ORIGINAL ARTICLES
Identification of Issues Related to Enteral Nutrients Using a Database of Near-miss Events from Community Pharmacies
2025 Volume 74 Issue 2 Pages 86-95
Details
2025 Volume 74 Issue 2 Pages 86-95
Undernutrition is a common risk after surgery or during periods when oral dietary intake is challenging. Enteral nutrients, frequently utilized in nutritional management, are drugs associated with multiple contraindications involving pathology and allergy, and they require careful attention in dispensing. However, the occurrence of nutrition-related incidents in community pharmacies remains unknown. This study aimed to identify issues regarding the safety of pharmacotherapy in patients requiring enteral nutrition using the database of Project to Collect and Analyze Pharmaceutical Near-Miss Event Information. We highlighted the critical information that pharmacists should focus on to prevent accidents and elucidated the details and prescription drugs of cases that matched the search for “Nutrition (all included)” in Japanese. There were 475 cases reported between January 2009 and September 2023. Of these, 347 cases (73%) were classified as “inquiry about prescription and provision of information to prescribing physician” (Category II) and 115 cases (24%) were classified as “drug dispensing” (Category I). In both cases, the top five drugs were enteral nutrients. Among the life-threatening Category II cases, 9 cases were for pathological contraindications including severe liver or renal dysfunction, 6 cases were for adverse reactions including diarrhea, and 5 cases were for allergies or patient constitutions. Notably, the incidence of adverse reactions was higher than in data for the latest annual reports. Therefore, pharmacists should be mindful while dealing with prescriptions involving possible contraindications in patients requiring enteral nutrition. Pharmacists should contribute to the provision of safe pharmacotherapy by remaining vigilant against dispensing errors.
The occurrence of patient harm caused by unsafe care is a significant global public health challenge. Therefore, healthcare professionals must be vigilant and proactive in identifying avoidable errors and adverse events. A previous meta-analysis involving 337,025 patients revealed that incidents related to drugs (25%) accounted for the largest proportion of preventable patient harm.1 Another meta-analysis demonstrated that approximately 1 in 30 patients are exposed to preventable drug harm in healthcare settings, and more than a quarter of this harm is considered severe.2 Unsafe care can lead to life-threatening situations, contributing to more than 3 million deaths every year.3 Therefore, the World Health Organization adopted the “Global Patient Safety Action Plan” at the 74th World Health Assembly in 2021. This action plan aims to ensure that every patient receives safe and respectful care, regardless of location or time.4
Patient harm from unsafe care has also been reported in Japan. In 1999, a surgical procedure was performed on the wrong patient, sparking heightened social concern regarding safety in healthcare settings. In the same year, a case was reported in which a patient died after a nurse mistakenly administered a disinfectant and heparinized saline solution intravenously. In 2000, a medication-related accident was reported in which a patient died after an oral medication was mistakenly injected into a blood vessel. In response to these incidents, the Ministry of Health, Labor, and Welfare (MHLW) designated 2001 as the “Year of Promoting Patient Safety” and decided to promote comprehensive patient safety measures. Therefore, the Japan Council for Quality Health Care (JCQHC) launched the “Project to Collect and Analyze Pharmaceutical Near-Miss Event Information” in 2009.5 By collecting and analyzing near-miss events from pharmacies, the project was designed to address the following objectives: to further promote patient safety by providing healthcare professionals in pharmacies and the general public with relevant information; to share information useful for developing preventive measures; and to widely disseminate the results of analyses.6 Heinrich’s law continues to serve as a poignant reminder for healthcare safety in Japanese medicine, illustrating that one serious accident is just the tip of the iceberg among 300 harmless human errors.7 Analyzing the existing information on several near-miss events is crucial to ensure the safety of pharmacotherapy and medical care. The database maintained by this project is freely accessible to the public, and information regarding individuals and medical institutions is completely anonymized. Examples of actual medical accidents involving drugs and diseases that are often overlooked can be collected using this database.
