SPECIAL ARTICLE

JPPT | 2025 KIDs List

Pediatric Pharmacy Association 2025 KIDs List of Key

Potentially Inappropriate Drugs in Pediatrics
Christopher McPherson, PharmD; Rachel S. Meyers, PharmD; Jennifer Thackray, PharmD; Danielle L. Stutzman, PharmD;
Kimberly P. Mills, PharmD; Sana J. Said, PharmD; Karisma Patel, PharmD; Robert C. Hellinga, PharmD;
Amy L. Potts, PharmD, MMHC; Lisa Lubsch, PharmD; Kelly L. Matson, PharmD; and David S. Hoff, PharmD

OBJECTIVE The objective was to update the KIDs List, a list of drugs and excipients that are potentially
inappropriate for use in pediatric patients, accounting for emerging pharmacologic agents and published
evidence.
METHODS A panel of 12 pediatric pharmacists from the Pediatric Pharmacy Association (PPA) evaluated
primary, secondary, and tertiary literature; FDA Pediatric Safety Communications; the UpToDate Lexidrug
database; and product information for drugs that may be considered potentially inappropriate for use in
pediatric patients. A PubMed search identified new publications from October 1, 2017, to November 1, 2023.

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All agents included in the previous publication and those anecdotally identified as candidates for the list by
the authors or PPA members were evaluated. Evidence was reviewed by all authors. The draft list under-
went a 30-day public comment period prior to being finalized.
RESULTS A PubMed search yielded 917 unique titles of which 17 were deemed relevant for full review.
Sixty-seven drugs and/or drug classes and 10 excipients from the original publication were also reviewed.
Author and PPA member recommendations highlighted an additional 25 drugs or drug classes. The UpTo-
Date Lexidrug database extraction yielded 1470 drugs, which were filtered to 145 agents for author review.
After critical analysis and reorganization, the second edition of the KIDs List contains 39 drugs and/or drug
classes and 10 excipients.
CONCLUSIONS This article updates the initial list of drugs and excipients that are potentially inappropriate
for prescribing in all or a select subgroup of pediatric patients. The second edition should stimulate novel
research to inform future updates.
ABBREVIATIONS AAP, American Academy of Pediatrics; ADR, adverse drug reaction; BPCA, Best Pharma-
ceuticals for Children Act; ED, emergency department; FDA, US Food and Drug Administration; MeSH,
­Medical Subject Headings; NSAIDs, nonsteroidal anti-inflammatory drugs; PPA, Pediatric Pharmacy
­Association; PREA, Pediatric Research Equity Act; WHO, World Health Organization
KEYWORDS adverse drug event; adverse drug reaction; excipients; medications; pediatrics; potentially
­inappropriate medication list
J Pediatr Pharmacol Ther 2025;00(0):1–18

DOI: 10.5863/JPPT-25-00061

Introduction account for up to 4% of pediatric hospitalizations and

Adverse drug reactions (ADRs) represent a significant occur in up to 18% of hospitalized pediatric patients.4–6
health care burden. Every year, 6 of every 1000 adults will While some ADRs are iatrogenic and unpredictable,
visit the emergency department (ED) for an ADR.1 Nearly others are unintended but expected based on the phar-
40% of these visits prompt hospitalization, a setting in macology of the drug. Regardless of etiology, these ADRs
which serious ADRs occur in 6.7% of patients with a fatal- are most likely preventable. In addition to harm, prevent-
ity rate of 0.32%, representing a top-10 cause of death.2 able ADRs add unnecessary burden to the patient and
Specific subpopulations experience higher risk, including caregivers as well as additional cost to the health care
those at the extremes of the age spectrum.3 Serious ADRs system. It has been documented that up to half of ADRs
in hospitalized pediatric patients are preventable.7
Multiple underlying reasons for higher rates of ADRs
Submitted May 15 2025; Accepted May 15 2025; in the pediatric population exist, including frequent
Published online July 15 2025 off-label drug usage, the need for individualized dose

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PPA 2025 KIDs List McPherson, C et al

calculations, and age-related differences in drug dispo- with a high risk for ADRs at pediatric hospitals and
sition and effect. Currently more than 4400 medications health systems caring for pediatric patients.19–23 Ad-
are available in the United States, with approximately ditionally, the KIDs List has catalyzed vital research in
50 new medications being approved each year by the pediatric population, supporting dialogue among
the US Food and Drug Administration (FDA). 8 The interprofessional practitioners, pediatric institutions,
Best Pharmaceuticals for Children Act (BPCA) and the and the public.24–26 To continue this work, the Pedi-
Pediatric Research Equity Act (PREA) have stimulated atric Pharmacy Association (PPA) commissioned an
significant research on medications in children.9 How- expanded group of pediatric pharmacists to evaluate
ever, 64% of new drugs and biologics lack pediatric pre- the medical literature and update the list of drugs that
scribing information within 5 years of FDA approval.10 should be “avoided” or “used with caution” in all or a
Additionally, indications for 40% of ordered medications subset of the pediatric population.
in hospitalized pediatric patients and more than 50%
in neonates remain off-label.11,12 In the outpatient set- Materials and Methods
ting, approximately 20% of pediatric and more than Panel Selection and Composition. The PPA Board
80% of neonatal visits result in 1 or more off-label drug of Directors solicited revision of the first edition of
prescriptions.13 Although lack of FDA labeling does the KIDs List on June 20, 2023. All panel members
not preclude high-quality, evidence-guided therapy, completed a conflict-of-interest disclosure form at the

