Benzonatate Exposure Trends and Adverse Events.

BACKGROUND AND OBJECTIVES: Adverse events (AE), including death, occur in children with benzonatate use. This study aims to understand recent trends in benzonatate exposure and clinical consequences in pediatric patients. METHODS: This retrospective analysis of data from IQVIA pharmacy drug dispensing, National Poison Data System, National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project, FDA Adverse Event Reporting System, and the medical literature evaluated exposure trends and medication-related AEs with benzonatate. Trends for comparator narcotic and nonnarcotic antitussive medications were analyzed where possible for context. RESULTS: During the study period, pediatric benzonatate prescription utilization increased but remained low compared with pediatric utilization of dextromethorphan-containing prescription antitussive medications. Among the 4689 pediatric benzonatate exposure cases reported to US poison control centers from 2010 to 2018, 3727 cases (80%) were for single-substance exposures. Of these, 3590 cases (77%) were unintentional exposures and most involved children 0 to 5 years old (2718 cases, 83%). Cases involving intentional benzonatate exposure increased among children 10 to 16 years old with a more pronounced increase for multiple-substance exposures. Most benzonatate cases involving misuse or abuse were for children 10 to 16 years old (59 cases, 61%). The proportion of cases with serious adverse effects was low. There were few cases annually of serious AEs with benzonatate in children. CONCLUSIONS: There were rising patterns of unintentional ingestion of benzonatate in children 0 to 5 years old and intentional benzonatate ingestion in children 10 to 16 years old. Rational prescribing and improved provider and caregiver awareness of benzonatate toxic effects may reduce risks associated with benzonatate exposure.

Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness. METHODS: We performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC. RESULTS: Compared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban. CONCLUSIONS: Among patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit-harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit-harm profile than rivaroxaban.

Use of tumor necrosis factor-alpha inhibitors during pregnancy among women who delivered live born infants.

PURPOSE: To describe the use of tumor necrosis factor-alpha inhibitors (TNFis) among pregnancies ending in a live birth and with a diagnosis of ankylosing spondylitis (AS), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ulcerative colitis (UC). METHODS: We identified pregnancies among women aged 15 to 54 years between 01/01/2004 and 09/30/2015 from 16 health plans participating in Sentinel. We inferred indication using ICD-9-CM codes in the 183-day period before conception. We assessed proportion of infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab by calendar year, indication, and maternal age, and compared them to proportions in an age-matched, indication-matched, and date-matched non-pregnant cohort. RESULTS: Among 19 681 pregnancies with at least one chronic inflammatory condition, 2990 (15.2%) received a TNFi. In both pregnancies and matched non-pregnant cohort, TNFi use was highest (34.4%; 55.8%) for PsA patients and lowest (6.2%; 13.4%) for PsO patients. Etanercept was most frequently used among AS/JIA/PsA/PsO/RA patients, while infliximab was the preferred TNFi for CD/UC patients. Except for infliximab and certolizumab, TNFi use during pregnancy decreased after the first trimester. Pregnancies among older pregnant women (45-54 years) were more likely to be treated compared with the matched non-pregnant cohort. CONCLUSION: There was a preference for etanercept among pregnancies with AS/JIA/PsA/PsO/RA, despite the availability of other TNFis. Decline in TNFi use after the first trimester may be related to the desire to reduce TNFis transplacental transfer and to minimize infection risk to the fetus or baby associated with live vaccine immunizations after birth.

Prospective surveillance pilot of rivaroxaban safety within the US Food and Drug Administration Sentinel System.

PURPOSE: The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance. METHODS: In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods. RESULTS: Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71). CONCLUSIONS: This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety.

Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice: A Retrospective Cohort Study.

BACKGROUND: Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited. OBJECTIVE: To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice. DESIGN: Retrospective cohort. SETTING: National U.S. Food and Drug Administration Sentinel network. PATIENTS: Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014. MEASUREMENTS: Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score-matched patients starting treatment with dabigatran or warfarin. RESULTS: Among 25 289 patients starting dabigatran therapy and 25 289 propensity score-matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran. LIMITATION: Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values). CONCLUSION: In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation. PRIMARY FUNDING SOURCE: U.S. Food and Drug Administration.

Antihypertensive drug associated angioedema: effect modification by race/ethnicity.