Nutrition plays an essential role in fostering both health and development.8 Undernutrition leads to various negative health consequences such as decreased muscle and bone mass, increased susceptibility because of weakened immune system, and delayed wound healing. According to the 2019 National Health and Nutrition Survey, the proportion of older individuals with undernutrition (body mass index ≤20 kg/m2) is approximately 13% for men and 21% for women.9
Undernutrition is more likely to occur in postoperative patients or patients with long-term difficulties with oral food intake. Nutritional therapy includes enteral and parenteral nutrition. Enteral nutrition is generally selected when the intestine is functional.10 Enteral nutrition can have multiple contraindications, including pathological contraindications, such as severe liver or renal dysfunction or end-stage renal failure, or contraindications related to milk protein allergy. Patients requiring nutritional management by enteral nutrition are often in a compromised or critical condition, and prescriptions including contraindications can lead to serious outcomes. For instance, patients with severe liver dysfunction are in danger of triggering coma because of insufficient protein metabolism. Patients with severe renal dysfunction also have difficulty in removing waste products from the body, including urea. Therefore, the administration of enteral nutrients containing nitrogen sources may enhance this tendency.
The number of older adults with declining swallowing function is increasing because of aging in Japan.11 Swallowing function plays a significant role in an individual’s ability to consume food orally, which directly affects the nutritional status. Considering these circumstances, the need for enteral nutrition is expected to climb in the future. To mitigate the risks of undernutrition and nutrition-based adverse events, it is imperative to consider the safety profiles of enteral nutrients administered to patients. Especially in Japan, with its aging population, the importance of safe healthcare for older adults must be emphasized. However, the occurrence of nutrition-related incidents in community pharmacies remains unknown.
The present study aimed to identify issues related to the safety of pharmacotherapy based on nutrition-related incidents in community pharmacies. Information from near-miss events was also used to identify procedures to prevent patient harm.
The JCQHC database for the Project to Collect and Analyze Pharmaceutical Near-Miss Event Information (https://www.yakkyoku-hiyari.jcqhc.or.jp/index.html) includes a case search function. For this study, we used the search term “Nutrition” in Japanese and set the filtering to “all included.” Reports from January 2009 to September 2023 were included. Any reports containing the word “Nutrition” were extracted for analysis. Both old-format reports (before 17 March 2020) and new-format reports were assessed. A representative example of a case report is presented in Figure 1. Data were classified into four categories established by the JCQHC based on the type of near-miss events: (I) drug dispensing; (II) inquiry about prescription and provision of information to prescribing physician; (III) designated insured medical material; and (IV) over-the-counter (OTC) drug sales (Table 1). Although the category names differ between the old and new reporting formats, the case details remained largely the same. We focused on two types of cases with the highest incidences (i.e., Category I and II) to determine the clinical issues at community pharmacies. Data were tabulated after categorizing the details in old-format reports according to the items designated in new-format reports. The factors considered for further analysis were patient attributes, details, and prescribed and related drugs. The JCQHC introduced data sub-categories in new-format reports, which prompted us to classify data in the old-format reports to match the new format. To capture the characteristics of the most common drugs in the present study, we collected the names of prescribed and related drugs in the reports and determined their frequency based on the number of times they were reported. Furthermore, we analyzed patient information including age and sex for cases involving the top five drugs to identify trends in the occurrence of problems. The population was the same as that identified in the search results, with no differences between the two analysis sections. All analyses were conducted using Microsoft Excel, including simple tabulation and Chi-square independence tests. Statistical significance was recognized for P < 0.05.
Example of a case report in the new format, based on a search using the keyword “Nutrition.”
| Category | New format | Old format |
|---|---|---|
| I | Drug dispensing | Drug dispensing |
| II | Inquiry about prescription and provision of information to prescribing physician | Inquiry about prescription |
| III | Designated insured medical material | Designated insured medical material |
| IV | OTC drug sales | Drug sales |
OTC: over the counter.
To identify issues related to nutrition, we first classified the data obtained from the search on the word “Nutrition.” We found a total of 475 cases, with 283 cases in the new format and 192 cases in the old format. Of these, 347 cases (73%) were related to Category II, 115 cases (24%) to Category I, 11 cases (2.3%) to Category IV, and 2 cases (0.42%) to Category II (Fig. 2A). The reports included 201 men, 271 women, and 3 individuals of unknown gender status (Fig. 2B). Of the 475 patients, 358 were aged 60 years or older (75%).