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the high frequency of off-label medication use in the beginning of the process and reaffirmed disclosure at
pediatric population is mainly due to the use of older, each panel meeting. No panel member had a conflict
generic drugs, which did not benefit from the research of interest that precluded participation.
requirements of PREA and BPCA. The use of many of Literature Search and Review. Electronic databas-
these older drugs may rely on data from case reports, es, published communications, FDA product labeling,
anecdotal observational experience, and historical clinical practice guidelines, panel member expertise,
dogma to inform prescribing patterns in pediatrics. and external reviewers were used to ensure consid-
An important contributing factor leading to an in- eration of novel candidate drugs and excipients. The
creased rate of ADRs in the pediatric population is process is described in Figure 1. Published sources
the rapid ontogeny of organs involved in the absorp- were collected, screened, and assessed for eligibility,
tion, metabolism, and elimination of systemic drugs.14 using the PRISMA strategy.27
Specific risk points include a thinner stratum corneum PubMed. A PubMed search was conducted to
in neonates, enhancing percutaneous absorption of identify articles published after data screening for the
topically administered drugs; immature hepatic enzyme first KIDs List edition, using a date range of October
systems in infancy, decreasing metabolism; and incom- 1, 2017, to November 1, 2023. The search terms were
plete renal glomeruli and tubules for the first year after adverse drug events and adverse drug reactions as
birth, affecting elimination of drugs and/or metabolites. Medical Subject Headings (MeSH) with filters of “Eng-
The complexity and timing of the development of each lish,” “Child: birth-18 years,” “Humans,” and “Case
of these organ systems have the potential to increase reports,” “Observational study,” or “Clinical trial.” Ab-
ADRs from drugs that have a comparatively lower risk stracts were reviewed by 2 panel members. If one of
of toxicity in adults. those individuals concluded that the drug or excipient
In the early 1990s, geriatrician Mark Beers led a Delphi warranted further consideration, the full text was re-
study to formulate a list of drugs that are potentially inap- viewed based on area of subspecialty pediatric exper-
propriate for use in patients 65 years and older residing tise and presented to the full panel for consideration.
in nursing homes.15 The “Beers Criteria” have since been UpToDate Lexidrug. An UpToDate Lexidrug staff
updated 6 times, expanded to include all adults older member searched the Lexi-Drugs and Pediatric and
than 65 years, endorsed by the American Geriatrics Neonatal Lexi-Drugs databases on February 6, 2024.
Society, and integrated into a trademarked software The fields “Warnings: Additional Pediatric Consider-
application.16 The Beers Criteria represent a standard ations,” “Adverse Drug Reaction (Significant) Consider-
of care that has improved safe prescribing and use of ations,” “Warnings/Precautions,” “Special Alerts List,” and
drugs in older adults.17 A comparable evidence-based “Alert: U.S. Boxed Warnings” were searched by using the
list of drugs was published in 2020 that sought to bring following terms: “children” OR “pediatric” OR “neonate”
a similar focus to unintended and preventable ADRs OR “infant” OR “child” OR “adolescent.” Two panel mem-
in the pediatric population, namely the Key Potentially bers narrowed the list as described in Supplemental Ma-
Inappropriate Drugs in Pediatrics, or “KIDs List.”18 terial 1. The list of potential candidate monographs was
The KIDs List has improved medication safety in pedi- reviewed by the entire panel with literature searches
atric patients through dissemination of evidence-based conducted at the request of any member. Each literature
information, incorporation into information systems, and search was conducted by a single panel member, based
quality improvement initiatives. Clinician-scientists have on area of subspecialty pediatric expertise and present-
used the KIDs List to identify medications associated ed to the full panel for consideration.

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McPherson, C et al PPA 2025 KIDs List

Figure 1. Methods for development of the updated KIDs list.

Updated list of drugs developed:

Systematic literature review, Panel discussions to debate
Literature review of drugs from
FDA Pediatric Safety inclusion and rate the strength
the first edition and the updated
Communications, UpToDate of the recommendations and the
list
Lexidrug database, panel and quality of the evidence
external opinion

Panel discussions and Open comment period from the

KIDs List finalized presentation at PPA annual membership of the Pediatric
meeting; expert review from Pharmacy Association (PPA)
outside sources

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FDA, US Food and Drug Administration; PPA, Pediatric Pharmacy Association.

