Drug treatment in children differs from that in adults, most obviously because pediatric drug dosing is usually based on weight or surface area (1). Doses (and dosing intervals) differ because of age-related variations in drug absorption, distribution, metabolism, and elimination (see Pharmacokinetics in Children). Thus, children are not given adult doses. Furthermore, 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 federal legislation (the Best Pharmaceuticals for Children Act of 2001 and the Pediatric Research Equity Act of 2003, both made permanent in 2012—2; see also the U.S. Food and Drug Administration [FDA] 2016 status report) now provides the statutory and regulatory authority to incentivize and require therapeutic trials in children. As a result of this legislation, numerous labeling changes were made to provide dosing, pharmacokinetic, and safety information for children.
General references
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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
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2. Connor EM, Smoyer WE, Davis JM, et al: Meeting the demand for pediatric clinical trials. Sci Transl Med 6(227):227fs11, 2014. doi: 10.1126/scitranslmed.3008043
Adverse effects and toxicity
Children are generally subject to the same adverse effects as adults (see Adverse Drug Reactions), but they have increased risk with certain drugs because of differences in pharmacokinetics or because of drug effects on growth and development. Some common drugs with unique or higher risk of adverse effects in children are listed in table Drugs Manifesting Differential Toxicity in Children.
Drugs Manifesting Differing Toxicity in Children
Drug |
Clinical Syndrome |
Mechanism |
Comments |
|
Anesthetics, topical (eg, benzocaine, mixture of lidocaine and prilocaine) |
Cyanosis |
Formation of methemoglobin (ferrous iron oxidized to ferric iron) |
Incidence rare |
|
Ceftriaxone |
Bilirubin displaced from albumin |
Affects only neonates |
|
|
Codeine* |
Respiratory depression Death |
Ultrarapid metabolization of codeine to morphine |
Genetic variant 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 < 2 years |
|
Fluoroquinolones |
Cartilage toxicity |
Unknown |
Suspected based on animal studies, but adverse effects in humans unproved—short-term use may be safe |
|
Lindane (topical) |
Seizures CNS toxicity |
Probably enhanced absorption in children |
Should not be used in children < 50 kg (alternative should be used) |
|
Prochlorperazine |
Altered CNS function Extrapyramidal effects Opisthotonus Bulging fontanelles |
Actions via multiple CNS receptors |
Febrile and dehydrated infants especially at risk |
|
Selective serotonin reuptake inhibitors |
Suicidal ideation |
Unknown |
Increased incidence of suicidal ideation in children and adolescents |
|
Tetracycline |
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. |
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CNS = central nervous system. |
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Younger children are at especially high risk of accidental poisoning when they discover and take caregivers’ vitamins or drugs, even vitamins and drugs that have been thrown away. When discarding a drug, consumers may seek disposal instructions on the package insert or review information at the Food and Drug Administration's web site). Options include taking the drug to a local drug collection program (possibly at a pharmacy or local law enforcement site) or mixing the drug with an undesirable material (eg, cat litter, coffee grounds), tightly wrapping it in plastic, placing it in a watertight container or bag, and disposing it in the trash.
Infants may be at risk of toxicity from drugs used by adults; toxicity may occur prenatally when they are exposed via placental transfer or postnatally when exposed through breast milk (numerous agents—see Breastfeeding : Drugs and Breastfeeding and see Table: Some Drugs 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 women (1).
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. Current recommendations are that such products should not be given to children < 4 years.
Adverse effects and toxicity reference
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1. The Task Force on Research Specific to Pregnant Women and Lactating Women: Report to Secretary, Health and Human Services, Congress. September 2018.
More Information
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
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U.S. Food and Drug Administration (FDA): Best Pharmaceuticals for Children Act and Pediatric Research Equity Act
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FDA: FDA Reauthorization Act of 2017 (FDARA)
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American Academy of Pediatrics: Codeine: Time to Say “No”