PURPOSE: Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. METHODS: New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts. RESULTS: Angioedema incidence rates (per 1000 person years) in beta-blocker users were 1.80 (whites), 4.11 (blacks), 1.89 (Asians), and 2.10 (Hispanics); in ACEI users, 4.03, 23.77, 2.94, and 4.27; and in ARB users, 1.73, 3.11, 1.10, and 1.90, respectively. Incidence rates were significantly higher in the first 30 days of exposure for all drug × race/ethnic groups. Overall, angioedema risk increased among ACEI users (hazard ratio, 2.91; 95% confidence interval, 2.75-3.07) but not ARB users (0.93, 0.85-1.02) versus beta-blocker users. Angioedema risk with ACEIs versus beta-blockers increased more in blacks (6.28, 5.44-7.24) than whites (2.33, 2.19-2.48), Hispanics (2.04, 1.36-3.07), and Asians (1.48, 0.94-2.35). Compared with white beta-blocker users, angioedema risk was increased 2.9-fold in whites, 20.2-fold in blacks, and 2.3-fold in other race/ethnic groups combined during the first 30 days of ACEI exposure. CONCLUSIONS: There was significant effect modification of angioedema risk by race and ACEI use for blacks, but not for other race/ethnicity groups. Angioedema risk was significantly greater in the first 30 days of exposure for all, and highest among blacks.

The US Food and Drug Administration's drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003-2012.

BACKGROUND: Emerging safety issues associated with long-acting beta2-agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. METHODS: We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved. RESULTS: There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. CONCLUSION: Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation.

Importance: Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. Objective: To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design, Setting, and Participants: Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Exposures: Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Main Outcomes and Measures: Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. Results: A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Conclusions and Relevance: Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation.

BACKGROUND: The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established. METHODS AND RESULTS: We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. CONCLUSIONS: In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Analysis of benzonatate overdoses among adults and children from 1969-2010 by the United States Food and Drug Administration.

STUDY OBJECTIVE: To augment the December 2010 United States Food and Drug Administration (FDA) Drug Safety Communication on accidental ingestion of benzonatate in children less than 10 years old by summarizing data on emergency department visits, benzonatate exposure, and reports of benzonatate overdoses from several data sources. DESIGN: Retrospective review of adverse-event reports and drug utilization data of benzonatate. DATA SOURCES: The FDA Adverse Event Reporting System (AERS) database (1969-2010), the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES, 2004-2009), and the IMS commercial data vendor (2004-2009). PATIENTS: Any patient who reported an adverse event with benzonatate captured in the AERS or NEISS-CADES database or received a prescription for benzonatate according to the IMS commercial data vendor. MEASUREMENTS AND MAIN RESULTS: Postmarketing adverse events with benzonatate were collected from the AERS database, emergency department visits due to adverse events with benzonatate were collected from the NEISS-CADES database, and outpatient drug utilization data were collected from the IMS commercial data vendor. Of 31 overdose cases involving benzonatate reported in the AERS database, 20 had a fatal outcome, and five of these fatalities occurred from accidental ingestions in children 2 years of age and younger. The NEISS-CADES database captured emergency department visits involving 12 cases of overdose from accidental benzonatate ingestions in children aged 1-3 years. Signs and symptoms of overdose included seizures, cardiac arrest, coma, brain edema or anoxic encephalopathy, apnea, tachycardia, and respiratory arrest and occurred in some patients within 15 minutes of ingestion. Dispensed benzonatate prescriptions increased by approximately 52% from 2004 to 2009. CONCLUSION: Although benzonatate has a long history of safe use, accumulating cases of fatal overdose, especially in children, prompted the FDA to notify health care professionals about the risks of benzonatate overdose. Pharmacists may have a role in preventing benzonatate overdoses by counseling patients on signs and symptoms of benzonatate overdose, the need for immediate medical care, and safe storage and disposal of benzonatate.

Use of parenteral iron products and serious anaphylactic-type reactions.

Controversy exists about the safety of the parenteral iron dextran products, Dexferrum and INFeD, which have been associated with rare, serious anaphylactic-type reactions. In the United States, their product labels carry boxed warnings of this adverse event; some have called for the withdrawal from marketing of the higher molecular weight Dexferrum. Between 2002 and 2007, sales of Dexferrum, INFeD, and iron gluconate Ferrlecit declined 32.5%, 21%, and 4.8%, respectively, while sales of iron sucrose Venofer increased 160%. Voluntary reports submitted to the Food and Drug Administration show anaphylactic reactions and symptoms for the four parenteral iron products. Because of underreporting, possible differential reporting, absence of iron dextran brand names, and incomplete use (denominator) data, incidence rates and relative risk estimates cannot be calculated. U.S. death certificate data show that for most years from 1979 through 2006, no more than 3 deaths per year were coded to "adverse events in therapeutic use of iron preparations;" brand names were not consistently recorded. Emergency department data show small numbers of visits for treatment of allergic reactions with intravenous iron preparations. The data presented herein show that allergic reactions are possible with all four parenteral iron products, and it is difficult to determine which product has the largest risk based on sales data, voluntarily submitted adverse event reports, death certificates, ED visits, and observational studies performed to date. To help differentiate risk among the parenteral iron products, the brand name of the product always should be provided on medical records, death certificates, and adverse drug reaction reports.