FDA Communications. FDA Pediatric Safety Com- children than adults and a safer alternative is avail-
munications (https://www.fda.gov/science-research/ able.” This list is meant to serve as a clinical tool and
pediatrics/fda-pediatric-safety-communications) were is not meant to replace clinical judgment or be used
searched by 1 panel member. Communications re- in a punitive manner. Needs of an individual patient,
leased between January 2019 and March 2024 were disease(s) management, or unique situations may
reviewed for relevancy for inclusion in the KIDs List. outweigh the recommendations found in this list. The
Anecdotal Observation. Panel members sug- choice of appropriate medications for pediatric pa-
gested drugs and excipients that were thought to be tients should be made by an interprofessional health
potentially harmful in pediatric patients. Additionally, care team, should include individualized dosing and
the original panel members compiled emails from col- appropriate monitoring, and should consider the val-
leagues regarding exclusions from the first edition. ues and preferences of the child and caregivers.
A PubMed search was conducted on each drug. A Recommendation (Avoid Versus Caution). Two
summary of available evidence was prepared by 2 recommendations were used: avoid and caution.
panelists chosen on the basis of area of subspecialty Avoid was used when the authors deemed that evi-
pediatric expertise. Summaries were reviewed by the dence of clinical benefit did not outweigh the poten-
full panel. tial adverse effect based on any of the following: the
First-Edition Drugs and Excipients. A PubMed severity of the adverse effect, the quality of evidence
search on each drug was conducted and a summary supporting clinical utility, and/or the presence of alter-
of available evidence was prepared by 2 panelists native therapies. Caution was used to describe drugs
chosen on the basis of area of subspecialty pediatric in which benefit in specific clinical scenarios may war-
expertise. Summaries were reviewed by the full panel. rant use despite evidence demonstrating a higher risk
External Review. The draft tables were submitted of adverse effect(s) in children than adults.
to the members of PPA for review via an electronic Strength of Recommendation (Strong or Weak). This
communication. Comments were accepted from Feb- assessment reflected a classification by the panel
ruary 7, 2025, through March 7, 2025. The panel re- describing the seriousness of an ADR, the extent to
searched all comments for discussion, consensus, which the clinician can confidently conclude that the
and revision to the manuscript, if appropriate. undesirable effect(s) of the intervention outweighs
Operational Definitions. ADR. The panel adopted the desirable effect(s). A “strong” recommendation is
the World Health Organization (WHO) description of predicated on the belief that most informed clinicians
an ADR as “a response to a medicine which is noxious would choose the recommended course of action. A
and unintended, and which occurs at doses normally strong recommendation implies that a clinician pre-
used in man.”28 sented with information about a specific ADR would
Potentially Inappropriate Medication. Potentially choose to avoid or use the drug cautiously in lieu of
inappropriate medications were defined as “medica- assuming the risk of the ADR. A strong recommenda-
tions or medication classes that should generally be tion allows clinicians to have confidence in their in-
avoided in persons 18 years or younger because they teractions with patients and to structure discussions
pose a higher risk of one or more significant ADRs for accordingly. Conversely, a weak ­recommendation is

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PPA 2025 KIDs List McPherson, C et al

consistent with significant variability in the clinician’s professionals directly involved in the patient’s care.
decision when presented with information about a Treatment with drugs on this list may be warranted
specific ADR. The clinician must carefully examine depending on the clinical situation. The KIDs List is
specific treatment decisions in this context because not a substitute for clinical judgment. There may be
these decisions may vary according to the caregivers’ specific populations or diseases for which treatment
and patients’ values and preferences. with any of these drugs is warranted.
Quality of Evidence. The quality of evidence re-
flects the aggregate of published information. The Results
quality of evidence definitions used for the “KIDs Between September 2023 and October 2024, the
List: Second Edition” were based on those from the panel held monthly virtual meetings; live meetings oc-
GRADE recommendations and the Beers Criteria.29,30 curred on May 2 and May 3, 2024. A summary of the
An assessment of “high” quality indicates that further systematic review and identification of included drugs
published information or research is very unlikely to and excipients is outlined in Figure 2. The initial PubMed
alter our confidence in the recommendation or esti- search yielded 917 unique titles. Panel members identi-
mate of ADR effect. “Moderate” quality suggests that fied 17 articles for full-text review. A search of all 4149
further research may have a significant impact on our drugs included in the 2 UpToDate Lexidrug databases
confidence because it may influence or change the yielded 1470 unique drugs of which 145 were included

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evidence regarding a recommendation. “Low” quality for consideration by the full panel (Supplemental Mate-
implies that further published information or research rial 1). No relevant FDA Pediatric Safety Communications
is likely to affect our confidence in the estimate of ef- from the period since the original KIDs List were identi-
fect and may change the conclusion. The KIDs List fied. Twenty-five drugs or drug classes were evaluated
panel elected to use a “very low” classification of evi- on the basis of anecdotal observation. Sixty-seven
dence given the paucity of high-quality data on ADRs drugs and/or drug classes and 10 excipients were evalu-
in pediatrics. “Very low” quality implies that any esti- ated on the basis of their inclusion in the first edition.
mate of effect is very uncertain. The final KIDs List contains 39 drugs or drug classes
Scope. This list should serve as a useful resource (Table 1). There was sufficient evidence to classify
for clinicians and institutions caring for pediatric pa- 18 drugs/drug classes as “avoid” in all or a subgroup of
tients and provide a basis for allocation of resources pediatric patients; 19 are classified as “use with caution”;
and additional research to improve drug safety in the 2 drugs were included owing to dosing or concentration
pediatric population. During the review process, only limits specific to pediatric patients. Sixty-seven percent
those drugs approved for use in the United States, of drugs classified as “avoid” had a combination of
regardless of FDA-labeled age, were considered. strength of recommendation plus quality of evidence as
Hence, application of this list for pediatric patients in either “strong” and “high” or “strong” and “moderate.”
countries other than the United States may be incom- Drugs removed from or added to the KIDs List are
plete. It should be noted that some drugs included on outlined in Supplemental Material 2. Among the 5 drugs
this list are also on the WHO Model List of Essential removed from the list, 3 were removed owing to lack
Medicines for Children.31 Acceptable therapeutic alter- of commercial availability in the United States, while 2
natives readily available in the United States (for the were removed owing to emerging evidence. All drugs
same indication) played a role in the expert panel’s added to the KIDs List occurred in the setting of low
determination to include a drug in the KIDs List. The or very low quality of evidence, primarily consisting of
KIDs List is not intended to supersede recommenda- product labeling.
tions for drugs found in the WHO Model List of Essen- Ten excipients were identified (Table 2). All 4 “avoid”
tial Medicines for Children. Use of these drugs outside recommendations were conditional, with 3 as dose
the United States for certain clinical conditions may be limitations and 1 contingent upon newborn genetic
warranted. screening. Moderate- or high-quality evidence drove
Intent and Audience. The intent of the KIDs List is most recommendations (70%).
to improve the safety of medication use in pediatric
patients, educate clinicians, and serve as a quality im- Discussion
provement tool. The primary target audience of this Lack of an updated evidence-based reference
publication is health care professionals caring for pa- prompted the first edition of the KIDs List.18 The cur-
tients 18 years of age or younger regardless of setting. rent publication is an update of the list of potentially
The KIDs List is intended to be an evidence-based inappropriate drugs in pediatrics, reflecting the most
guide to supplement clinical decision-making. The current information. Refining the initial process and
recommendations do not suggest absolute contrain- expanding the author panel led to a carefully compiled
dication of any drug in any pediatric patient. As in all list of 39 drugs or drug classes and 10 excipients war-
medical cases, the entire clinical picture of the patient ranting avoidance or caution in some or all pediatric
must be assessed and evaluated by the health care patients. Notably, these figures represent relative

