Background Elderly patients are vulnerable to drug interactions because of age-related physiologic changes, an increased risk for disease associated with aging, and the consequent increase in medication use. Objective The purpose of this narrative review was to describe findings from rigorously designed observational cohort and case-control studies that have assessed specific drug interactions in elderly patients. Methods The PubMed and International Pharmaceutical Abstracts databases were searched for studies published in English over the past 10 years (December 2000–December 2010) using relevant Medical Subject Headings terms ( aged; aged, 80 and over; and drug interactions ) and search terms ( drug interaction and elderly ). Search strategies were saved and repeated through September 2011 to ensure that the most recent relevant published articles were identified. Additional articles were found using a search of review articles and reference lists of the identified studies. Studies were included if they were observational cohort or case-control studies that reported specific adverse drug interactions, included patients aged ≥65 years, and evaluated clinically meaningful end points. Studies were excluded if they used less rigorous observational designs, assessed pharmacokinetic/pharmacodynamic properties, evaluated drug-nutrient or drug-disease interactions or interactions of drug combinations used for therapeutic benefit (eg, dual antiplatelet therapy), or had inconclusive evidence. Results Seventeen studies met the inclusion criteria. Sixteen studies reported an elevated risk for hospitalization in older adults associated with adverse drug interactions. The drug interactions included: angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics, ACE inhibitors or angiotensin receptor blockers and sulfamethoxazole/trimethoprim, benzodiazepines or zolpidem and interacting medications, calcium channel blockers and macrolide antibiotics, digoxin and macrolide antibiotics, lithium and loop diuretics or ACE inhibitors, phenytoin and sulfamethoxazole/trimethoprim, sulfonylureas and antimicrobial agents, theophylline and ciprofloxacin, and warfarin and antimicrobial agents or nonsteroidal anti-inflammatory drugs. One study reported the risk for breast cancer-related death as a function of paroxetine exposure among women treated with tamoxifen. Conclusions Several population-based studies have reported significant harm associated drug interactions in elderly patients. Increased awareness and interventions aimed at reducing exposure and minimizing the risks associated with potentially harmful drug combinations are needed.

Potentially harmful drug-drug interactions in the elderly: a review.

Background
Criteria to assess the appropriateness of prescriptions might serve as a helpful guideline during professional training and in daily practice, with the aim to improve a patient’s pharmacotherapy.

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Inappropriate prescribing: a systematic overview of published assessment tools.

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Salicylate and salicyl conjugates: fluorimetric estimation, biosynthesis and renal excretion in man.

Purpose. The prevalence of 25 clinically important potential drug–drug interactions (DDIs) in a population represented by the drug claims database of a pharmacy benefit management company (PBM) was studied.

Methods. A retrospective cross-sectional analysis of pharmaceutical claims for almost 46 million participants in a PBM was conducted to determine the frequency of 25 DDIs previously identified as clinically important. A DDI was counted when drugs in potentially interacting combinations were dispensed within 30 days of each other during a 25-month period between April 2000 and June 2002.

Results. The number of DDIs ranged from 37 for pimozide and an azole antifungal to 127,684 for warfarin and a nonsteroidal antiinflammatory drug (NSAID). The highest prevalence (278.56 per 100,000 persons) and highest case-exposure rate (242.7 per 1,000 warfarin recipients) occurred with the warfarin–NSAID combination. The combination with the lowest overall prevalence (cyclosporine and a rifamycin, 0.10/100,000) differed from the combination with the lowest case-exposure rate (pimozide and an azole antifungal, 0.028 per 1,000 azole antifungal recipients). Number of cases, prevalence, and case-exposure rates for both sexes generally increased with age. An estimated 374,000 plan participants were exposed to a clinically important DDI during a 25-month period. Between 20% and 46% of prescription drug claims were reversed (canceled) for a medication with a drug interaction when a warning about the interaction was sent to the pharmacy.

Conclusion. Analysis of prescription claims data from a major PBM found that 374,000 of 46 million plan participants had been exposed to a potential DDI of clinical importance.

Assessment of potential drug–drug interactions with a prescription claims database

Background: Drug-drug interactions (DDIs) are preventable medical errors, yet exposure to DDIs continues despite systems that are designed to prevent such exposures. The purpose of this study was to examine pharmacy characteristics that may be associated with dispensed potential DDIs. Methods: This study combined survey data from community pharmacies in 18 metropolitan statistical areas with pharmacy claims submitted to 4 pharmacy benefit managers (PBMs) over a 3-month period from January 1, 2003 to March 31, 2003. Pharmacy characteristics of interest included prescription volume, the number of full-time equivalent pharmacists and pharmacy staff, computer software programs, and the ability to modify those programs with respect to DDI alerts, the use of technologies to assist in receiving, filling and dispensing medication orders, and prescription volume. The dependent variable in this study was the rate of dispensed medications that may interact. Results: A total of 672 pharmacies were included in the analysis. On average (SD), the respondents filled 1375 691 prescriptions per week, submitted 17,948 23,889 pharmacy claims to the participating PBMs, had 1.2 0.3 full-time equivalent pharmacists per hour open, and 545 (81%) were affiliated with a chain drug store organization. Factors significantly related to an increased risk of dispensing a potential DDI included pharmacist workload (odds ratio OR 1.03; 95% confidence interval CI 1.028‐1.048), pharmacy staffing (OR 1.10; 95% CI: 1.09‐1.11), and various technologies (eg, sophisticated telephone systems, internet receipt of orders, and refill requests) that assist with order processing, and the ability to modify DDI alert-screening sensitivity and detailed pharmacological information about DDIs. Conclusions: This study found that there was an increase in the risk of dispensing a potential DDI with higher pharmacist and pharmacy workload, use of specific automation, and dispensing software programs providing alerts and clinical information.

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Pharmacist workload and pharmacy characteristics associated with the dispensing of potentially clinically important drug-drug interactions

An improved method has been developed for the measurement of salicylic acid and salicyluric acid in blood plasma and for these two substances and salicyl glycuronates in urine. Older methods measured salicyluric acid by the different extraction efficiencies of two solvents and the weaker color formation of salicyluric acid with ferric nitrate. This method measures salicyluric acid more specifically by means of its marked fluorescence at p H 10. A low concentration of a fluorescent substance, probably salicyluric acid, which has not been reported previously was found in dog plasma following large doses of sodium salicylate. The rate of hydrolysis of salicyluric acid by concentrated hydrochloric acid, an important factor in the calculation of the salicyl glycuronate fraction in this and former methods, has been re-examined and a higher value than previously reported has been found. An explanation of this difference is suggested. A synthetic sample of the glycuronate of salicylic acid coupled through the phenolic hydroxyl group, which has not been isolated from urine in pure form, has been tested for reactivity in the method.

Ann M. Morgan

Papers

Determination of salicylic acid and two metabolites in plasma and urine using fluorimetry for directly measuring salicyluric acid.