Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Figures & data

Table 1 Fall-risk-increasing drugs in the literature

Category	Risk description and clinical management
CNS-acting agents	Retrospective case-control studies showed strong evidence of an association between substantially increased risk of falls and drugs from this therapy group. Patients receiving CNS-acting agents were ten times more likely to have fall risk (OR 9.90; 95% CI 1.6–60.63).^Citation8^–^Citation11 Inpatient falls were significantly associated with patients taking anti-Parkinson’s medication (OR about 4–5).^Citation10,Citation12
Cough preparations	Cough preparations are known to cause sedation and more frequent visits to the toilet, due to worsening bladder-outlet obstruction in elderly men. More fallers were taking cough mixture compared with nonfallers (5.7% versus 1.0%, P=0.001), indicating hospitalized patients on cough preparations were more likely to fall.^Citation13
NSAIDs	NSAID use was a significant predictor of falls in hospitalized elderly patients and was associated with a tenfold increase in the likelihood of falling (OR 10.02, 95% CI 2.6–38.58; P=0.001).^Citation14
Anti-Alzheimer’s agents	The use of Alzheimer’s medication (eg, donepezil, rivastigmine, galantamine, memantine) was associated with fall risk (HR 1.63, 95% CI 1.24–2.14; P=0.0005). Additional pharmacovigilance of the association between falls and Alzheimer’s medication use is warranted.^Citation6
Antiplatelet agents	A study in elderly Asian patients in an acute care setting, including 298 fallers and 298 matched nonfallers, indicated that hospitalized patients on antiplatelet agents were more likely to fall. More fallers were taking antiplatelet agents compared with nonfallers (15.9% versus 1.3%, P<0.001).^Citation13
Calcium antagonists	The probability of falls increased when patients used calcium antagonists (aOR 2.45, 95% CI 1.16–4.74; P=0.02).^Citation11
Diuretics	Nursing home residents are at an increased risk of falls on the day following a new prescription or increased dose of a loop diuretic drug (OR 2.46, 95% CI 1.02–5.92). It was estimated that for every 271 loop diuretic drug changes, one excess fall occurred. Extra precautions should be taken immediately following a loop diuretic drug change in an effort to prevent falls.^Citation15 A case-control study showed that current prescribing of thiazides was associated with an increased risk of falling, and that this was strongest in the 3 weeks following the first prescription (OR 4.28, 95% CI 1.19–15.42).^Citation16
α-blockers	Current use of standard-formulation α-blockers (prazosin, doxazosin, terazosin, alfuzosin, and tamsulosin) was associated with an increased risk of hip/femur fracture, commonly due to falls (aOR 1.9, 95% CI 1.1–3.0). The effect was particularly strong for first prescriptions (aOR 5.1, 95% CI 1.0–31.7) and during the first month of treatment (aOR 4.1, 95% CI 0.7–23.9). Stratification analysis according to indication of use showed that current use of α-blockers was not associated with hip/femur fracture in men with a diagnosis of benign prostatic hyperplasia, but was associated in men who used α-blockers for cardiovascular disease (aOR 2.8, 95% CI 1.4–5.4).^Citation17 No increased risk of fractures was associated with current use of modified-release doxazosin in hypertension, previous use, or the start of a treatment episode (≤28 days).^Citation18 Caution with respect to first-dose effects related to the initiation of a new episode of α-blocker treatment is advised, and modified-release doxazosin is a superior α-blocker versus standard formulation for the sake of avoiding fall risk in elderly patients.
Digoxin	Digoxin therapy (35% versus 22%) was more common in hospitalized elderly patients who had fallen than in control patients.^Citation19
Miscellaneous	Use of diabetes medications was significantly associated with an increased risk of falling (aOR 3.2, 95% CI 1.3–7.9)^Citation20 The rate of fall-related injuries for patients receiving a doublet of neurotoxic chemotherapy (9.15 per 1,000 person-months) was significantly higher than for those receiving a single neurotoxic agent (7.76 per 1,000 person-months) or a nonneurotoxic agent (5.19 per 1,000 person-months).^Citation7 Nasal preparations (eg, treatment of asthma or allergic rhinitis) (aOR 1.49, 95% CI 1.07–2.08) and antiglaucoma ophthalmic preparations (aOR 1.51, 95% CI 1.10–2.09) were statistically significantly associated with an emergency department visit due to a recurrent fall.^Citation5

