Evaluation of the Potential Acetylcholinesterase Inhibitor‐Induced Rhinorrhea Prescribing Cascade

Abstract

To the Editor: The most commonly used medications for patients with dementia are acetylcholinesterase inhibitors (AChEIs; donepezil, rivastigmine, galantamine). 1 Use of these medications are often limited by adverse events (AEs) including nausea, vomiting, diarrhea, incontinence, hypersalivation, sweating, lacrimation, rhinorrhea, and bronchorrhea. 1-3 In particular, rhinorrhea is not a well-recognized AE of AChEI and was only previously documented in a meta-analysis of randomized controlled trials of donepezil. 4 This AE may result in a prescribing cascade (PC) in which AChEI-induced rhinorrhea results in the use of a rhinorrhea medication rather than discontinuation or a dose reduction of AChEI. 5 The AChEI-induced rhinorrhea PC has not been described beyond a case report. 6 We aimed to assess this PC using a sample of patient visits from the United States.We used the 2014 and 2015 National Ambulatory Medical Care Survey (NAMCS) data that comprises medications from providers' notes including prescription and over-thecounter (OTC) products. Patient visits included those aged 55 years and older and treated with an antidementia medication (AChEI or memantine, an N-methyl-D-aspartate [NMDA] antagonist). We compared AChEI users (AChEI with or without memantine) with non-AChEI users (memantine only) because memantine is not associated with rhinorrhea. 7 We assessed the co-use of rhinorrhea medications (RMs; ie, medications used to treat rhinorrhea) that served as markers for a potential AChEI-induced rhinorrhea PC. RMs included firstgeneration histamine 1 (H 1 )-blockers, second-generation H 1 blockers, nasal anticholinergics, nasal glucocorticoids, and montelukast, a leukotriene antagonist (full list available on request). 8 We adjusted for age, sex, race, geographic region, year, comorbidities, and number of concomitant medications excluding RMs. 9 Data were analyzed using the sampling visit weights that were used to produce national estimates and account for survey clustering. We compared the percentage of visits in which RMs were used among AChEI users vs non-AChEI users. Weighted odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate univariate and multivariable analyses. We also estimated the percentage of patient visits impacted by the AChEI-induced rhinorrhea PC by subtracting the percentages of AChEI users from non-AChEI users who co-used RMs.There were an estimated 14 743 000 (95% CI = 11 493 000-17 993 000) patient visits in which a patient aged 55 years or older was taking an antidementia medication (using weighted estimates). Among antidementia medication user visits, 85.6% (n = 12 606 000) were taking an AChEI (with donepezil the most common [n = 10 813 000]). Memantine was used in

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

“…The rhinorrhea medications consist of antihistamine, nasal anticholinergics and nasal glucocorticoids. 178 These co-medications may contribute to negative side effects. Therefore, physicians should consider dose reduction of AChEIs instead of adding other medications to treat adverse effects of AChEIs.…”

Prescribing cascades in ambulatory care: A structured synthesis of evidence

“…Figure 1 shows that of 103 articles included in our previous systematic review, 18 three used the same database to investigate a single prescribing cascade at different points in time, 24–26 of which we only selected the most recent 26 . Six further studies only reported exploratory studies, 27–32 five only reported cross‐sectional studies, 5,33–36 and nine articles did not find any significant positive associations between index and marker drugs 37–45 . The remaining 81 articles reported 99 prescribing cascades (i.e., distinct combinations of index and marker drugs).…”

A Prescribing Cascade of Proton Pump Inhibitors Following Anticholinergic Medications in Older Adults With Dementia

“…The prescribing cascade was defined as existing when an adverse drug event (ADE) was misinterpreted as a new medical condition that resulted in a new medication being prescribed to treat the ADE ( Rochon and Gurwitz, 1995 ; Rochon and Gurwitz, 2017 ; McCarthy et al, 2019 ). Prescribing cascades can affect people of any age ( Gill et al, 2005 ; Vouri et al, 2018 ; Huh et al, 2019 ; Vouri et al, 2020 ) but have been found to occur more frequently in older adults ( Rochon and Gurwitz, 2017 ; McCarthy et al, 2019 ). This is due in part to increased polypharmacy among older compared to younger adults which increases exposure to drugs that potentially initiate the prescribing cascade ( Beijer and de Blaey, 2002 ; Canadian Institute for Health Information, 2018 ).…”