-of-life, when pharmacologic therapy decisions are much different.
Despite dissemination and knowledge of the American Geriatrics Society Beers Criteria® and other criteria, inappropriate medications are still being prescribed for older adults; about 45% of community-dwelling older adults receive at least one inappropriate medication (7). In such patients, risk of adverse effects is increased. In nursing home patients, inappropriate use also increases risk of hospitalization and death. In one study of hospitalized patients, 27.5% received a potentially inappropriate medication based on the American Geriatrics Society Beers Criteria® (8).
Some inappropriate medications (eg, diphenhydramine and oral nonsteroidal anti-inflammatory drugs [NSAIDs]) are available over-the-counter (OTC); thus, clinicians should specifically question patients about use of OTC drugs and discuss with patients the potential problems such agents can cause.Some inappropriate medications (eg, diphenhydramine and oral nonsteroidal anti-inflammatory drugs [NSAIDs]) are available over-the-counter (OTC); thus, clinicians should specifically question patients about use of OTC drugs and discuss with patients the potential problems such agents can cause.
Older adults are often prescribed medications (typically, analgesics, proton pump inhibitors, or hypnotics) for minor symptoms (including for adverse effects of other medications) that may be better treated with nonpharmacologic interventions (eg, exercise, physical therapy, massage, dietary changes, cognitive-behavioral therapy) or by lowering the dose of the medication causing adverse effects. Initiating additional medications is often inappropriate; benefit may be low, costs are increased, and the new medication may lead to additional toxicity.
Effectively eliminating inappropriate medication use in older adults requires more than avoiding a short list of medications and noting medication categories of concern. A patient’s entire medication regimen should also be assessed regularly to determine the continued need for a medication and weigh potential benefits against risks.
Lack of patient adherence
Drug effectiveness is often compromised by lack of patient adherence among ambulatory older adults. Adherence is affected by many factors, including language barriers, but not by age per se. Up to half of older adults do not take medications as directed, usually taking less than prescribed (underadherence). Causes are similar to those for younger adults. In addition, the following contribute:
Financial and physical constraints, which may make purchasing medications difficult
Cognitive problems or low health literacy, which may make taking medications as instructed difficult
Use of multiple medications (polypharmacy)
Use of medications that must be taken several times a day or in a specific manner
Lack of understanding about the intended benefits of a medication,the potential adverse effects, or the use of unconventional dosage forms, such as transdermal patches or inhalers
A regimen using too frequent or too infrequent dosing, multiple medications, or both may be too complicated for patients to follow. Clinicians should assess patients’ health literacy and abilities to adhere to a therapeutic regimen (eg, dexterity, hand strength, cognition, vision) and try to accommodate their limitations—eg, by arranging for or recommending easy-access containers, drug labels and instructions in large type, containers equipped with reminder alarms, containers filled based on daily drug needs, reminder telephone calls, or medication assistance. Pharmacists and nurses can help by providing education and reviewing prescription instructions with older adults at each encounter. Pharmacists may be able to identify a problem by noting whether patients obtain refills on schedule or whether a prescription seems illogical or incorrect. Many pharmacies and health systems can monitor refill patterns and contact patients and/or prescribers if prescriptions are not being refilled at appropriate intervals.
Overdosage
An excessive dose of an appropriate medication may be prescribed for older adults if the prescriber does not consider age-related changes that affect pharmacokinetics and pharmacodynamics. For example, doses of renally cleared drugs (eg, gabapentin, some antimicrobials, digoxin) should be adjusted in patients with renal impairment.. For example, doses of renally cleared drugs (eg, gabapentin, some antimicrobials, digoxin) should be adjusted in patients with renal impairment.
Generally, although dose requirements vary considerably from person to person, medications should be started at the lowest dose in older adults. Most medications have not been well studied in adults > 75 years of age (particularly those with multiple morbidity, multiple medication use, and/or frailty) and, as a result, overdose is common simply because of a lack of data of how to dose medications in these patients. Typically, starting doses of about one third to one half the usual adult dose are indicated when a medication has a narrow therapeutic index, when another condition may be exacerbated by a medication, and particularly when patients are frail. The dose is then titrated upward as tolerated to the desired effect. When the dose is increased, patients should be evaluated for adverse effects, and drug levels should be monitored when possible.
