Topic Resources
Drug treatment in children differs from that in adults, most obviously because pediatric drug dosing is usually based on weight or body surface area (1). Doses and dosing intervals differ because of age-related variations in drug absorption, distribution, metabolism, and elimination (see Pharmacokinetics in Children) (2). Consequently, children are not usually given adult doses. Furthermore, since dosing does not always follow a linear relationship with weight, it cannot be assumed that a child’s dose is proportional to an adult’s dose (ie, that a 7-kg child requires 1/10 the dose of a 70-kg adult).
Most drugs have not been adequately studied in children, but, legislation in the United States, the Best Pharmaceuticals for Children Act (BPCA) of 2001 and the Pediatric Research Equity Act (PREA) of 2003 (both made permanent in 2012 [3]) now provide the statutory and regulatory authority to incentivize and require therapeutic trials in children. As a result of these Acts, numerous labeling changes were made to provide dosing, pharmacokinetic, and safety information for children (4). Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that required postmarketing pediatric surveillance studies, but only 33.8% of the mandated studies were completed by December 2017, leaving significant gaps in pediatric efficacy, safety, or dosing information in drug labels (5). Efforts to improve pediatric drug labeling and utilization continue.
General references
1. Le J, Bradley JS: Optimizing antibiotic drug therapy in pediatrics: Current state and future needs. J Clin Pharmacol 58 (supplement 10):S108–S122, 2018. doi: 10.1002/jcph.1128
2. van den Anker J, Reed MD, Allegaert K, Kearns GL: Developmental changes in pharmacokinetics and pharmacodynamics. J Clin Pharmacol 58 (supplement 10):S10–S25, 2018. doi: 10.1002/jcph.1284
3. Bourgeois FT, Kesselheim AS: Promoting pediatric drug research and labeling—Outcomes of legislation. N Engl J Med 381(9):875–881, 2019. doi: 10.1056/NEJMhle1901265
4. U.S. Food and Drug Administration: Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. 2020 status report. Updated April 21, 2022. Accessed June 6, 2025.
5. Hwang TJ, Orenstein L, Kesselheim AS, Bourgeois FT: Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act. JAMA Pediatr 173(1):68–74, 2019. doi:10.1001/jamapediatrics.2018.3416
Adverse effects and toxicity
Children are generally subject to the same adverse effects as adults (see Adverse Drug Reactions), but they have an increased risk with certain drugs because of differences in pharmacokinetics or because of drug effects on growth and development. The KIDs list refers to the "Key Potentially Inappropriate Drugs" and is a resource for clinicians that includes drugs and excipients that may be inappropriate in pediatric patients due to adverse effects or toxicity (1). Some common drugs with unique or higher risk of adverse effects in children are listed in table Some Drugs Manifesting Differential Toxicity in Children.
Some Drugs Manifesting Differing Toxicity in Children
Drug | Clinical Syndrome | Mechanism | Comments |
|---|---|---|---|
Anesthetics, topical (eg, benzocaine, mixture of lidocaine and prilocaine)Anesthetics, topical (eg, benzocaine, mixture of lidocaine and prilocaine) | Cyanosis | Formation of methemoglobin (ferrous iron oxidized to ferric iron) | Incidence rare |
CeftriaxoneCeftriaxone | Bilirubin displaced from albumin | Caution in neonates | |
Codeine*Codeine* | Respiratory depression Death | Ultrarapid metabolization of codeine to morphine | Genetic variant, avoid use without pharmacogenomic testing Deaths have occurred after surgery and in a breastfed infant whose mother took codeine |
Diphenoxylate | Respiratory depression Death | CNS depression (in immature CNS) | Overdose syndrome, usually in children < 6 years |
Fluoroquinolones | Cartilage toxicity, joint pain | Unknown | Suspected based on animal studies, but adverse effects in humans not well documented; short-term use or use when there is no alternative may be safe |
Lindane (topical)Lindane (topical) | Seizures CNS toxicity | Probably enhanced absorption in children | Should not be used in children < 50 kg (alternative should be used) |
PropofolPropofol | Propofol-related infusion syndrome† | Unknown, possibly related to mitochondrial dysfunction | Higher risk in children than adults, especially with extended duration of use and high doses |
Selective serotonin reuptake inhibitors | Suicidal ideation | Unknown | Increased incidence of suicidal ideation in children and adolescents |