Measures of cognitive functioning in the 1994-2000 Second Longitudinal Study of Aging.

OBJECTIVES: This report describes in detail the measures of cognitive functioning administered in the Second Longitudinal Study of Aging (LSOA II) and proposes a three-category cognitive impairment variable for analysts' use that is derived from the individual measures. METHODS: LSOA II self-respondents completed an 11-question cognitive functioning measure based on the Telephone Interview of Cognitive Status (TICS) instrument. Proxy respondents answered nine questions drawn from the short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Using cut points provided in the literature as a guide, a single three-level categorical measure of cognitive impairment was created: probable, possible, and no cognitive impairment. RESULTS: The cognitive functioning measures administered in LSOA II retain many of the favorable psychometric properties of the original TICS and IQCODE. The constructed cognitive impairment (CI) variable demonstrates good construct validity, and prevalence rates are generally consistent with those from other published studies. CONCLUSIONS: The categorical CI variable is easy to use and interpret and allows analysts the option of combining self- and proxy-respondent data in investigations of associations between CI and health outcomes, including continuing independence, progressive impairment, health care utilization patterns, and mortality.

Payment source and length of use among home health agency discharges.

PURPOSE: Our study compared (1) length of use among home health care (HHC) discharges with Medicare, Medicaid, or private health insurance between 1991 and 2000 and (2) factors associated with length of HHC use among discharges with Medicare, Medicaid, or private health insurance. METHODS: Data were obtained from the 1992, 1994, 1996, 1998, and 2000 National Home and Hospice Care Surveys (n = 18,416). Logistic regressions and stratified analyses by primary payment source were applied. RESULTS: After adjusting for covariates, Medicare HHC patients were from 0.52 to 0.75 times less likely to be discharged within 30 days in 1991-1996 than in 1997-1998. Medicaid patients were 0.37 times less likely to be discharged within 30 days in 1991-1992 than in 1997-1998. Patients with private insurance were 2.05 times more likely to be discharged within 30 days in 1993-1994 than in 1997-1998. No significant difference in length of use was found at the multivariate level between 1997-1998 and 1999-2000 among HHC patients with Medicare, Medicaid, or private health insurance. Results for being discharged within 60 days were similar to these described above. CONCLUSIONS: Our study shows that length of HHC use among Medicare discharges decreased after the implementation of the Medicare interim payment system. We did not find a spillover effect of the Medicare interim payment system on length of HHC use among discharges with Medicaid or private health insurance. Our results can help health professionals and policy makers better understand the dynamic associations between payment systems and length of use of HHC services.

Inappropriate medication prescribing for elderly ambulatory care patients.

BACKGROUND: Inappropriate medication use in elderly patients has been linked to a large share of adverse drug reactions and to excess health care utilization. METHODS: Trends in the prevalence of potentially inappropriate drug prescribing at ambulatory care visits by elderly persons from 1995 to 2000 were examined with data from office-based physicians in the National Ambulatory Medical Care Survey and from hospital outpatient departments in the National Hospital Ambulatory Medical Care Survey. Explicit criteria were used to identify potentially inappropriate prescribing. Multivariate regression was used to identify related factors. RESULTS: In 1995 and 2000, at least 1 drug considered inappropriate by the Beers expert panel was prescribed at 7.8% of ambulatory care visits by elderly patients. At least 1 drug classified as never or rarely appropriate by the Zhan expert panel was prescribed at 3.7% and 3.8% of these visits in 1995 and 2000, respectively. Pain relievers and central nervous system drugs were a large share of the problem. The odds of potentially inappropriate prescribing were higher for visits with multiple drugs and double for female visits. The latter was due to more prescribing of potentially inappropriate pain relievers and central nervous system drugs. CONCLUSIONS: Potentially inappropriate prescribing at ambulatory care visits by elderly patients, particularly women, remains a substantial problem. Interventions could target more appropriate drug selection by physicians when prescribing pain relievers, antianxiety agents, sedatives, and antidepressants to elderly patients. Such behavior could eliminate a large portion of inappropriate prescribing for elderly patients and reduce its higher risk for women.