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McPherson, C et al PPA 2025 KIDs List

Figure 2. Results of literature search, expert opinions, FDA Pediatric Safety Commu-
nications, and UpToDate Lexidrug database search.

Abstracts determined to be
PubMed Initial Literature
potentially relevant and the
Search:
full article was reviewed:
917 unique titles
17

Compounds/classes for which

First edition:
a literature search was
67 drugs and/or drug classes conducted:
and 10 excipients Included in the updated KIDs
77
List:
39 drugs or drug classes
Compounds/classes for which and 10 excipients
Internal and external a literature search was
anecdotal observation: 25 conducted:
drugs and/or drug classes
25

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UpToDate Lexidrug Drugs determined to be
database search for potential potentially relevant:
pediatric safety concerns:
4149 drugs 145

FDA, US Food and Drug Administration.

equilibrium with the first edition, with specific attention or less) of susceptible infections, such as rickettsial
paid to highlighting class effects, when supported by disease, Lyme disease, vibriosis, and anthrax, where
evidence. Several debates occurred during roughly 20 equally effective alternatives are not available.34
hours of panel meetings to produce simple, concise, Antipsychotics. Pediatric mental health has
consensus recommendations, ranging from ancient strained the global health system with many clinical
debates about tetracyclines and teeth to emerging considerations informing the use of antipsychotics in
controversies regarding the safety and efficacy of youth.35 Youth are at an increased risk for acute dys-
neuropsychiatric medications in children. We have tonic reactions and hyperprolactinemia with the use
highlighted the rationale behind some of the commit- of first-generation antipsychotics (e.g., haloperidol)
tee’s recommendations below. given sensitivity to their potent D2 blockade within
Tetracyclines. The impact of tetracycline on teeth the nigrostriatal and tuberoinfundibular dopamine
has been acknowledged for well over 60 years.32 pathways.36–40 While first-generation antipsychotics
Emerging evidence since the first publication of the are sometimes used in clinical practice, particularly
KIDs List allowed a closer examination of the tetra- for the management of acute agitation or aggres-
cycline antibiotics as a class. A strong recommenda- sion, the panel agreed that alternative agents (e.g.,
tion is now being made to caution against the use of olanzapine) are available with a reduced risk for ad-
several additional tetracyclines owing to tooth discol- verse effects. This recommendation is in alignment
oration. It is likely that additional research will further with updated pediatric treatment guidelines and lit-
inform the strength of this recommendation. While erature.41–43
tetracyclines are known to bind to calcium and are in- While second-generation antipsychotics are a rea-
corporated into teeth and bone to some extent with sonable alternative to first-generation antipsychotics in
bone remodeling in persons of all ages, tooth discol- some instances, the panel also considered their many
oration is most prominent when tetracyclines are ad- pediatric-specific adverse effects. Metabolic risk is of
ministered before mineralization of the succedaneous critical importance in this age group, considering that
teeth is completed by 8 years of age, excluding third youth are at an increased risk for developing weight
molars.33 Although tetracyclines should be avoided in gain, metabolic syndrome, dyslipidemia, and/or type 2
children younger than 8 years, their use may be nec- diabetes with second-generation antipsychotic use.44
essary in some children. Of note, while doxycycline The panel acknowledged that their long-term use can-
has a similar molecular structure to tetracycline, in not be avoided in youth with a severe mental illness (i.e.,
vivo reports of tooth discoloration, enamel hypopla- schizophrenia spectrum, bipolar mood disorders), but
sia, and bone growth retardation are largely lacking. there are many evidence-based medication alternatives
Therefore, its use in young children is recommend- for other indications (e.g., stimulants for impulsive ag-
ed as first-line for the short-term treatment (21 days gression in the setting of attention-deficit/­hyperactivity

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PPA 2025 KIDs List McPherson, C et al

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Angiotensin receptor Renal tubular Caution in younger Weak Very low

blockers66–69 dysgenesis than 1 mo
Azilsartan
Candesartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan

