Pediatric Prescribers’ Knowledge of the Ew Meds^™ List and Taste Masking

From birth, infants demonstrate a preference for sweet taste and umami (savory) flavors, as well as a strong dislike of bitterness which may arise from the evolutionary imperative to find appropriate and non-toxic energy sources.^1,2  The US Food and Drug Administration defines palatability as “the quality of a drug product that makes it pleasant or acceptable in terms of taste, after-taste, smell, and texture” and is a critical factor in determining patient acceptance of oral dosage forms.³  Nearly 75% of active pharmaceutical ingredients (APIs) are bitter due to their chemical structure. Many APIs are derived from plants that humans perceive as bitter.^2,4  This bitterness impacts the palatability of oral liquid formulations.⁵  Infants and younger children are often unable to take drug dosage forms designed to prevent taste perception of the API, for example, tablets and capsules. As such, manufacturers of liquid formulations often struggle to mask the API.⁶  Prior to this study, the authors created the Ew MedsTM List. A comprehensive search of publications since 1980 that contained scored medication taste perception yielded 20 medications that met the scoring criteria to be considered “Ew Meds”.⁷ 

The known link between palatability and medication adherence leaves children at higher risk of non-adherence and impacts both caregivers’ and prescribers’ ability to care for these patients appropriately.^8–11  The impact of medication taste on adherence highlights the need for taste masking strategies to increase palatability for younger patients. One of the most important factors in taste masking is avoiding altering a medication’s therapeutic effectiveness. Methods such as mixing in food or drinks can alter the pharmacokinetic properties of medications.^12–15  The European Medicine Agency found that children prefer taking the smallest volume of a bad tasting liquid medication unless a more diluted preparation allows for better taste masking.¹⁶  In practice, various techniques are used to mask the taste of liquid medications, including numbing the tongue with ice and eating chocolate syrup after a bitter-tasting medication. However, there is no evidence that these recommended techniques are effective. Consequently, research is needed to determine optimal taste masking techniques for liquid medications to make them palatable for children.

Within pediatric medicine, research has focused on how to mask bad tasting medications, yet a significant gap remains in understanding how well health care providers, including pediatricians, physician assistants and pediatric nurse practitioners, are educated in recognizing these bad tasting medications. One study at the University of Maryland documented that students in their last professional year of school from dentistry, medicine, nursing, and pharmacy were able to correctly identify only 30% of bad tasting medications from a list.¹⁷  Currently, there is no literature evaluating health care providers’ ability to identify bad tasting medications.

The primary objective of this study was to determine pediatric prescribers’ knowledge and confidence in identifying bad tasting liquid medications. The secondary objective examined the techniques prescribers use in practice to mask the taste of liquid medications and whether any of the masking techniques recommended by prescribers were reported to be effective in children.

This study was a qualitative online survey that asked prescribers questions about medication tastes and taste masking practices and was administered using Qualtrics (Qualtrics, Provo, UT). Participants included a national convenience sample of health care providers (physicians, physician assistants, and nurse practitioners) who prescribe oral liquid medications. Prescribers were excluded if they did not care for children less than 12 years of age.

The survey consisted of 17 questions total (see Supplemental Table): 4 demographic questions (response required); 6 about their patient population, practice site, and prescribing habits (response required); 1 on confidence identifying bad tasting medication (response required); 1 on knowledge of bad tasting medications (response required); 4 on taste-masking (response optional); and 1 on potential taste tools (response optional, included for future quality improvement project). For the knowledge of bad tasting medications, providers were given a list of 22 bad and better tasting medications in alphabetical order by generic name and asked to identify those with evidence of bad taste (Table 1). The list of medications was established using evidence generated from the Ew Meds^TM List. Providers were asked to rate their confidence in identifying bad tasting medications. Additionally, they were asked to share medication taste masking practices recommended to their patients and if those recommendations worked; if medication prescriptions had to be changed due to bad taste; and how often education is provided to patients about taste masking. Providers who completed the survey were given access to the online educational Ew Meds List infographic about bad tasting medications and taste masking practices (https://www.pediatricmeds.com/home/provider-resources). The survey was piloted by 5 pharmacists outside the study team to check for clarity of survey questions.

