CHAPTER 13

Principles of Pediatric Therapeutics

Bonnie R. Rachman, MD

A drug or therapeutic can be defined as any substance that is ingested, absorbed, or injected that alters the body’s function. Examples include prescription medications, over-the-counter (OTC) medications, homeopathic preparations, herbal remedies and teas, vitamin supplements, and illicit substances. Different drug categories have differing safety profiles and regulation levels. Prescription drugs are the most regulated. Homeopathic preparations, some vitamin formulations, and most herbal remedies may have little, if any, standardization, safety testing, or regulation. Illicit drugs have no quality testing.

The use of prescription and OTC medications is very common in pediatrics. The Slone Survey, a random digit-dial survey of medication use, found that families with children reported that more than 55% of children younger than 12 years had taken some medication preparation within the last 7 days. Of those taking a medication, 22% were taking at least 1 prescription medication. In a given month, more than 50% of preschool-age children had received some OTC medication. In 2011 to 2012, 7.5% of US children and teenagers aged 6 to 17 years took medication for emotional or behavioral difficulties. The number of children aged 12 years and younger being administered an OTC medication in a given period is more than twice that of a prescription medication. The most commonly used OTC medications are acetaminophen and ibuprofen. In the adolescent age group, aged 12 to 17 years, more OTC products are used for acne and less for allergies or pain relief. Given that the use of OTC medications is so prevalent and that many OTC medications contain multiple active ingredients, concerns about their safety profile for children is an issue that needs to be addressed by pediatricians with families at routinely scheduled office visits as well as by regulatory agencies.

Another concern is the use of prescription or OTC medications as drugs of abuse. Of particular concerns are adolescents who use alcohol, illicit drugs, and medications, including OTC cough medications containing dextromethorphan. In the 2017 Monitoring the Future survey of 8th, 10th, and 12th graders nationwide, approximately 3% of the survey participants reported using OTC cough medicine to “get high” in the past year. Also, in the past year, 49% reported use of alcohol, 28% reported use of marijuana, 61.3% reported use of Vicodin, and 1.9% reported use of oxycodone.

Furthermore, according to the Centers for Disease Control and Prevention, each year more than 60,000 children are brought to the emergency department (ED) for medication overdoses; OTC medications were implicated in more than 26,000 visits. Ninety percent of ED visits for medication overdoses resulted from unsupervised ingestions of prescription and OTC drugs, with peak incidence in the younger-than-5-year age group.

Most drugs prescribed for children have not been tested in children. Before the US Food and Drug Administration (FDA) initiated a pediatric program (Best Pharmaceuticals for Children Act of 2002 [amended in 2007]), only about 20% of drugs approved by the FDA were labeled for pediatric use. Currently, about one-third of drugs prescribed to children have been studied for safety and efficacy in pediatric populations. The practice of prescribing drugs for off-label conditions is found in approximately 50% of all physician prescriptions. By necessity, doctors have routinely given drugs to children off-label, which means the drug has not been approved for use in children based on the demonstration of safety and efficacy in adequate, well-controlled clinical trials. It does not imply that the drugs are unsafe, improper, or illegal. The Pediatric Research Equity Act of 2003 (amended in 2007) requires pediatric studies and covers drugs and biologics. Under the Pediatric Research Equity Act, the FDA can require pediatric studies of a drug submitted in a new drug application if it determines the product is likely to be used in a substantial number of pediatric patients or if the product would provide a meaningful benefit in the pediatric population over existing treatments. In a systematic review of the frequency of off-label use of antibiotics in clinical pediatric practice, the percentage of off-label antibiotic prescriptions varied from 1% to 94%. Some of the wide variation observed in pediatric patients might be attributed to the heterogeneity among the study populations’ ages of children.

Off-label use creates a liability for the physician. The burden of an adverse outcome is on the manufacturer or license holder when there is an on-label use of a medication and an iatrogenic injury is sustained. When the medication is prescribed off-label, legal liability is on the prescriber unless parents and/or guardians are appropriately informed and give their consent.

Differences in pharmacokinetics among infants, children, and adolescents can result in differences in drug efficacy and toxicity. To choose the most important therapeutic, health care professionals must consider a number of factors, including patient characteristics, disease epidemiology, safety profile, patient compliance, and cost-effectiveness (Box 13.1).

Patient Characteristics

Infants and children have different physiological characteristics than adults, including immaturity of metabolic and organ function. Body weight and surface area are considerations in drug dosing for pediatrics. In addition, the therapeutic window for many drugs is smaller for children than adults. Pharmacological factors, including age-based variability in absorption, metabolism, and excretion of drugs in children compared with adults, as well as age-specific contraindications of certain medications, pose special vulnerabilities for children to the adverse effects of overdosing. Conversions of doses from ingredient amounts to volumes for liquids labeled for home use are also problematic.

The patient’s medical history plays an important part in the choice of an appropriate therapeutic. Depending on the patient’s condition and medical and surgical history, the absorption, metabolism, or usual effectiveness of a therapeutic may be altered. Children with short bowel syndrome can potentially have difficulty absorbing oral medications depending on which portion of the bowel was removed. Children with intellectual disability who are given central nervous system–altering medications can be difficult to monitor for changes in mental status seen with systemic infection. In addition, children with glucose-6-phosphate dehydrogenase deficiency can suffer from drug-induced hemolytic anemia when given certain drugs, such as sulfonamides. Children who are malnourished are at greater risk for drug toxicity because low serum albumin levels decrease the amount of bound drug and result in increased levels of unbound drug in circulation.

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