Atazanavir70,71 Kernicterus Caution in younger Weak Very low

than 3 mo unless
pharmacogenetic

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testing is used

Camphor, topical72–74 Seizures Caution in 18 yr of Weak Very low

age and younger

Carbinoxamine75 Death Avoid in younger Strong Low

than 2 yr

Ceftriaxone76–79 Kernicterus Caution in younger Weak Very low

than 3 wk except
for one-time doses
for gonococcal
treatment

Chloramphenicol80 Gray baby syndrome Avoid in younger Strong High

than 1 mo
unless serum
concentration
monitoring is used

Chlorhexidine, Chemical burn Caution with Weak Low

topical81–83 concentrations
>0.5% in less than
7 days old and less
than 34 weeks’
gestation
Caution with
concentrations
>2% in younger
than 1 mo

Corticosteroids, topical Cushing syndrome, Avoid in younger Strong Low

(medium, high, and adrenal suppression than 2 yr for diaper
very high potency)84 dermatitis

Darunavir85 Seizures, death Avoid in younger Strong Very low

than 3 yr or ≤10 kg

Dicloxacillin86 Kernicterus Caution in younger Weak Very low

than 1 mo

Dicyclomine87,88 Apnea Avoid in younger Strong Low

than 6 mo

Difluprednate89,90 Increased intraocular Caution in 18 yr of Weak Low

pressure age and younger

(Table cont. on page 7)

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McPherson, C et al PPA 2025 KIDs List

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition (cont.)
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Diphenoxylate and Respiratory failure, Avoid in younger Strong Moderate

atropine91,92 death than 6 yr

Dopamine antagonists

First-generation Acute dystonic Avoid in 18 yr of Strong High

antipsychotics36–40 reactions (e.g., age and younger
Chlorpromazine oculogyric crisis,
Droperidol torticollis)
Fluphenazine
Haloperidol Hyperprolactinemia Weak High
Loxapine
Perphenazine
Pimozide

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Thiothixene
Thioridazine
Trifluoperazine

Prochlorperazine93–95 Acute dystonic Avoid in younger Strong Moderate

reactions (e.g., than 2 yr
oculogyric crisis, Caution in 2–18
torticollis) years of age

Second-generation Withdrawal Avoid rapid Strong High

antipsychotics36,37,44,46,47 emergent dystonia/ discontinuation in
Aripiprazole dyskinesia 18 yr of age and
Asenapine younger
Brexpiprazole
Cariprazine Type 2 diabetes, Avoid use of Strong High
Clozapine weight gain, olanzapine for a
Iloperidone dyslipidemia, duration of >12 wk
Lurasidone and/or metabolic in 18 yr of age and
Lumateperone syndrome (risk younger
Olanzapine greater for clozapine Caution in 18 yr of
Paliperidone ≥ olanzapine age and younger
Quetiapine > quetiapine
Risperidone > risperidone,
Ziprasidone paliperidone,
iloperidone >
asenapine >
aripiprazole,
brexpiprazole
> lurasidone,
cariprazine >
ziprasidone,
lumateperone)

Hyperprolactinemia Caution in 18 yr of Strong High

(risk greater for age and younger
paliperidone >
risperidone >
olanzapine)

Metoclopramide93,96,97 Acute dystonic Avoid in younger Strong High

reactions (e.g., than 1 yr
oculogyric crisis, Caution in 1–18 yr
torticollis) of age

(Table cont. on page 8)

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PPA 2025 KIDs List McPherson, C et al

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition (cont.)
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Promethazine98,99 Respiratory failure, Avoid in younger Strong Moderate

death than 2 yr
Acute dystonic Caution in 2–18 yr
reactions (e.g., of age
oculogyric crisis,
torticollis)

Trimethobenzamide100,101 Acute dystonic Avoid in 18 yr of Strong Low

reactions (e.g., age and younger
oculogyric crisis,
torticollis)

Ester local anesthetics

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Benzocaine, topical102 Methemoglobinemia Avoid oral Strong High
application in
younger than 2 yr

Lidocaine viscous, Central nervous Avoid oral Strong High

topical103,104 system depression, application in
seizures, arrhythmia, younger than 2 yr
death

Gentamicin ophthalmic Severe ocular Avoid in younger Strong High

ointment105–107 reactions than 1 mo

Guanylate cyclase-C
agonists

Linaclotide108 Death from Caution in younger Weak Very low

dehydration than 2 yr

Plecanatide109 Death from Caution in 18 yr of Weak Very low

dehydration age and younger

Lamotrigine37,110,111 Skin rashes ranging Caution in 18 yr of Strong High

in severity from age and younger;
benign to life- slow dose titration
threatening required

Loperamide112 Ileus, lethargy Avoid in younger Strong High

than 3 yr for acute
infectious diarrhea

Macrolides34,113–115 Hypertrophic pyloric Avoid in younger Strong High

Azithromycin stenosis (risk greater than 1 mo except
Erythromycin for erythromycin > for Bordetella
azithromycin) pertussis
(azithromycin)
or Chlamydia
trachomatis
pneumonia
(azithromycin and
erythromycin).
Caution in younger
than 1 mo for
Ureaplasma
(azithromycin).

