Prescribing Medications in Pediatrics: Concerns Regarding FDA Approval and Pharmacokinetics

By Novak, Emily; Allen, Patricia Jackson

Prescribing medications “off-label” is a common practice in pediatric health care since many medications lack U.S. Food and Drug Administration (FDA) approval for pediatric drug labeling due to insufficient drug testing in children. This clinical paper reviews the FDA laws regarding approval of medications in children and the pharmacokinetic differences in absorption, distribution, metabolism and excretion between children and adults. Two commonly used pharmacology resources were reviewed to determine their identification of FDA approved indications in children and dosing recommendations by age or weight in children. Adhering to the “community’s standard of care” is a common guideline for prescribing “off-label” in pediatrics, but must be used in combination with multiple respected pediatric resources and with full knowledge of pharmacokinetics in children, particularly in young children.

Prescribing medications to the pediatric population can be a worrisome task when the weight of the prescribing climate is fully acknowledged. There still exists a knowledge deficit about drug disposition in children despite the many advances made by the pharmaceutical industry and recent changes in legislation that attempt to improve drug labeling for children. Many drugs have not been adequately tested in children and implementing universal, scientifically rigorous drug testing in children is certainly not without its own set of risks. Children are physiologically different from adults; therefore, drug studies conducted in adult populations cannot be simply extrapolated to pediatric populations. Understanding the age-associated physiological differences in children is a guiding prescribing principle for pediatric providers. The purpose of this paper is to assist pediatric primary care providers to safely prescribe pharmacotherapy while understanding the limitations of U.S. Food and Drug Administration (FDA) approval and “offlabel” use in infants, children and adolescents and the accuracy of commonly used pharmacology resources in identifying FDA approval for uses in pediatric patients.

Method

Literature and data reviewed in this paper were retrieved from Medline and CINAHL electronic databases using the following keywords: Off-label, unapproved use, unlicensed used, therapeutic orphan, pediatric drug labeling, package inserts, drug labels, pediatric drug research, pediatric drug testing, FDA drug regulation, pediatric drug regulation, and pediatric therapeutics. An ancestry search was also conducted using relevant articles as a basis. Information and data were retrieved from electronic U.S. government databases and Google Scholar databases. Primary source text book chapters were reviewed, as well as current peerreviewed professional journals.

Drug Labeling and “Off-Label” Use

New drugs are continually being developed by the pharmaceutical industry and are often FDA approved for adult use with inadequate drug labeling of the indications for use in children. This results in either no dosing information for pediatric patients or explicit disclaimers stating that safety and efficacy have not been established in children or only in certain age groups (Blumer, 1999; Steinbrook, 2002). Medications for infants and young children are most likely to have inadequate drug labeling (Roberts, Rodriguez, Murphy, & Crescenzi, 2003). This is of concern for pediatric providers because any drug that is not specifically labeled for use in children, but is prescribed to children, or used in any other manner outside of the product’s approved labeling, is considered to be prescribed “off-label” (Roberts et al., 2003; ‘t Jong et al., 2000). The percentage of medications that do not have adequate pediatric “drug labeling” and are therefore prescribed “off-label” is still debated and changes continuously as new medications, or new uses of old medications, are developed. Prescribing “off-label” is routine in pediatric practice, particularly in hospital and specialty settings, and often involves educated guesswork about dosing, safety and efficacy (Steinbrook, 2002). However, “off- label” prescribing decisions must still rely on rational scientific theory, sound medical judgment, or data from controlled clinical trials (Blumer, 1999). Also, it is the responsibility of the prescriber to be familiar with the medication’s potential contraindications, precautions, and warnings as listed on the FDA- approved product insert (Blumer, 1999).