Case reports and patient attributes in near-miss events of nutrition.
(A) The number of near-miss events reported in the Project to Collect and Analyze Pharmaceutical Near-Miss Event Information. The search term was “Nutrition” in Japanese and the filtering was set to “all included” from January 2009 to September 2023. A total of 475 cases in both new and old formats were found. The events were categorized into: drug dispensing (Category I); inquiry about prescription and provision of information to prescribing physician (Category II); designated insured medical material (Category III); and over-the-counter (OTC) drug sales (Category IV). (B) The number of patient attributes (age and sex) in all case reports. The gender status of three individuals was unknown.
The details of Category II are listed in Table 2. Although these details included many different sub-categories, the most common sub-category was “dosage,” with 52 cases (15%). Table 3 lists the details of Category I. These Category I cases were categorized into four types based on the dispensing procedure: before dispensing, 11 cases (9.6%); dispensing and verification, 82 cases (71%); drug providing, 18 cases (16%); and after drug providing (home medical care), 4 cases (3.5%). In addition, we compared the proportion of all cases from the latest annual reports (2022) with our obtained data to understand the trends in nutrition-related cases. The number of reports on medication adherence (ability of medication) was more than four times higher than all reports from 2022 in Category II. Meanwhile, neglecting to dispense medication had more than seven times more reports than all reports from 2022 in Category I. In several sub-categories such as contamination with a foreign object, where the count was 0, particular attention and efforts by pharmacists were observed. No sex differences or age characteristics are listed in Tables 2 and 3.
| Sub-category | Nutrition-related reports | All reports in 2022 |
|---|---|---|
| Dosage | 52 (15) | 24,407 (25) |
| Drug name | 27 (7.8) | 4596 (4.6) |
| Adverse reactions | 25 (7.2) | 2301 (2.3) |
| Medication adherence (ability of medication) | 23 (6.6) | 1366 (1.4) |
| Pathological contraindication | 20 (5.8) | 6891 (6.9) |
| Living status | 18 (5.2) | 561 (0.56) |
| Change in physical conditions | 17 (4.9) | 1113 (1.1) |
| Interactions | 16 (4.6) | 5824 (5.9) |
| Usage | 15 (4.3) | 8413 (8.5) |
| Leakage of prescription | 13 (3.7) | 2700 (2.7) |
| Duplication of same ingredients | 12 (3.5) | 9428 (9.5) |
| Duplication of same efficacy drugs | 12 (3.5) | 14,305 (14) |
| Compatibility | 6 (1.7) | 371 (0.37) |
| Allergy or patient’s constitution | 6 (1.7) | 2317 (2.3) |
| History of adverse reactions | 6 (1.7) | 6150 (6.2) |
| Management of leftover drugs | 4 (1.2) | 699 (0.70) |
| Polypharmacy | 4 (1.2) | 124 (0.12) |
| Administration period | 3 (0.86) | 2456 (2.5) |
| Careless long-term administration | 2 (0.58) | 231 (0.23) |
| Incomplete requirements | 0 (0) | 527 (0.53) |
| Other | 66 (19) | 4644 (4.7) |
| Total | 347 (100) | 99,424 (100) |
Data given as number (percentage).
| Dispensing procedure | Sub-category | Nutrition-related reports | All reports in 2022 |
|---|---|---|---|
| Before dispensing | |||
| Data entry error | 11 (9.6) | 1876 (9.3) | |
| Dispensing and verification | |||
| Wrong strength/dosage form | 16 (14) | 3178 (16) | |
| Drug mix-up (different ingredients) | 14 (12) | 2542 (13) | |
| Wrong quantity | 13 (11) | 2856 (14) | |
| Failure to dispense | 8 (7.0) | 244 (1.2) | |
| Drug mix-up (same ingredients) | 6 (5.2) | 2279 (11) | |
| Expiration | 5 (4.3) | 69 (0.34) | |
| Error in one dose packets | 1 (0.87) | 837 (4.1) | |
| Wrong information on package sheet | 1 (0.87) | 170 (0.84) | |
| Error in weighing or packing | 0 (0) | 380 (1.9) | |
| Contamination with foreign object | 0 (0) | 78 (0.39) | |
| Other | 18 (16) | 2965 (15) | |
| Providing the drug | |||
| Neglecting to dispense medication | 11 (9.6) | 314 (1.3) | |
| Inadequate explanation | 2 (1.7) | 259 (1.3) | |
| Error in medication notebooks or record | 1 (0.87) | 201 (0.99) | |
| Patient misidentification | 0 (0) | 177 (0.87) | |
| Wrong explanation | 0 (0) | 96 (0.47) | |
| Wrong description on medication bag | 0 (0) | 311 (1.5) | |
| Other | 4 (3.5) | 925 (4.6) | |
| After providing the drug (home medical care) | |||
| Neglect to check after medication | 1 (0.87) | 99 (0.49) | |
| Error in setting for calendar | 0 (0.55) | 112 (0.55) | |
| Other | 3 (2.6) | 287 (1.4) | |
| Total | 115 (100) | 20,255 (100) | |
Data given as number (percentage).