(Table cont. on page 9)

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McPherson, C et al PPA 2025 KIDs List

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition (cont.)
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Malathion, topical116,117 Organophosphate Caution in younger Weak Very low

poisoning than 2 yr

Midazolam118,119 Severe Caution in patients Weak Low

intraventricular weighing less than
hemorrhage, 1500 g
periventricular
leukomalacia, or
death

Mineral oil120 Lipid pneumonitis Avoid in younger Strong Low

than 1 yr

Mirabegron121 Increased blood Caution in younger Weak Very low

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pressure than 3 yr

Molnupiravir122 Bone and cartilage Caution in 18 yr of Weak Very low

toxicity age and younger

Montelukast123 Sleep disturbances Caution in 18 yr of Weak Very low

age and younger

Naloxone124 Seizures Avoid in neonates Strong High

for postpartum
resuscitation

Nitrofurantoin125 Hemolytic anemia Avoid in younger Weak Very low

than 1 mo

Opioids

Codeine126–130 Respiratory failure, Avoid in younger Strong High

death than 12 yr
Avoid in 12–18
yr of age after
surgery to remove
tonsils and/or
adenoids
Caution in 12–18 yr
of age
Recommend
pharmacogenetic
testing

Meperidine131,132 Acute neurotoxicity Avoid in younger Strong High

(agitation, than 1 mo
myoclonus, Caution in 18 yr of
hyperreflexia, age and younger
tremors, delirium,
seizures)

Opium tincture133 Respiratory failure Avoid in younger Weak Low

than 1 mo
Caution in 18 yr of
age and younger

(Table cont. on page 10)

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PPA 2025 KIDs List McPherson, C et al

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition (cont.)
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Tramadol129,130,134 Respiratory failure, Avoid in younger Weak Low

death than 12 yr
Avoid in 12–18
yr of age after
surgery to remove
tonsils and/or
adenoids
Caution in 12–18 yr
of age
Recommend
pharmacogenetic
testing

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Propofol135–137 Propofol-related Avoid doses Strong Moderate
infusion syndrome >4 mg/kg/hr for
greater than 48 hr
in 18 yr of age and
younger

Ribavirin (oral Sudden respiratory Caution in younger Strong Low

inhalation)138 deterioration than 2 yr

Salicylates139,140 Reye syndrome Caution in 18 yr of Weak Very low

Aspirin age and younger
Bismuth Subsalicylate with suspicion
Salicylic Acid (topical) of viral illness
Salsalate (influenza and
varicella)

Sodium phosphate Electrolyte Avoid in younger Strong High

solution enema, abnormalities, than 2 yr
rectal141,142 acute kidney injury,
arrhythmia, death

Sodium polystyrene Colonic perforation Caution in patients Weak Low

sulfonate143,144 weighing less than
1500 g

Sulfonamides145 Kernicterus Caution in younger Weak Very low

Silver sulfadiazine, than 1 mo
topical
Sulfadiazine
Sulfamethoxazole

(Table cont. on page 11)

disorder). While metabolic risk is a class effect, it is generation antipsychotics, based on updated literature
important to acknowledge that olanzapine is the only to support pediatric-specific risk.36,37,44,46,47
agent that has a manufacturer-specific recommenda- Montelukast. An enhanced focus on pediatric men-
tion to avoid its use first-line in youth given its high risk tal health has contributed to novel concerns regarding
for metabolic adverse effects.45 When clinically neces- widely used medications. Montelukast has played a
sary to use a second-generation antipsychotic, agents prominent role in the treatment of asthma and aller-
with a lower metabolic risk should be considered (see gic conditions in children since its approval in 1998.
Table 1 for risk delineation). Withdrawal-emergent In 2020, the FDA released a boxed warning about
dystonia/dyskinesia and hyperprolactinemia were also serious neuropsychiatric adverse effects with monte-
included as important considerations with second- lukast.48 These effects include irritability, aggression,

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McPherson, C et al PPA 2025 KIDs List

Table 1. Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List: Second Edition (cont.)
Drug (Systemic Risk/Rationale Recommendation Strength of Quality of
Administration Unless Recommendation Evidence
Otherwise Noted)

Tetracyclines33,146–150 Tooth discoloration Caution in younger Strong High

Demeclocycline than 8 yr (demeclocycline,
Eravacycline tetracycline)
Minocycline Low
Omadacycline (minocycline,
Sarecycline sarecycline,
Tetracycline tigecycline)
Tigecycline Very low
(eravacycline,
omadacycline)

Enamel hypoplasia Caution in younger Strong High

(tetracycline) than 8 yr

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Retardation Caution in younger Strong Moderate
of skeletal than 1 mo
development
and bone growth
(tetracycline)

Tricyclic Sudden cardiac Avoid in 18 yr of Strong High

antidepressants37,151–153 death age and younger (desipramine)
Desipramine Moderate
Imipramine (imipramine)

