Prevalence of potentially harmful multidrug interactions on medication lists of elderly ambulatory patients

Background It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. Methods Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. Results MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. Conclusions An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.

Detection of adverse drug events in e-prescribing and administrative health data: a validation study

Background Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection. Methods We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons. Results Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0–95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician. Conclusion Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications.

Adverse Drug Events due to Central Nervous System Depressant Drugs in Pediatric Patients With or Without Surgery

OBJECTIVES To identify differences in the incidence and severity of adverse drug events (ADEs) due to CNS depressant drugs among pediatric patients with and without surgery. METHODS The Japan Adverse Drug Events Study was a cohort study enrolling pediatric inpatients. Potential ADEs were identified by onsite review of medical charts, incident reports, and prescription queries. Two independent physicians classified ADEs and severity. We compared the incidence and characteristics of ADEs between pediatric patients with surgery (surgery group) and without surgery (non-surgery group). We evaluated severity of ADEs due to CNS depressant drugs among both groups. RESULTS We enrolled 944 patients, 234 in surgery group and 710 in non-surgery group. A total of 480 ADEs due to any drugs occurred in 225 patients. Among 81 ADEs due to CNS depressant drugs, 42 ADEs were in surgery group, whereas 39 were in non-surgery group. The risk of fatal or life-threatening ADEs due to CNS depressant drugs was significantly higher than other drugs (12% vs. 2%, p < 0.001). In the surgery group, anesthetics led to 2 fatal or life-threatening, 8 serious, and 30 significant ADEs, whereas in the non-surgery group anesthetics led to 2 fatal or life-threatening, 5 serious, and 4 significant ADEs. Anesthetics were higher risk in the non-surgery group (p = 0.049). CONCLUSIONS The risks of fatal and life-threatening ADEs were significantly higher with CNS depressant drugs than other drugs. Pediatric patients without surgery have higher risks of fatal or life-threatening ADEs due to anesthetics than those with surgery.

Sex differences in text-mined possible adverse drug events associated with drugs for psychosis

Background: Understanding sex differences in adverse drug reactions to drugs for psychosis could potentially guide clinicians in optimal drug choices. Aims: By applying a text-mining approach, this study aimed to investigate the relationship between drugs for psychosis and biological sex differences in frequencies and co-occurrences of potential adverse drug events (ADEs). Methods: Electronic patient records of a psychiatric population (1427 men and 727 women) were text mined for potential ADEs. The relative risk of experiencing specific ADEs and co-occurrence of ADEs were calculated for each sex. Results: Findings included 55 potential ADEs with significantly different frequencies between the two sexes. Of these, 20 were more frequent in men, with relative risks of 1.10–7.64, and 35 were more frequent in women, with relative risks of 1.19–21.58. Frequent potential ADEs were psychiatric symptoms, including sexual dysfunction and disturbances in men, and gastrointestinal symptoms, suicidal and self-injurious behaviour and hyperprolactinemia-related events in women. Mention of different hyperprolactinemia-related ADEs often co-occurred in female patients but not in male patients. Conclusion: Several known sex-related ADEs were identified, as well as some previously not reported. When considering the risk–benefit profile of drugs for psychosis, the patient’s sex should be considered.

Study of adverse drug reactions in a tertiary care hospital

Background: The objectives of the study were to evaluate incidence and preventability of adverse drug events (ADEs) and potential ADEs and to analyse preventable events to develop prevention strategies.Methods: The study was retrospective observational study conducted at a rural tertiary care hospital at Maharashtra, for 12 months. Patients of both gender and all age group were included in the study. These entire adverse drug reactions were reported either by the PVPI assistance and/or hospital staff and their severity and causality assessments was performed as per Naranjo’s and Hartwig’s assessment criteria respectively. Data was analyzed by using Microsoft Excel.Results: There were total 256 ADR (adverse drug reactions) were reported in 12 months from January 2018 to December 2018 in various departments of the study center. Most of the adverse drug reactions were reported among age group of 21–40 years patients. Rash and itching (69) were most commonly reported ADR’s. ART (31.25%), antibiotics (28.90%) were reported to induce maximum number of ADRs. Most of the adverse drug reactions were possible (194, 75.78%) and mild (208, 81.25%) in nature.Conclusions: The antibiotics, ART drugs were most common drugs to reported ADRs. The commonly reported reactions were rash and itching.

Cost-effectiveness analysis of a hospital electronic medication management system

Objective To conduct a cost–effectiveness analysis of a hospital electronic medication management system (eMMS). Methods We compared costs and benefits of paper-based prescribing with a commercial eMMS (CSC MedChart) on one cardiology ward in a major 326-bed teaching hospital, assuming a 15-year time horizon and a health system perspective. The eMMS implementation and operating costs were obtained from the study site. We used data on eMMS effectiveness in reducing potential adverse drug events (ADEs), and potential ADEs intercepted, based on review of 1 202 patient charts before (n = 801) and after (n = 401) eMMS. These were combined with published estimates of actual ADEs and their costs. Results The rate of potential ADEs following eMMS fell from 0.17 per admission to 0.05; a reduction of 71%. The annualized eMMS implementation, maintenance, and operating costs for the cardiology ward were A$61 741 (US$55 296). The estimated reduction in ADEs post eMMS was approximately 80 actual ADEs per year. The reduced costs associated with these ADEs were more than sufficient to offset the costs of the eMMS. Estimated savings resulting from eMMS implementation were A$63–66 (US$56–59) per admission (A$97 740–$102 000 per annum for this ward). Sensitivity analyses demonstrated results were robust when both eMMS effectiveness and costs of actual ADEs were varied substantially. Conclusion The eMMS within this setting was more effective and less expensive than paper-based prescribing. Comparison with the few previous full economic evaluations available suggests a marked improvement in the cost–effectiveness of eMMS, largely driven by increased effectiveness of contemporary eMMs in reducing medication errors.