In Category II, 262 types of drugs were detected with a frequency of 427. The prescribed and related drugs are shown in Figure 3A, with drugs reported two times or fewer not shown. The top 5 drugs with the highest number of cases were all enteral nutrients, accounting for 23% (99/427) of the reports. For Category I, 83 types of prescribed and related drugs were identified, which were reported 142 times in total (Fig. 3B). Drugs reported only once are not shown. Again, the top 5 drugs in this type were all enteral nutrients, accounting for 33% (47/142) of the cases. Therefore, we separately calculated the details (99 cases) of applicable cases to understand the details involving the top 5 enteral nutrients. Of these, we focused on three items related to enteral nutrients (contraindication, adverse reaction, and allergy) to ascertain safe pharmacotherapy. Among the life-threatening cases, 9 with pathological contraindications, 6 with adverse reactions, and 5 with allergies or patient constitutions were reported as specifics involving the top five enteral nutrients (Table 4). In particular, the results of pathological contraindications and allergies or patient’s constitution were stated as contraindications in the package inserts of each drug.
Prescription drugs and other related drugs included in near-miss events.
Prescription and related drugs were calculated based on the number of times they were reported. If multiple drugs were mentioned within a single report, the total count was calculated for the number of drugs mentioned. (A) The number of times these drugs were reported in inquiry about prescription and provision of information to prescribing physician (Category II). Data not shown for drugs reported two times or fewer. (B) The number of times these drugs were reported in drug dispensing (Category I). Data not shown for drugs reported only once.
| Drug | Specifics | Reports (n) | Details |
|---|---|---|---|
| ENSURE®︎ H | |||
| Pathological contraindications | 2 | End-stage renal failure | |
| Adverse reactions | 2 | Worsening renal disease, hemorrhagic diathesis and hypotension caused by interactions | |
| Allergies or patient constitution | 3 | Milk allergy, diarrhea, soybean allergy | |
| ENSURE LIQUID®︎ | |||
| Adverse reactions | 1 | Diarrhea | |
| RACOL®︎-NF Liquid for Enteral Use | |||
| Pathological contraindications | 1 | Severe renal dysfunction | |
| Adverse reactions | 2 | Diarrhea, hypoglycemia | |
| Allergies or patient constitution | 1 | Milk allergy | |
| RACOL®︎-NF Semi Solid for Enteral Use | |||
| Allergies or patient constitution | 1 | Milk allergy | |
| ENORAS®︎ Liquid for Enteral Use | |||
| Pathological contraindications | 6 | Severe renal dysfunction, severe liver dysfunction | |
| Adverse reactions | 1 | Diarrhea | |
Pathological contraindications were observed in six reports on ENORAS®︎ Liquid for Enteral Use, two reports on ENSURE®︎ H, and one report on RACOL®︎-NF Liquid for Enteral Use. These contraindications were related to severe renal or liver dysfunction in the patients. In these cases, a combined lack of confirmed ingredient composition and medical history was found to be the cause of the problem. Furthermore, inadequate confirmation of renal dysfunction as a pathological contraindication led to issues. Adverse reactions were found in two reports using ENSURE®︎ H, two reports using RACOL®︎-NF Liquid for Enteral Use, one report using ENSURE LIQUID®︎, and one report using ENORAS®︎ Liquid for Enteral Use. The most frequently reported adverse reaction was diarrhea. The causes were reported to be the patient’s medical condition and lack of coordination with medical institutions. Other adverse reactions included hemorrhagic diathesis and hypotension caused by drug interactions, as well as hypoglycemia. These cases were insufficient for understanding electrolyte content, poor nutritional status, and incorrect usage, because they lacked coordination among healthcare professionals. Allergies or patient constitutions were associated with three reports on ENSURE®︎ H, one report on RACOL®︎-NF Liquid for Enteral Use, and one report on RACOL®︎-NF Semi Solid for Enteral Use. The most common case was milk allergy. The causes were the patient’s medical condition and lack of coordination with medical institutions. In addition, soybean allergy reaction was caused by a lack of understanding of drug information.