Medications must be extensively studied for their safety and efficacy before they can receive FDA approval (Adcock, 2006; Steinbrook, 2002). However, the majority of studies are conducted in adult populations and the findings cannot be simply adjusted by weight for use in children due to physiologic differences between adults and children (Adcock, 2006; McKinney, 2003). Clinicians could prescribe with more confidence if there were drug testing in pediatric populations, but there are barriers to conducting drug research in children. Some of the ethical dilemmas that arise with such research include the potential health risks to children participating in research, potential exploitation of children by the drug researchers, and the need to obtain parental consent and child assent to participate in the study. Ultimately, the goals of conducting pediatric pharmacotherapy studies are to protect children from potentially harmful medications and to provide clear safety and efficacy profiles of the medications in children (Steinbrook, 2002). However, the potential risk for the individual participants may be significant and can outweigh any long-term benefits for the individual and the greater pediatric population.

In order for a medication to be sold and prescribed, there is a legal requirement that the medication have an appropriate “drug label” that contains indication for adult use, but pediatric labeling is not required for marketing or use (Wilson, 1999). These drug labels produced by the drug manufacturers, as well as package inserts, are FDA regulated to ensure that they are congruent with the specific FDA approved indications (American Academy of Pediatrics [AAP], Committee on Drugs, 1996; Blumer, 1999). Drug labels including package inserts are intended to include all pertinent information regarding the drug’s safety and efficacy, including the indications for use (AAP, Committee on Drugs (1996). However, there is still not an FDA requirement for pediatric drug labeling even though drug labeling for children would be beneficial for health care providers and would increase the safety and efficacy of drug use in children.

FDA-approved pediatric drug labeling would provide information in a useable format that demonstrates substantial evidence of the efficacy, safety and age-dependent dosing indications in infants, children, and adolescents (Wilson, 1999). The FDA cannot regulate how a drug is ultimately prescribed once it has FDA approval for a specific use because it is forbidden to interfere with how medicine is practiced. Thus, any licensed prescriber can prescribe an FDAapproved medication for any use, although this could be grounds for malpractice if the drug use does not adhere to the “community’s standard of care” (Blumer, 1999). Comprehensive FDA-approved pediatric drug labeling would help protect pediatric providers from malpractice suits since “off-label” use of medications is often a component of legal proceedings (Wilson, 1999). For parents, the presence of FDA-approved pediatric drug labeling may help to ensure insurance coverage for necessary medications.

There are few incentives for pharmaceutical companies to conduct pediatric drug testing. This is largely attributed to the small market share that exists for drugs with pediatric indications. Without anticipated profits motivating new drug research, pharmaceutical companies lack the drive to conduct studies for a small population and profit margin (McKinney, 2003). Also, the complexity of the studies that would be required due to physiological differences between adults and children, and among varying age groups of children, discourages pharmaceutical companies from conducting pediatric drug studies. The FDA, the pharmaceutical industry, Congress, and the AAP have attempted to rectify the situation over the years, but still only one-third of the drugs used to treat children have been adequately studied in a pediatric population and have the appropriate use on the product label (Roberts et al., 2003).

History of Pediatric Drug Regulation by the FDA

In the United States, drug regulation first began in 1906 with the advent of the Federal Food and Drugs Act. This Act was likely the result of the large number of soldiers killed from adulterated quinine as well as in response to a significant number of children who were exposed to tainted food products. From this point forward the driving force behind changes in drug regulations was largely due to adverse outcomes of pharmacotherapy in children. In 1938, in response to the death of nearly 100 children, from sulfanilamide elixir, an amendment to the Federal Food and Drugs Act was enacted requiring truthfulness in labeling and documentation \of safety of drugs. Diethylene glycol was in the elixir and was later found to be the offending chemical. The 1938 Food and Drugs Act initiated the new drug application (NDA) process that requires toxicity studies be conducted before a drug can be marketed or distributed (Blumer, 1999; Woo, 2004).