Overdosage can also occur when drug interactions increase the amount of drug available or when different clinicians prescribe a medication and are unaware that another clinician prescribed the same or a similar medication (therapeutic duplication). Patients using only one pharmacy increases the likelihood of identifying and preventing therapeutic duplication.
Poor communication
Poor communication of medical information at transition points (from one health care setting to another) causes many drug errors and adverse drug effects in the hospital. When patients are discharged from the hospital, medication regimens that were started and needed only in the hospital (eg, sedative hypnotics, laxatives, proton pump inhibitors) may be unnecessarily continued by the discharging prescriber. Similarly, hospital formularies may dictate a change in a medication from one product to another during the stay (eg, statins) that can result in duplication or omission errors at discharge. Conversely, at admission to a health care facility, lack of communication may result in unintentional omission of a necessary maintenance medication. Medication reconciliation refers to a formal process of reviewing all prescribed medications at each transition of care and can help eliminate errors and omissions.
Underprescribing
Appropriate medications may be underprescribed—ie, not used for maximum effectiveness. Underprescribing may increase morbidity and mortality and reduce quality of life. Clinicians should use adequate drug doses and, when indicated, multidrug regimens.
Medications that are often underprescribed in older adults include those used to treat depression, Alzheimer disease, heart failure, post-myocardial infarction (beta-blockers), atrial fibrillation (anticoagulants), and hypertension. Also, immunizations are not always given as recommended.
Beta-blockers: In patients with a history of myocardial infarction and/or heart failure, even in older patients at high risk of complications (eg, those with pulmonary disorders or diabetes), these medications reduce mortality rates and hospitalizations.
Antihypertensives: Guidelines for treating hypertension in older adults are available, and treatment appears to be beneficial (reducing risk of stroke and major cardiovascular events) even in frail older adults. Nonetheless, studies indicate that hypertension is often not optimally controlled in older patients.
Drugs for Alzheimer disease: Acetylcholinesterase inhibitors and NMDA (N-methyl-d-aspartate) antagonists have been shown to benefit patients with Alzheimer disease. The amount of benefit is modest and variable, but patients and family members should be given the opportunity to make an informed decision about their use.
Anticoagulants: Anticoagulants (both warfarin and the newer direct oral anticoagulant drugs) reduce risk of stroke in patients with atrial fibrillation. Although there is an increased risk of bleeding with anticoagulation in general, some older adults who might benefit from anticoagulation are not receiving it. Anticoagulants (both warfarin and the newer direct oral anticoagulant drugs) reduce risk of stroke in patients with atrial fibrillation. Although there is an increased risk of bleeding with anticoagulation in general, some older adults who might benefit from anticoagulation are not receiving it.
Immunizations: Older adults are at greater risk of morbidity and mortality resulting from influenza, pneumococcal infection, respiratory syncytial virus, COVID-19, pertussis, and herpes zoster. Vaccination rates among older adults can still be improved.
In older patients with a chronic disorder, acute or unrelated disorders may be undertreated (eg, hypercholesterolemia may be untreated in patients with COPD [chronic obstructive pulmonary disease]). Clinicians may withhold these treatments because they are concerned about increasing the risk of adverse effects or the time required to benefit from treatment in a patient with reduced life expectancy. Clinicians may think that treatment of the primary problem is all patients can or want to handle or that patients cannot afford the additional medications. Patients and caregivers should be active participants in decision making about pharmacologic therapy so that clinicians can understand patients' priorities and concerns.