Abbreviations: CNS, central nervous system (CNS-acting agents include benzodiazepines, sedatives, hypnotics, antidepressants, antipsychotic drugs, and anti-Parkinson drugs); NSAIDs, nonsteroidal anti-inflammatory drugs; OR, odds ratio; aOR, adjusted OR; HR, hazard ratio; CI, confidence interval.

Costa-DiasMJOliveiraASMartinsTMedication fall risk in old hospitalized patients: a retrospective studyNurse Educ Today20143417117623769987

 PubMed Web of Science ®Google Scholar

RhalimiMHelouRJaeckerPMedication use and increased risk of falls in hospitalized elderly patients: a retrospective, case-control studyDrugs Aging20092684785219761277

 PubMed Web of Science ®Google Scholar

ShutoHImakyureOMatsumotoJMedication use as a risk factor for inpatient falls in an acute care hospital: a case-crossover studyBr J Clin Pharmacol20106953554220573090

 PubMed Web of Science ®Google Scholar

TanakaMSuemaruKIkegawaYTabuchiNArakiHRelationship between the risk of falling and drugs in an academic hospitalYakugaku Zasshi20081281355136118758151

 PubMed Web of Science ®Google Scholar

MamunKLimJKAssociation between falls and high-risk medication use in hospitalized Asian elderly patientsGeriatr Gerontol Int2009927628119702938

 PubMed Web of Science ®Google Scholar

WalkerPCAlrawiAMitchellJFRegalREKhanderiaUMedication use as a risk factor for falls among hospitalized elderly patientsAm J Health Syst Pharm2005622495249916303905

 PubMed Web of Science ®Google Scholar

EpsteinNUGuoRFarlowMRSinghJPFisherMMedication for Alzheimer’s disease and associated fall hazard: a retrospective cohort study from the Alzheimer’s disease neuroimaging initiativeDrugs Aging20143112512924357133

 PubMed Web of Science ®Google Scholar

BerrySDMittlemanMAZhangYNew loop diuretic prescriptions may be an acute risk factor for falls in the nursing homePharmacoepidemiol Drug Saf20122156056322422651

 PubMed Web of Science ®Google Scholar

GribbinJHubbardRGladmanJRSmithCLewisSRisk of falls associated with antihypertensive medication: population-based case-control studyAge Ageing20103959259720650874

 PubMed Web of Science ®Google Scholar

SouvereinPCVan StaaTPEgbertsACDe la RosetteJJCooperCLeufkensHGUse of α-blockers and the risk of hip/femur fracturesJ Intern Med200325454855414641795

 PubMed Web of Science ®Google Scholar

HallGCMcMahonADComparative study of modified release alpha-blocker exposure in elderly patients with fracturesPharmacoepidemiol Drug Saf20071690190717443863

 PubMed Web of Science ®Google Scholar

GalesBJMenardSMRelationship between the administration of selected medications and falls in hospitalized elderly patientsAnn Pharmacother1995293543587633010

 PubMed Web of Science ®Google Scholar

KraussMJEvanoffBHitchoEA case-control study of patient, medication, and care-related risk factors for inpatient fallsJ Gen Intern Med20052011612215836543

 PubMed Web of Science ®Google Scholar

WardPRWongMDMooreRNaeimAFall-related injuries in elderly cancer patients treated with neurotoxic chemotherapy: a retrospective cohort studyJ Geriatr Oncol20145576424484719

 PubMed Web of Science ®Google Scholar

AskariMEslamiSSchefferACDifferent risk-increasing drugs in recurrent versus single fallers: are recurrent fallers a distinct population?Drugs Aging20133084585123959914

 PubMed Web of Science ®Google Scholar