It was not until the infamous thalidomide mishap of the 1960s that stricter regulations about drug testing came into effect. Previously, there had been no requirements for drug testing in humans. Thalidomide was prescribed to combat morning sickness in pregnancy, but was later found to have teratogenic effects in humans resulting in a large number of children born with physical deformities. The Harris-Kefauver Amendment was written in 1962, requiring preclinical trials before drug testing in humans. This Amendment established the current three-phase investigational new drug (IND) process. In Phase I, drugs are tested to establish their safety and pharmacokinetics; in Phase II, drugs are tested for therapeutic efficacy and dose range; in Phase III, comparative clinical trials take place to ensure further drug safety and efficacy (Blumer, 1999; Woo, 2004). It is typically not until Phase III that the FDA requests that pediatric studies be performed (Cote, Kauffman, Troendle, & Lambert, 1996). After preclinical testing, which includes in-vitro and animal testing, an application is submitted for FDA review, and if approved, the three phases of human clinical testing take place. The result of this process is an increase in costs to the drug manufacture and time it takes a drug to get to market. It typically takes 8 to 9 years for a drug to pass from the IND through the NDA process. The delay in market availability often results in criticism of the FDA from individuals with life-threatening diseases and the practitioners who treat them. Hence, the FDA developed a solution called the “Treatment IND” that enables patients with life-threatening illness to receive drugs prior to general marketing if there are insufficient alternatives (Blumer, 1999; Woo, 2004).

It was believed that the 1962 drug amendments would increase pediatric drug labeling; however, instead the wide use of the pediatric disclaimer was adopted (Wilson, 1999). In 1979 the FDA first issued regulations requiring that pediatric information be placed on drug labels and package inserts, but still few pediatric studies were conducted. In 1994, in an attempt to increase pediatric drug labeling, the FDA allowed companies to obtain pediatric labeling if they established a dosing regimen in children where the course of the disease process was similar to adults, e.g. asthma, pneumonia (Gorman, 2003; McKinney, 2003). Despite the potential for a company to expand its market, few companies chose to pursue pediatric trials (McKinney, 2003).

In 1997 the Food and Drug Administration Modernization Act (FDAMA) was passed in attempt to create incentives for new drug testing in pediatrics. The FDAMA offered a sixmonth extension to a company’s exclusive ability to market a drug if, through the conduction of pediatric studies, it was found appropriate to alter the drug’s labeling for indications and dosing in children (McKinney, 2003). This exclusivity incentive did not apply to old antibiotics or other drugs that lacked marketing exclusivity or patent protection. This is often termed “the carrot” because it was an attempt to draw pharmaceutical companies toward a socially desirable goal.

In 1998, the Pediatric Final Rule was developed, also referred to as “the stick,” that allowed the FDA to require pharmaceutical companies to conduct pediatric studies as part of new drug development if the drug had potential for use in the pediatric population (McKinney, 2003). The Pediatric Final Rule allowed the FDA to push for pediatric studies, where previously, the pharmaceutical companies could stall the conduction of studies and ultimately choose to abstain if, toward the end of their patent, a pediatric study did not seem monetarily justifiable. Unfortunately, in 2002, the Federal District Court of the District of Columbia ruled that the FDA had overstepped its authority in the Pediatric Final Rule and overturned its ruling stating the Pediatric Final Rule made medications more expensive and would delay the release of new medications. In the same year, Congress did enact the “Best Pharmaceuticals for Children Act.” This Act extends the 6-month exclusivity extension provision to 2007 and authorized the National Institutes of Health (NIH) to work with the FDA to fund pediatric studies of drugs that no longer have exclusivity or patent protection. Then in 2003, Congress passed the Pediatric Research Equity Act that reinstated the Pediatric Final Rule (see Table 1 for a summarization of the history of pediatric drug regulation).

As of April 30, 2006 the FDA had received 467 proposed pediatric study requests and had granted 6-month exclusivity extensions to 118 drugs (FDA, 2006).