Health care providers were invited to participate in the study between January and October 2022. Survey links were sent to National Academies of Practice and the American Academy of Pediatrics members via paid third parties who facilitated dissemination as dictated by the organizations’ websites. Advertisements, including a QR code linking to the survey, were shared through social media sites (e.g., LinkedIn, Facebook, Twitter), local health system mailing lists, and at a University of Maryland-sponsored booth during a national family medicine physicians’ meeting expo.

Descriptive statistics were used to assess survey responses. Spearman correlation was used for the relationship tests of ordinal data.

Seventy-five prescribers completed the survey. The majority identified as white (55/75, 73%), between the ages of 35 to 54 (46/75, 61%), female (62/75, 83%), located in the Northeast (35/75, 47%), and practicing at a health-system clinic (30/75, 40%). Years in practice were evenly distributed among 0 to 5 years (22/75, 29%), 6 to 10 years (19/75, 25%), 11 to 20 years (18/75, 24%), or more than 20 years (16/75, 21%). Children less than 12 years of age comprise more than a third of the total patients for 85% of the prescribers (Table 2).

When asked about their confidence in identifying bad tasting medications, 26/75 (34.7%) of providers felt moderately or extremely confident. On average, prescribers correctly identified 27.9% of bad tasting medications (median score 3.35/12). Eighty percent report prescribing sulfamethoxazole/trimethoprim in the last year; however, only 26/75 (34.7%) correctly identified that medication as a bad tasting medication. The bad tasting medications most often correctly identified included clindamycin (74.4%) and prednisolone (68%). The bad tasting medications correctly identified least often were ritonavir (8%), penicillin VK (9.3%), and cefuroxime (9.3%). The better tasting medications most often incorrectly identified as bad tasting were amoxicillin-clavulanate (36%) and azithromycin (20%; Figure – Better Tasting Medications). There was no correlation between confidence level and correctly identifying bad tasting medications (r_s = 0.263). Also, there was no correlation between years in practice and correctly identifying bad tasting medications (r_s = 0.263).

When asked about how often they educate patients about masking bad tasting medications, 21/71 (29.6%) responded “most of the time” or “always” and 9/71 (12.7%) responded “never”. There was no correlation between how often prescribers educate and correctly identify bad tasting medications (r_s = 0.319); however, there was a strong relationship between level of confidence and frequency of educating patients on masking bad tasting medications (r_s = 0.674). The most common taste masking recommendations were mixing the medication in food or drink (55/58, 95%), having the pharmacy flavor the medication (51/55, 93%), giving a drink right after medication administration (44/49, 90%), giving chocolate syrup right after the medication (32/41, 78%), and using an oral syringe to push the medication to the side or back of the mouth (54/71, 76%). Despite a majority of prescribers recommending these aforementioned masking techniques, less than half reported whether the technique worked or didn’t work. For all the techniques, comparable amounts of prescribers reported masking techniques as both effective and ineffective (Table 3).

More than half of prescribers, 49/71 (57.7%) reported having to change a medication prescription because of bad taste. Forty-one prescribers cited 49 medication prescriptions that had to be changed. Of these 49 medications, there were 17 different prescription medications listed with the most common medications being: prednisolone/prednisone (13/49, 27%), clindamycin (12/49, 25%), and amoxicillin/clavulanic acid (8/49, 16%). Other medications noted to have been changed included acetaminophen (1/49, 2%), amoxicillin (1/49, 2%), clarithromycin (1/49, 2%), cefdinir (1/49, 2%), erythromycin (1/49, 2%), ferrous sulfate (2/49, 4.1%), levetiracetam (1/49, 2%), metformin (1/49, 2%), metronidazole (1/49, 2%), oseltamivir (2/49, 4.1%), poly-vi-sol (1/49, 2%), a proton-pump inhibitor (1/49, 2%), ranitidine (1/49, 2%), and sulfamethoxazole-trimethoprim (1/49, 2%).