Sulfonamides (eg, sulfamethoxazole) | Kernicterus | Bilirubin displaced from albumin | Should not be given in neonates and infants < 2 months |
TetracyclineTetracycline | Discoloration and pitting of tooth enamel | Chelation with calcium in growing teeth | Not given to children < 8 years |
* See also the American Academy of Pediatrics' clinical report about codeine metabolism in children. | |||
† Propofol-related infusion syndrome is a rare, potentially fatal complication of prolonged (> 48 hours), high-dose propofol infusions that cause severe metabolic acidosis, hyperkalemia, and cardiac failure.-related infusion syndrome is a rare, potentially fatal complication of prolonged (> 48 hours), high-dose propofol infusions that cause severe metabolic acidosis, hyperkalemia, and cardiac failure. | |||
CNS = central nervous system. | |||
Younger children are at especially high risk of accidental poisoning if they discover and take their caregivers’ vitamins or medications, even vitamins and medications that have been thrown away. When discarding a medication, consumers may seek disposal instructions on the package insert or review information from the FDA (2). Options include taking the medication to a local drug collection program (possibly at a pharmacy or local law enforcement site) or when such take-back options are not available, mixing the drug with an undesirable material (eg, cat litter, coffee grounds), placing it in a sealable, watertight container or bag, and then disposing of it in the trash.
Infants may also be at risk of toxicity from medications used by adults. Toxicity in infants may occur either prenatally when they are exposed via placental transfer or postnatally when exposed through breast milk (numerous agents—see Medications and Breastfeeding and table Some Medications Contraindicated for Breastfeeding Mothers). Because there are limited data regarding the potential for drug exposure during pregnancy and lactation, the 21st Century Cures Act established a task force to identify gaps in knowledge and research on safe and effective therapies for pregnant women and lactating patients (3).
Other types of inadvertent exposure include skin contact with caregivers who have recently applied certain topical drugs (eg, scopolamine for motion sickness, malathion for lice, diphenhydramine for poison ivy).Other types of inadvertent exposure include skin contact with caregivers who have recently applied certain topical drugs (eg, scopolamine for motion sickness, malathion for lice, diphenhydramine for poison ivy).
Adverse effects, including death, have occurred in children receiving over-the-counter cough and cold preparations containing some combination of an antihistamine, sympathomimetic decongestant, and the antitussive dextromethorphan (Adverse effects, including death, have occurred in children receiving over-the-counter cough and cold preparations containing some combination of an antihistamine, sympathomimetic decongestant, and the antitussive dextromethorphan (4). The FDA does not recommend over-the-counter cough and cold preparations in children < 2 years old (5). Manufacturers voluntarily extended labeling to advise against use in children < 4 years, this more restrictive recommendation aligns with the recommendation from the American Academy of Pediatrics.
Adverse effects and toxicity references
1. Meyers RS, Thackray J, Matson KL, et al: Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther 25(3):175–191, 2020. doi:10.5863/1551-6776-25.3.175
2. U.S. Food and Drug Administration: Where and How to Dispose of Unsued Medicines. April 16, 2025. Accessed June 6, 2025.
3. U.S. Food and Drug Administration: 21st Century Cures Act. January 31, 2020. Accessed June 6, 2025.
4. Halmo LS, Wang GS, Reynolds KM, et al: Pediatric fatalities associated with over-the-counter cough and cold medications. Pediatrics 148(5):e2020049536, 2021. doi: 10.1542/peds.2020-049536
5. Yin HS, Neuspiel DR, Paul IM, et al: Preventing Home Medication Administration Errors. Pediatrics 148(6):e2021054666, 2021. doi:10.1542/peds.2021-054666
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.
U.S. Food and Drug Administration (FDA): Best Pharmaceuticals for Children Act and Pediatric Research Equity Act status report (2020)
FDA: The Task Force on Research Specific to Pregnant Women and Lactating Women: Report to Secretary, Health and Human Services, Congress. September 2018. Accessed June 4, 2025.
American Academy of Pediatrics: Codeine: Time to Say “No”
Drugs Mentioned In This Article
