Essential drugs for infants and children: North American perspective.

“Essential Drugs for Children” implies that some drugs are not essential, which of course, is true. It also implies that essential drugs can and should be differentiated from “nonessential” drugs and targeted as a priority for development for pediatric use. With ;80% of the marketed prescription drugs in the United States not approved by the US Food and Drug Administration (FDA) for use by children, the goal of obtaining approval and labeling for all drugs currently not labeled for use by children is overwhelming. Therefore, drugs currently available must be prioritized for pediatric development so that available resources can be focused on those agents most important for pediatric use. This is a daunting task. How is an essential drug defined? What are the criteria for selecting essential drugs? Is it the volume of use? Is it the number of children impacted by the drug? Is it the indication(s) for use? Is it the severity of the condition for which the drug is indicated? Is it a drug used to treat a life-threatening condition? For the child with bacterial meningitis, the appropriate antibiotic clearly is essential. For the child with HIV infection or cancer, drugs that will impede progression of the disease, prolong life, and mitigate suffering are essential. A drug used to treat a rare genetic disorder is essential for the child affected by that disorder, although it may have minimal impact on the health of the general population of children. In contrast, an effective vaccine will have profound direct benefit for the entire population. A drug used to treat symptomatically the selflimiting pruritus associated with varicella or insect bites may be widely prescribed, although it is used to treat a relatively trivial condition. Each of some 30 odd subspecialties, if queried, undoubtedly would have its list of essential drugs. Advocates of treatments for rare diseases view certain drugs as essential, although they may be used in relatively few children and may not ensure long-term survival in all cases. How does one factor in these various considerations when developing criteria for prioritizing drugs for pediatric development? Determining how essential drugs are to be defined is a complex issue. At the same time, developing a definition and process for agreeing on the most important drugs for children is imperative when attempting to prioritize the plethora of drugs used by children but for which pediatric labeling and/or dosage formulations do not exist. This certainly is not a new or novel issue. Indeed, several abortive attempts have been made during the past 20 years to identify drugs most important to children. In 1979, under a contract with the FDA, the American Academy of Pediatric (AAP)’s Committee on Drugs compiled a list of several hundred drugs in 33 therapeutic categories that were judged to be useful for pediatric patients but not labeled for pediatric age groups. This report was filed with the FDA in June 1979. No attempt was made to prioritize among the hundreds of drugs. No official action on the part of the FDA was ever taken. The AAP Committee on Drugs, under contract with the FDA, compiled a second list of 103 drugs in 1984 that represented drugs used commonly in infants by parenteral routes but were not labeled for infants. This list included dexamethasone, diazepam, digoxin, dopamine, erythromycin, furosemide, gentamicin, indomethacin, morphine, naloxone, pancuronium, penicillin, phenobarbital, theophylline, vancomycin, and vitamins B12, E, K plus many more. Again, no attempt was made to prioritize within this list. In response to the 1984 list, the FDA requested a list of the 10 most important parenterally administered drugs for neonates. This top 10 list was prepared and filed with the FDA in January 1985. Selection was based on two levels of criteria. Criteria for level I selection of drugs were 1) the drug was currently used in therapy of neonates; 2) it was anticipated that use would continue and therapeutic value was documented; 3) existing published data were available regarding dosage recommendations, therapeutic indications, and toxicity; and 4) current labeling for neonatal use did not exist. If these four conditions were met, level II priority assignment was based on 1) frequency of use; 2) low therapeutic index; and 3) significant or serious toxicities reported with drug. Drugs included on this list were phenobarbital, dopamine, dobutamine, theophylline, nitroprusside, calcium, pancuronium, ampicillin, caffeine, and indomethacin. This lead to modest progress; pediatric information subsequently was added to 5 From the Departments of Pediatrics and Pharmacology, Children’s Mercy Hospital, University of Missouri–Kansas City, Kansas City, Missouri. This paper was presented at the International Symposium The Therapeutic Orphan—30 Years Later; May 2, 1997; Washington, DC. Received for publication Mar 30, 1999; accepted Mar 31, 1999. Address correspondence to Ralph E. Kauffman, MD, Director, Office of Medical Research, Children’s Mercy Hospital, Division of Medical Research, 2401 Gillham Rd, Kansas City, MO 64108. PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Academy of Pediatrics.