References
1. Zazzara MB, Palmer K, Vetrano DL, Carfì A, Onder G. Adverse drug reactions in older adults: a narrative review of the literature [published correction appears in Eur Geriatr Med. 2022 Feb;13(1):307. doi: 10.1007/s41999-021-00591-4.]. Eur Geriatr Med. 2021;12(3):463-473. doi:10.1007/s41999-021-00481-9
2. Tam VC, Knowles SR, Cornish PL, et al: Frequency, type and clinical importance of medication history errors at admission to hospital: a systematic review. CMAJ 173(5):510-5, 2005. doi: 10.1503/cmaj.045311
3. Wong JD, Bajcar JM, Wong GG, et al: Medication reconciliation at hospital discharge: evaluating discrepancies. Ann Pharmacother 42(10):1373-9, 2008. doi: 10.1345/aph.1L190
4. Forster AJ, Clark HD, Menard A, et al: Adverse events among medical patients after discharge from hospital. CMAJ 170(3):345-9.
5. The 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
6. Hanlon JT, Semla TP, Schmader KE, et al: Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug-disease interactions in the elderly quality measures. J Am Geriatr Soc 63(12): e8-e18, 2015. doi: 10.1111/jgs.13807
7. Innes GK, Ogden CL, Crentsil V, Concato J, Fakhouri TH. Prescription Medication Use Among Older Adults in the US. JAMA Intern Med. 2024;184(9):1121-1123. doi:10.1001/jamainternmed.2024.2781
8. Page RL 2nd, Ruscin JM. The risk of adverse drug events and hospital-related morbidity and mortality among older adults with potentially inappropriate medication use. Am J Geriatr Pharmacother. 2006;4(4):297-305. doi:10.1016/j.amjopharm.2006.12.008
Prevention
Before starting a new medication
To reduce the risk of adverse drug effects in older adults, clinicians should do the following before starting a new medication:
Consider that new symptoms or medical problems may be related to existing pharmacologic therapy
Consider nonpharmacologic treatment
Discuss goals of care with the patient and/or caregivers and establish a timeframe in which benefit from the pharmacologic therapy is expected
Evaluate the indication for each new medication (to avoid using unnecessary medications)
Consider age-related changes in pharmacokinetics or pharmacodynamics and their effect on dosing requirements
Choose the safest possible pharmacologic agent for the indication (eg, for noninflammatory arthritis, acetaminophen instead of an oral nonsteroidal anti-inflammatory drug [NSAID])Choose the safest possible pharmacologic agent for the indication (eg, for noninflammatory arthritis, acetaminophen instead of an oral nonsteroidal anti-inflammatory drug [NSAID])
Check for potential drug-disease and drug-drug interactions
Start with the lowest effective dose
Use the fewest medications necessary
Note coexisting disorders and their likelihood of contributing to adverse drug effects
Explain the uses and adverse effects of each medication
Provide clear instructions to patients about how to take their medications (including generic and brand names, spelling of each drug name, indication for each medication, and explanation of formulations that contain more than one medication) and for how long the medication will likely be necessary
Anticipate confusion due to sound-alike medication names and pointing out any names that could be confused (eg, Glucophage® and Glucovance®)
After starting a medication
The following should be done after starting a medication:
Assume a new symptom may be medication-related until proven otherwise (to prevent a prescribing cascade).
Monitor patients for signs of adverse drug effects, including measuring drug levels and doing other laboratory tests as necessary.
Document the response to therapy and increase doses as necessary to achieve the desired effect.
Regularly reevaluate the need to continue pharmacologic therapy and stop medications that are no longer necessary or medications with greater potential risk than benefit.
Ongoing
The following should be ongoing:
Medication reconciliation is a process that helps ensure transfer of information about medication regimens at any transition point in the health care system. The process includes identifying and listing all medications patients are taking (name, dose, frequency, route) and comparing the resulting list with the physician’s orders at a transition point. Medication reconciliation should occur at each move (admission, transfer, and discharge).
Computerized physician ordering programs and electronic medical record systems can incorporate prescribing alerts to warn clinicians to potential problems (eg, allergy, need for reduced dosage in patients with impaired renal function, drug-drug interactions). These programs can also cue clinicians to monitor certain patients closely for adverse drug effects.