Patient attributes of cases involving the top five enteral nutrientsWe classified patients into two age groups (0s–50s and 60s–100s) and analyzed the age groups in which the five enteral nutrients were most frequently reported using a Chi-square independence test (P < 0.05). ENSURE®︎ H was significantly reported among older individuals, whereas RACOL®︎-NF Liquid for Enteral Use was frequently reported in the younger age group (Table 5). We also analyzed whether the five enteral nutrients were more frequently reported in men or women using a Chi-square independence test (P < 0.05). ENSURE®︎ H had a significantly high incidence in women.
| Top five drugs | Age groups | P value | Sex groups | P value | |||
|---|---|---|---|---|---|---|---|
| 0s–50s (n=26) |
60s–100s (n=119) | Male (n=57) |
Female (n=88) |
||||
| ENSURE®︎ H | 2 (7.7) | 37 (31) | 0.015* | 11 (19) | 28 (32) | 0.001* | |
| ENSURE LIQUID®︎ | 8 (31) | 27 (23) | 0.383 | 14 (25) | 21 (24) | 0.924 | |
| RACOL®︎-NF Liquid for Enteral Use | 11 (42) | 24 (20) | 0.017* | 15 (26) | 20 (23) | 0.622 | |
| RACOL®︎-NF Semi Solid for Enteral Use | 4 (15) | 16 (13) | 0.795 | 11 (19) | 9 (10) | 0.122 | |
| ENORAS®︎ Liquid for Enteral Use | 1 (3.8) | 15 (13) | 0.197 | 6 (11) | 10 (11) | 0.875 | |
Data given as number (percentage). Cases involving the top five drugs represent a subset of patient attributes. The population is the same as the population identified in the search results.
*P < 0.05 (Chi-square independence test).
This study analyzed the safety of nutrition pharmacotherapy using a database of near-miss events in community pharmacies. We analyzed two major types of reports in this study, Category II and Category I, which accounted for 73% and 24% of the cases, respectively (Fig. 2A). The latest annual report (2022) of near-miss events showed that there were 99,424 (83%) reports related to Category II, 20,255 (17%) reports related to Category I, 86 (0.072%) reports related to Category IV, and 92 (0.077%) reports related to Category III, out of a total of 119,857 reports.12 Our data from nutrition-related reports revealed a slightly increased prevalence of Category I compared with the 2022 overall dataset. Remarkably, within the sub-categories, adverse reaction-related nutrition was 7.2% compared with 2.3% in the 2022 overall dataset (Table 2). This data indicates a strong association between nutrition and adverse reactions. However, incidents of Category I distribution appeared to be typical medication errors (Table 3). As a further characteristic of reports related to nutrition, over 70% of the cases were of older adults aged 60 years and older (Fig. 2B), suggesting the importance of nutrition in older individuals.
To identify further issues, we analyzed prescription and other related drugs in the reports. As expected, the top five drugs in Category I involved enteral nutrients (Fig. 3). The information in package inserts states that enteral nutrients are used for maintaining the nutritional health of postoperative patients or for tube feeding, especially in patients that experience difficulty in oral intake over a long period.13 In a previous study that surveyed community pharmacies in Osaka regarding the use of enteral nutrients, 47% of pharmacists were found to have experience in providing medication guidance for enteral nutrients (excluding oral intake).14 Therefore, enteral nutrients are considered an important drug frequently used not only for postoperative nutritional management but also for nutritional management for older individuals in a community. This is reflected by the fact that enteral nutrients were often involved in the reported cases.