Valproic acid and Pancreatitis, fatal Avoid in younger Strong High

derivatives37,154–156 hepatotoxicity than 2 yr
Caution in 2–6 yr

Verapamil157–159 Cardiovascular Caution in younger Weak Low

collapse than 1 yr

anxiety, and mood disorders and have been reported stressed EDs nationwide.53 Nonsteroidal anti-inflam-
in both adults and children with similar frequencies. matory drugs (NSAIDs), acetaminophen, and triptans
Sleep disturbances such as nightmares have been are guideline-recommended treatment options for pe-
shown to occur more commonly in children.49–52 Thus, diatric migraines.54 Emerging literature has suggested
the KIDs List recommendation is to use caution in that the pathophysiology of pediatric migraines may
children 18 years and younger. While the level of evi- differ from that of adults.55 In fact, several studies
dence for this recommendation is very low, clinicians evaluating triptans for the treatment of pediatric mi-
should consider the overall risk of neuropsychiatric graine have not demonstrated greater efficacy than
effects in each individual patient. The KIDs List recom- placebo. The guidance on medication selection in
mendation is based on the evidence of an increase the ED after NSAIDs, acetaminophen, and/or triptan
in sleep disturbances in children. Current evidence failure remains limited; however, the development
does not indicate an overall increased risk in children of a standardized migraine protocol that incorpo-
compared with adults, thus precluding a higher-level rated non-opioid analgesia and a dopamine recep-
warning with montelukast in the KIDs List. Use of mon- tor antagonist was associated with improved patient
telukast in children should be limited to patients who ­outcomes.56 While caution is certainly warranted
will benefit and who can be closely monitored for neu- in pediatric patients, prochlorperazine has demon-
ropsychiatric effects. strated efficacy for the treatment of acute pediatric
Dopamine Receptor Antagonists. Evidence re- migraines; coadministration with diphenhydramine is
garding dopamine receptor antagonists and their a reasonable precaution given the risks of develop-
therapeutic competitors challenged the authors, giv- ing acute dystonic reactions.57,58 Metoclopramide may
en their prevalent adverse effects contrasted against be less effective than prochlorperazine but is a sen-
clear therapeutic niches. An increased prevalence sible alternative if prochlorperazine is not available or
or recognition of migraines in pediatric patients has on ­shortage.59 Further research is necessary to fully

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PPA 2025 KIDs List McPherson, C et al

Table 2. Excipients With Known or Potential Harms When Used in Pediatric Patients
Excipient (Systemic Rationale Recommendation Strength of Quality of
Administration Recommendation Evidence
Unless Otherwise
Specified)

Benzyl alcohol, Gasping Avoid exposure of >99 mg/ Strong High

sodium benzoate, syndrome kg/day in younger than 1 mo
benzoic acid63,160,161 (with the exception of sodium
phenylacetate/sodium benzoate
used for the treatment of urea
cycle disorders)

Ethanol/ethyl CNS depression, Caution in younger than 6 yr: Strong Moderate

alcohol19,63–65 hypoglycemia maximum 0.5% v/v ethanol with
(excluding ethanol clinician supervision
lock) Caution in younger than 12 yr:
maximum of 5% v/v ethanol with

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clinician supervision

Isopropyl alcohol, Chemical burn Caution in patients weighing Weak Low

topical162,163 less than 1500 g

Methylparaben, Kernicterus Caution in younger than 2 mo Weak Very low

propylparaben164

Phenylalanine165 Cognitive and Avoid in 18 yr of age and Strong High

behavioral younger with an unknown
problems phenylketonuria test

Polysorbate Vasculopathic Avoid exposure of ≥72 mg/kg/ Strong High

80166–168 hepatotoxicity day in younger than 1 mo
(E-Ferol Caution exposure of >1.4 mg/day
syndrome) in younger than 1 mo

Propylene glycol169 Lactic acidosis, Avoid >1 mg/kg/day in younger Strong Moderate
CNS depression, than 1 mo
hypoglycemia, Avoid >50 mg/kg/day in 1 mo
hemolysis, of age or older to younger than
seizure 5 yr

CNS, central nervous system

elucidate the optimal abortive regimen for children though published evidence represents a small num-
presenting to the ED for migraines, particularly after ber of infants and ongoing evidence-generation is
failure of guideline-recommended regimens. warranted, human data were given greater weight in
Daptomycin. Important limitations of the KIDs List our analyses than animal or in vitro data. In contrast
highlight gaps in knowledge that continue to affect to daptomycin, many drugs remain on the KIDs List,
the safety of pharmacotherapy in pediatric patients. based on animal or in vitro data in the absence of for-
As an example, daptomycin was included in the first mal human study.
edition of the KIDs List and subsequently removed in Diphenoxylate/Atropine. Panel members were
this iteration. The citation in the first edition was the challenged by clear manufacturer recommendations
package insert, which continues to state, “Daptomy- from product labeling without corresponding support-
cin for Injection is not recommended in pediatric pa- ing data published in peer-reviewed journals. Owing
tients younger than one year of age due to the risk to reported cases of severe respiratory depression
of potential effects on muscular, neuromuscular, and/ and coma, diphenoxylate and atropine should not be
or nervous systems (either peripheral and/or central) administered to patients younger than 2 years. The
observed in neonatal dogs.”60 The recommendation tablet formulation, specifically, is contraindicated in
of caution in the first edition was appropriately classi- children younger than 6 years (and recommended
fied as weak on the basis of very low-quality evidence. for ≥13 years of age). The panel did not change the
Emerging evidence highlights essential and safe use recommendation from the previous edition and rec-
of daptomycin in infants younger than 1 year.61,62 Al- ognizes the challenge for clinicians now that the liquid