Incidence of “Off-Label” Use of Common Medications in Pediatrics

It has been estimated that approximately 75% of prescription medications in the Physician’s Desk Reference (PDR, 2006) lack appropriate pediatric labeling (AAP, Committee on Drugs, 1995, 1996; Blumer, 1999; Steinbrook, 2002; Wilson, 1999). The PDR may not be the most accurate source for identification of FDA-approved indications for pediatric use. Thomson Publisher indicated that the PDR focuses on newly available drugs and does not list older medications (Thomson Healthcare Customer Service, personal communication, April 19, 2006). Yoon, Davis, El-Essawi, and Cabana (2006), recognizing the lack of pediatric information in the PDR, reviewed all of the medications listed in the formulary of the Harriet Lane Handbook (Gunn & Nechyba, 2002), a commonly used medication reference tool in pediatric practice. They confirmed whether or not there was FDA-approved pediatric drug labeling status of each medication using the online Thompson Micromedex Healthcare Series (2006). When a medication had at least one FDA-approved indication for any therapeutic use in children (<18 years old), it was considered to be used "on-label" (Yoon et al., 2006). The "on- label" status in their study does not reflect current prescriber data on medication use in practice. This review only determined whether or not the Harriet Lane Handbook (2002) provided accurate information regarding FDA-approved pediatric use for the listed medications. Yoon et al. (2006) found only 27% of medications listed in the Harriet Lane Handbook (2002) had no FDA approval for pediatric use as compared to an estimated 75% in the PDR. When the medications in the Harriet Lane Handbook (2002) formulary were divided into 19 drug classes, e.g. antibiotics, steroids, antifungals, lack of FDA approval for pediatric use ranged from a low of 3% of the allergy/asthma class to a high of 57% of the cardiac class. This study indicated that the number of medications commonly used in pediatrics that did not have FDA approval, although still significant, was not as dramatic as previously indicated in the literature and varied appreciably by drug class.

Yoon et al. (2006) did not compare listing of drugs from the Harriet Lane Handbook (2002) to listings in the PDR for indication of FDA approval for pediatric use. Nor did their study compare these two commonly used resources for information regarding age-specific recommendations for dosing of medications in children. In fact, some medications can have FDA approval but for only older children and adolescents. For example, the PDR indicates that for some brands of inhaled albuterol the safety and efficacy of the medications has not been established in children below the age of 4 years, while other brands of inhaled albuterol in the PDR state that safety and efficacy has not been established in children below the age of 12 years. But, the Harriet Lane Handbook (Robertson & Shilkofski, 2005) indicates dosing instructions for albuterol for children less than 1 year of age and older. As pediatric primary care providers it is important to know which pharmacological resources offer the most information regarding FDA approval and age-specific dosing recommendations.

Comparison Review of Drug Information Resources

The current edition of the PDR (2006) and the Harriet Lane Handbook (Robertson & Shilkofski, 2005) were reviewed for indication of FDA-approval for pediatric use and age-specific recommended dosing for three classes of medications (antibiotics, asthma/ allergy, and topicals – ear, eye and skin). The medications were divided into classes based on their class description within the Harriet Lane Handbook (2005) formulary. The online tool Thompson Micromedex Healthcare Series (2006) was used to confirm the FDA approval for any pediatric use in children 0-18 years old. Each medication in the three classes was evaluated for the number of age- specific designations for use and dosing information. The Harriet Lane Handbook (2005) varied in how it indicates dosing recommendations; by age, including specific for neonates of varying age and gestation, by weight in kilograms, and by indications for use. When the dosing information was based on weight (kg) and not based on age, this was interpreted to mean the medication was appropriate for all age classifications. If the dosing information required a minimum weight requirement, e.g. 15 kg, this was interpreted to connote children and adolescents, but not infants and newborns. In instances where a medication was not found in the PDR of prescription medications, it was crossreferenced with the PDR for nonprescription medications and dietary supplements before it was deemed to be excluded from the PDR.