Errors in drug choice may lead to potentially life-threatening situations, particularly in older adults. Our research showed that near-miss events related to nutrition, as well adverse reactions, are more common in older individuals (Fig. 2B). Furthermore, the absence of information on patients’ allergy histories and contraindications for enteral nutrients also warrants attention. ENORAS®︎ Liquid for Enteral Use was the most reported enteral nutrient associated with pathological contraindication, including severe renal and liver dysfunction (Table 4). Patients with poor nutritional status often have chronically inadequate caloric intake. ENORAS®︎ Liquid for Enteral Use has an energy content of 1.6 kcal/mL, the highest among the top five enteral nutrients. This was followed by ENSURE®︎ H, which contains 1.5 kcal/mL.15 It is possible that the number of calories consumed is often emphasized, overlooking the pathological contraindication while prescribing enteral nutrients. Among adverse reactions, diarrhea was the most reported condition (Table 4). According to the guidelines for parenteral and enteral nutrition, diarrhea is one of the complications that healthcare providers need to consider when administering enteral nutrients.Circulatory dynamics or electrolyte abnormalities caused by diarrhea in older adults may aggravate their general condition. Clinical trials conducted in Japan on patients who have difficulty with oral diet, prior to the approval of ENSURE LIQUID®︎, found that diarrhea was the most common adverse reaction, occurring in 43 of 61 cases.16 Guidelines for the use of parenteral and enteral nutrition indicate that diarrhea is the most common gastrointestinal complication, occurring in 21%–72% of patients receiving enteral nutrition, and cite administration method as a factor causing diarrhea.10 The package insert for ENSURE LIQUID®︎ (https://www.abbott.co.jp/content/dam/corp/abbott/ja-jp/our-products/ani/ENS-AttacedFile-ver-3.pdf) includes a precaution stating that the concentration should be temporarily decreased to approximately 0.5 kcal/mL if any adverse reaction, such as diarrhea, occurs until the condition is alleviated.13 Among allergies or patient constitutions, milk allergy was the most common concern (Table 4). Milk allergy is specified as a contraindication in the package insert, because milk casein may induce shock or anaphylaxis.15 In fact, there have been reported cases of anaphylaxis after ENSURE®︎ H administration.17 Furthermore, a case of soy allergy was also found. Therefore, not only healthcare professionals involved in patient care, but also patients themselves, must understand the interaction between enteral nutrition and allergies. Among the cases involving the top five drugs, it was found that reports were significantly higher for ENSURE®︎ H among older individuals or women (Table 5). Based on the characteristics of the database, we anticipated that drugs with the highest number of reported cases would also have the highest prescription rates. Women may have chosen high calorie options such as ENSURE®︎ H because they can only drink a small amount. Therefore, community pharmacists must always try to obtain the latest information by interviewing patients and be mindful of adverse reactions, contraindications, and allergies associated with enteral nutrients. Furthermore, pharmacists need to utilize information on allergy details and medical history, which is present in medication notebooks, and actively share the patient’s condition with other healthcare professionals, including prescribing physicians.
This study has a number of limitations. Given that our case search was based on the keyword “Nutrition,” we might not have extracted all cases of patients who were prescribed enteral nutrients. There is also the possibility of reporting bias in the case reports for this project, because they were based on spontaneous reporting. In addition, the reported cases may have included adverse events that were not reported, and some reports may have included inaccurate content.
In this study, we investigated issues regarding the safety of pharmacotherapy in patients requiring enteral nutrition based on a database of near-miss events in community pharmacies. We found that enteral nutrients were the top prescribed and related drugs in cases of Category II. Among these cases, pathological contraindications were ranked third in terms of specifics related to enteral nutrients. Enteral nutrients were also the top prescribed and related drugs in cases of Category I, indicating that they were prone to dispensing errors. In clinical practice, nutritional management is closely associated with pharmacotherapy, but there is limited research on nutritional interventions and issues. The present findings provide the first evidence of the challenges in nutritional management in community pharmacies and the appropriate use of related drugs.
We thank the JCQHC office for providing this database free of charge and for kindly granting us permission to publish it. We also thank Editage for English language editing.
The authors have declared that no conflict of interest exists.