12 J Pediatr Pharmacol Ther 2025 Vol. 00 No. 00 www.jppt.org

McPherson, C et al PPA 2025 KIDs List

product has been discontinued from the market. As robust feedback from the community of health care
more safety data emerge in the pediatric population, professionals serving pediatric patients. Knowledge of
the recommendation will be reevaluated. Labeled pediatric pharmacology has expanded at an encourag-
dosing and warnings will be scrutinized for inclusion ing pace to inform the second edition of the KIDs List.
and exclusion. However, significant gaps in knowledge still exist and
Excipients – Ethanol. Excipients represent a unique justify the promotion of both prospective and retro-
challenge to clinicians serving pediatric patients and spective safety studies of pediatric pharmacotherapy.
similarly challenged the authors. Ethanol is commonly This list represents a single step in the ongoing work
used as an excipient to enhance solubility of drugs in of clinicians and researchers to continuously improve
solution and prevent microbial growth. Its use in liquid drug safety for children.
medications for children, both intravenous and oral,
has been a cause for concern for decades.63,64 In 1984, Article Information
the American Academy of Pediatrics (AAP) published Affiliations. St. Louis Children’s Hospital (CM, KPM), St. Louis,
recommendations on limits for alcohol concentrations MO; Washington University School of Medicine (CM), St.
in over-the-counter medications, and the FDA has sim- Louis, MO; Swedish Orphan Biovitrum AB (CM), Stockholm,
ilar recommendations published in the Federal Regis- Sweden; Ernest Mario School of Pharmacy, Rutgers University
ter.64,65 Despite the recommendations from the AAP (RSM), Piscataway, NJ; Saint Barnabas Medical Center (RSM),

Downloaded from https://jppt.kglmeridian.com at 2025-08-03 via free access

and FDA on limits for over-the-counter medications, Livingston, NJ; Memorial Sloan Kettering Cancer Center (JT),
New York, NY; Pediatric Mental Health Institute at Children’s
no recommendations exist for prescription products.
Hospital Colorado (DLS), Aurora, CO; University of Colorado
In a study published in 2024, seven medications used
Skaggs School of Pharmacy & Pharmaceutical Sciences
in pediatric patients were shown to have the poten- (DLS), Aurora, CO; University of Colorado School of Medicine
tial to increase blood alcohol concentrations above (DLS), Aurora, CO; Comer Children’s Hospital (SJS), Chicago,
2.5 mg/dL, which is approximately equivalent to the IL; UChicago Medicine (SJS), Chicago, IL; Children’s Health
concentration an adult would experience upon con- (KP), Dallas, TX; Phoenix Children’s Hospital (RCH); Phoe-
sumption of 10 mL of wine.19 While the clinical impli- nix, AZ; Monroe Carrell Jr. Children’s Hospital at Vanderbilt
cations of increased blood alcohol concentrations in (ALP), Nashville, TN; Southern Illinois University Edwardsville
infants and children remain theoretical, the high con- School of Pharmacy (LB), Edwardsville, IL; Cardinal Glennon
centrations found in some medications for children Children’s Hospital (LB), St. Louis, MO; University of Rhode
Island College of Pharmacy (KLM), Kingston, RI; UMass Me-
remain a concern. The current KIDs List recommen-
morial Health (KLM), Worcester, MA; Independent Consultant
dation mirrors the limits from the FDA for over-the-
(DSH), Lakeville, MN.
counter products, but more data on its risks would
help provide clarity on safe limits. Notably, no com- Correspondence. David S. Hoff, PharmD;
plete list of drugs containing benzyl alcohol, ethanol, [email protected]
propylene glycol, and other excipients exists. We con-
sidered excipients individually and included available Disclosure. The authors declare no conflicts or financial in-
information, with a specific focus on thresholds for terest in any product or service mentioned in the manuscript,
toxicity. Clinicians must remain diligent in identifying including grants, equipment, medications, employment,
the presence and concentration of these excipients in gifts, and honoraria. The authors had full access to all the
data and take responsibility for the integrity and accuracy
drugs prescribed to pediatric patients.
of the data analysis. All authors attest to meeting the four
criteria recommended by the ICMJE for authorship of this
Conclusions
manuscript.
An extensive review of primary literature and tertiary
references, followed by a robust panel discussion of Ethical Approval and Informed Consent. Given the nature
pediatric pharmacotherapy specialists, facilitated an of this study, institutional review board/ethics committee
updated list of drugs and excipients that should gen- ­approval was not required.
erally be avoided or used with caution in all or select
subgroups of pediatric patients. The first edition of Acknowledgments. The panel wishes to acknowledge the
organizational support of the Pediatric Pharmacy Associa-
the KIDs List has served as a valuable tool to improve
tion (PPA) in the creation of this manuscript. We appreciate
drug safety for children, functioning as an evidence-
Wolters-Kluwer Clinical Drug Information, Inc. for their gener-
based reference of the risks associated with relatively ous assistance with use and a query of the UpToDate Lexidrug
contraindicated drugs in the pediatric population. databases. This manuscript is endorsed by the Pediatric
The list also has served as a reference to combat Pharmacy Association (PPA) and Institute for Safe Medication
historical dogma, accurately reflecting the rationale Practices (ISMP).
and level of evidence supporting contraindications
and highlighting knowledge gaps in the published Submitted. May 15, 2025
literature. Recommendations have been revised from
the 2020 publication, based on novel research and Accepted. May 15, 2025

www.jppt.org J Pediatr Pharmacol Ther 2025 Vol. 00 No. 00 13

PPA 2025 KIDs List McPherson, C et al

Copyright. Pediatric Pharmacy Association. All rights reserved. 16. By the American Geriatrics Society Beers Criteria Up-
For permissions, email: [email protected] date Expert Panel. American Geriatrics Society 2023
updated AGS Beers Criteria(R) for potentially inappro-
Supplemental Material. DOI: 10.5863/JPPT-25-00061.S1 priate medication use in older adults. J Am Geriatr Soc.
DOI: 10.5863/JPPT-25-00061.S2 2023;71(7):2052–2081.
17. Rochon PA, Hilmer SN. The Beers Criteria then and now.
J Am Geriatr Soc. 2024;72(1):3–7.
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