There were 78 medications in the antibiotic class, 42 medications in the asthma/allergy class, and 38 medications in the topical class. There were 8 medications listed in the Harriet Lane Handbook (20\05) that did not have FDA approval for pediatric use, 4 (5%) of the antibiotic class and 4 (11%) of the topical class. All asthma/ allergy medications were confirmed to have FDA approval for use in pediatrics. Thirty-nine antibiotics (50%), 8 (21%) of topicals, and 11 (26%) of asthma/allergy medications listed in the Harriet Lane Handbook (2005) did not have drug insert information in the PDR (2006).

Of the medications with FDA approval found in both Harriet Lane Handbook (2005) and PDR (2006), 8 (24%) of the antibiotics, 5 (20%) of the topicals, and 2 (6%) of the asthma/allergy medications had greater age-specific dosing recommendations in the Harriet Lane Handbook (2005). A few medications, 2 (6%) of the antibiotics, 1 (4%) of the topicals, and 1 (3%) of the asthma/allergy medications had more age-specific dosing recommendations in the PDR (2006).

This comparative study illustrates the importance of using multiple sources in the pediatric primary care setting to be fully informed about the medications being prescribed. The dosing recommendations in any pediatric drug resource reflect the “community standard of care” but it is still important to understand there are limitations from each resource. The Harriet Lane Handbook proves to be an excellent resource for dosing information but does not list FDA approval for medications (see Table 2). The online resource, Thompson Micromedex, a frequently updated Integrated Index System, was found most useful for determining FDA approval for pediatric use and also linked to multiple pharmacology resources and, therefore, can be used as a search engine for those providers who have internet access on site. Use of the PDR is limited to newer medications and therefore, is less helpful to the pediatric provider.

Pharmacokinetics of Medications in Children

There is no exact science to determine the appropriate medication or dosage for all children with all conditions. Pediatric providers must use multiple resources in guiding their pharmacotherapy. In addition, pediatric clinicians must understand how physiological development affects absorption, distribution, metabolism and excretion in children. (Adcock, 2006). Age is one of the most important variables to influence how drugs are processed and their subsequent effect on the body (Behrman, Kleigman, & Jensen, 2004). Childhood is an unstable and dynamic period due to the ongoing processes of growth and development. These ongoing changes in body and organ functions influence both drug effects and disposition (Ebert, 2003). This is particularly true for the neonatal and infancy periods when the most rapid and significant physiologic changes are occurring (see Table 3 for summary of physiological differences between children and adults and drug absorption, distribution, metabolism and excretion).

Absorption. Drug absorption in infants and children are affected by three factors that are distinct from adults – gastrointestinal (GI) function, blood flow at the site of administration and skin permeability. Infants have proportionately larger small intestine surface areas than adults which can lead to unpredictable absorption patterns in comparison to adults (Woo, 2004). Neonates have prolonged emptying time and irregular peristalsis that can lead to erratic absorption rates and altered serum peak concentrations leading to inadequate dosing (Sagraves, 1995; Suggs, 2000). The GI emptying time will not reach adult levels until 6-8 months (Suggs, 2000; Zenk, 1994). Additionally, neonates have a decreased gastric pH, which affects the absorption of medications. Gastric pH reaches adult levels by 1 to 3 years of age. Overall, by the age of 10-12 years the GI tract is equivalent to that of an adult. However, puberty is a developmental stage with the potential for unpredictable and poor eating habits, thereby affecting absorption (Suggs, 2000).

The second factor that affects drug absorption is regional blood flow at the site of administration, particularly for intramuscular (IM) medications. Infants and children have erratic blood flow to tissue that can cause decreased absorption rates (Suggs, 2000).

The third factor is the greater permeability of the skin of newborns and infants. The skin has a greater ability to absorb some chemicals because of increased hydration and increased permeability due to a thinner, more permeable, skin stratum (Edmunds & Mayhew, 2004). The surface area percentage of children is three times that of an adult, therefore, topically administered medications have greater potential for absorption into the systemic circulation (Suggs, 2000).