This is the first study of its kind examining pediatric prescriber’s knowledge of bad tasting medications in the United States. This study assessed pediatric prescribers’ knowledge and attitudes about the taste of liquid medications and techniques prescribers use in practice to mask the taste of liquid medications. The observed lack of knowledge in identifying bad tasting medications among pediatric prescribers reflects a significant gap in their education which is consistent with a similar study at the University of Maryland looking at health care students’ knowledge. This previous study reported that students across various health care professions had limited ability to identify bad tasting medications. Medical students identified they did not receive any education on medication taste familiarity in their required curriculum.¹⁷  Although the previous study was at a single institution and included students in their last year of school, our study was conducted across the country with practicing pediatric providers with almost a quarter having over 20 years of experience. Therefore, the lack of knowledge about bad tasting medications seems to be a widespread national problem. Pediatric providers need an early introduction to this material while in school and continuing education to reinforce and highlight the clinical consequences of poor palatability.

The study highlights a lack of confidence among pediatric prescribers in identifying bad tasting medications. We hypothesized that prescribers with lower confidence would be less likely to correctly identify bad tasting medication, but this relationship did not exist. It is less surprising that prescribers with higher levels of confidence reported educating their patients on taste masking more frequently. The ability of prescribers to recognize different tasting medications reflects the need for targeted educational interventions to enhance their awareness of this critical topic which could then be shared with their patients.

Almost all prescribers recommended mixing the medications in food. The practice of mixing medications in food can potentially prevent the patient from receiving the full dose and could alter the pharmacokinetic effects of medications.¹⁶  Commercially available flavoring systems are preferred over recommending caregivers to add or change flavoring agents because the use of untested flavoring agents might have a variable effect on drug absorption, stability and patient’s overuse of medication. Altering the flavor can also affect the medication’s physical properties, such as viscosity or density.¹⁸  Additionally, a high number of respondents in our study reported changing medications due to bad taste suggesting an existing link between bad tasting medications and non-adherence in pediatric patients. A similar relationship between medication refusal and perceived bad taste has previously been demonstrated in three studies.^8–10  Needing to change medication therapy due to taste results in increased cost to both the health care system and direct cost to the family.^19,20  Additionally, clinical implications of care delays or therapy interruptions lead to poor adherence and could result in poor health outcomes.^21,22  These results stress the urgency of addressing taste-related implications in pediatric medication management.

In all fairness to prescribers, there is a lack of evidence for the effectiveness of commonly used taste masking practices such as chocolate syrup chasers, using an oral syringe to miss the taste buds, and giving a drink after the medication dose. In the Ew Meds^TM List, only the following medications have evidenced-based taste masking techniques: cefuroxime axetil with chocolate syrup chaser; didanosine, efavirenz, indinavir, nevirapine, stavudine and zidovudine with FLAVORx (raspberry mixed with vanilla and mango), ritonavir mixed with chocolate milk, efavirenz mixed with grape jelly, and ibuprofen and lansoprazole added strawberry-flavored syrup.⁷  Our study tried to examine if any of the masking techniques recommended by prescribers were reported to be effective in children. In general, the taste masking techniques reported by pediatric prescribers had mixed effectiveness, indicating a need for well-designed studies to know what truly works. Establishing effective taste masking techniques will help health care providers make informed decisions about prescribing medications that are palatable for pediatric patients and ultimately impact patient health outcomes.

This study has some limitations. The small sample size may limit the generalizability of the study and may not adequately represent the knowledge and confidence of all pediatric prescribers despite having a nationally representative sample. The limited number of responses to questions about taste masking technique efficacy may have been impacted by provider recall bias.

Based on prescribers’ limited confidence and knowledge, education about bad tasting liquid medications and appropriate taste masking should be readily available, including the dangers of altering medication efficacy when mixing in food and drink. More research is needed to develop evidence-based and effective taste masking practices in children until such time that dosage forms can be developed that will eliminate the need for taste masking.​

API

active pharmaceutical ingredient

Dafne Espinal Peña was a student pharmacist at the time of this publication's acceptance. She has since received her PharmD. The results of this study were presented at the American Pharmacists Association Annual Meeting in March 2023.