Distribution. There are three main factors that can affect drug distribution in infants and children – differences in body composition, low blood plasma protein concentrations and immaturity of physiological barriers. Neonates and infants have a higher percentage of total body water than adults (70%-80% vs. 60% in an adult) and a lower body fat composition (Woo, 2004). This affects some drug dosing and therefore hydrophilic drugs may be dosed at higher levels to achieve the necessary serum concentrations, while lipid soluble drugs may have a decreased dose (Suggs, 2000; Woo, 2004). Puberty changes body composition leading to difficulty in dosing, particularly in adolescent boys as lean body mass increases and fat decreases (Woo, 2004).

Decreased plasma proteins in infants less than 6 months of age greatly reduce the ability for drug binding. This results in higher levels of unbound medication and thus drug toxicity even in the presence of normal or low plasma concentration of the total drug (Woo, 2004). Therefore, dosing must again be modified. Adult plasma protein levels are reached by the age of 12 months (Suggs, 2000).

The immaturity of the blood-brain barrier must also be taken into account in neonates. The blood-brain barrier is not complete at birth, thereby increasing the permeability to medications resulting in amplified central nervous system drug effects (Suggs, 2000). Again, drug dosing must be altered to take this difference into account.

Metabolism. Metabolism of drugs occurs through either metabolic or enzymatic reactions. The liver is the primary organ for drug metabolism, although the lungs, kidneys, blood, gastrointestinal tract, and skin are also important sites of metabolism (Blaho, Winbery, & Merigian, 1996; Suggs, 2000; Zenk, 1994). During the first year of life there is a delay in the maturation of drug- metabolizing enzymes that likely accounts for drug toxicity in the very young infant (Kearns et al., 2003; Woo, 2004). In addition, maturation occurs at variable rates that implore the need for age- appropriate dose regimens for many drugs used in the neonatal and infancy period.

There are two types of metabolic occurrences – Phase I and Phase II reactions. Phase I enzymes, such as cytochrome P450 enzymes, are responsible for reactions like oxidation, reduction and hydroxylation that result in medication degradation. It is believed that by the age of 3, the various components necessary for Phase I reactions have reached adult levels. Phase II enzymes are responsible for conjugation reactions or the synthesis of water- soluble compounds that aid in renal or biliary elimination (Suggs, 2000; Woo, 2004). Phase II reactions are estimated to reach adult capacity by 3 to 4 years of age. Currently, the Phase I enzymes have been much better studied in the pediatric population than Phase II enzymes. However, as research continues, the knowledge base is ever expanding about pediatric drug metabolism.

Excretion. Elimination of drugs occurs primarily in the kidneys through filtration or active tubular secretion (Suggs, 2000). At birth, renal excretion is reduced due to a lower glomerular filtration rate (GFR), decreased renal blood flow, and decreased tubular function. By 8-12 months of age adult values are typically reached (Kearns et al., 2003). It is important that dosages and dosing intervals are adjusted to account for these differences in neonates and infants. It is particularly important to be aware of medication half-lives because in infants and neonates the half life can be prolonged with a reduced GFR (Suggs, 2000).

Dosing in children. Medications must always be prescribed taking the individual’s circumstances into consideration, e.g. appropriate medication for the diagnosis, appropriate formulation, and appropriate route of administration. In children, it is particularly important to ensure that the child’s individual criteria are taken into account when selecting the appropriate dose. These criteria include age of the child, the level of maturation of organ development, the particular disease or condition requiring treatment, comorbid conditions being treated, other medications being used, and the potential for drug-drug interactions. Dosing in children is most often based upon the body weight, in a mg/kg dose, but all individual criteria should be considered in pediatric prescribing. Additionally, a pediatric dose should never exceed a normal adult dose, even in cases of obesity where a body weight calculation may produce such a result (Adcock, 2006).

The major physiologic differences that exist between children and adults are most significant during the neonatal and infancy periods. Dosing during the neonatal period is based upon body weight, gestational or postnatal age, and the level of organ maturation that subsequently affects the renal or hepatic function. Throughout infancy it is important to consider the effects of medications on the immature kidneys and liver. The slower rates of metabolic processes of the liver in infancy affects the metabolic drug degradation capabilities of the liver and results in a prolonged half-life of medication in the system. Thus, it is extremely important to prevent toxicity through the use of lower doses and longer dosing intervals. It is also important to remember that medications t\hat are renally excreted must be given at lower doses because of the decreased glomerular filtration rate during the neonatal period until about 6 to 12 months of age (Adcock, 2006).

When prescribing to infants and children it is very important to consider the half-life of a drug, or the amount of time that it takes for plasma concentration of the drug to decrease by 50%. This is especially important because the half-life influences the loading dose and dosing interval. In neonates and infants, medications that have a long half-life may take a longer period of time than is desirable to reach a steady state concentration due to decreased drug degradation capability of the liver. Therefore, a loading dose is often required to get drug levels more quickly to a therapeutic level. Dosing intervals is also influenced by the half-life of a medication which is heavily influenced by the hepatic and renal clearance. In infants and children some medications may need to be dosed more or less frequently than in adults due to these variations in clearance (Adcock, 2006).

Summary

Prescribing medications to children is one of the most complex and potentially dangerous functions pediatric advanced practice nurses perform. Over a quarter of the medications in the Harriet Lane Handbook formulary of commonly prescribed medications in children, have no FDA approval for use in children. Many other medications have limited official FDA approved indications and are routinely prescribed “off-label.” Without official, scientifically controlled, human studies in children of varying ages, medications are often prescribed for children based on their therapeutic indications, safety, and efficacy in adults. This “offlabel” use of medications must adhere to “community standards of care” or the provider runs the risk of litigation if untoward effects occur. The use of well respected and current pharmacology resource tools, e.g. the PDR, the Harriet Lane Handbook, and Micromedex is one way to establish the “community standard of care.” The use of multiple resources is recommended because not all information needed to prescribe a variety of medications safely is found in one source. As more practice sites have internet access resource tools such as Micromedex, that are updated more frequently than textbooks, these may be found to be more accurate and complete.

Pediatric nurses prescribing medications to children must recognize the pharmacokinetics of the drugs prescribed and the physiologic stage of development of the child. This is most critical when prescribing to neonates and infants. Agespecific dosing recommendations in pediatric pharmacology resources must be utilized to establish dosing guidelines but then the individual condition of the child and other medications being used must be factored into the calculation. Consultation with a physician is recommended when prescribing medications not frequently used or when prescribing to a child with chronic health conditions or physiological alterations in development of organ systems that may alter the absorption, distribution, metabolism, or excretion of medication.

Pediatric nurses must also serve as advocates for responsible and ethical pediatric drug studies. The exclusivity extension provision of the “Best Pharmaceuticals Act for Children” will be up for renewal in 2007. This Act has helped to encourage pediatric studies for both new and old medications through the 6-month extension of patent for pharmaceutical companies to test new medications and authorization of the NIH to conduct drug studies in older medications that are no longer patented. It behooves pediatric nurses to actively campaign for its passage since testing of drugs helps to ensure the safety of drug administration in children.

The Primary Care Approachessection focuses on physical and developmental assessment and other topics specific to children and their families. If you are interested in author guidelines and/or assistance, contact Patricia L. Jackson Allen at pat.jacksonallen@yale.edu.

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Patricia L. Jackson Allen, MS, RN, PNP, FAAN

Emily Novak, MSN, RN, PNP, was a graduate student at Yale University School of Nursing, New Haven, CT, at the time this article was submitted.

Patricia Jackson Allen, MS, RN, PNP, FAAN, is Professor and Director, Pediatric Nurse Practitioner Specialty, Yale University School of Nursing, New Haven, CT. She is also a member of the Pediatric Nursing Editorial Board.

Copyright Anthony J. Jannetti, Inc. Jan/Feb 2007

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