Common Childhood Illnesses: Considerations for the Pharmacy Technician
Pediatric patients are especially vulnerable to medication errors and drug product safety. In addition, they have unique physiological compositions that require special considerations related to medication choice and dose. Interventions in community and hospital pharmacy practice settings can reduce the incidence of inappropriate or incorrect prescribing practices for pediatric patients. Because pharmacy technicians are involved in the dispensing process of medications for pediatric patients, they should understand unique characteristics of pediatric patients, as well as common illnesses and medications recommended for use in this population, in order to improve medication safety and patient care.
BODY COMPOSITION AND PHYSIOLOGICAL CHARACTERISTICS OF PEDIATRIC PATIENTS
Pediatric patients are not just small adults. There are significant differences between pediatric and adult patients in terms of drug efficacy, toxicity, and pharmacokinetics, which is the study of drug absorption, distribution, metabolism, and excretion. 1,2 Pediatric patients are defined as those who are under 18 years of age; they can be further classified according to the following age groupings: those who are born before 37 weeks of gestational age are premature; newborns between 1 day and 1 month of age are neonates; patients aged 1 month to 1 year are infants; patients between 1 and 11 years are children; and patients between 12 and 16 years are adolescents.1 Although the same general principles of pharmacotherapy apply to pediatric and adult patients, differences in body composition add to the complexities involved with drug dosing in the pediatric population.3
Children comprise a smaller percentage of the population than adults, and, generally, children tend to be healthier than adults. Pediatric-specific drug product development tends to be limited and only about 20% of approved drugs are labeled for pediatric use. Still, many drugs that are approved by the United States (U.S.) Food and Drug Administration (FDA) for adults are used in the pediatric population, despite no indication for use in these younger patients.1,4-6 In part, this can be attributed to the lack of efficacy, safety, pharmacokinetic, and pharmacodynamic data in this population.1,4,7 (Pharmacodynamics is the relationship between drug concentration and the overall pharmacologic response.) Ethical and practical limitations have prevented drug studies from including children, so much of the available data regarding medication use in pediatric patients are based on adult studies and trial and error in the pediatric population.8,9 In the past, a lack of understanding regarding the features and characteristics of pediatric patients led to disasters such as gray baby syndrome from chloramphenicol, phocomelia from thalidomide, and kernicterus from sulfonamide therapy.1
Many pediatric medications are dosed according to body weight. Alternatively, some agents are dosed by body surface area (BSA).1 However, among pediatric patients, weight and BSA vary considerably9 and optimal dosages are often difficult to determine. Doses for pediatric patients cannot be extrapolated from adult drug regimens that are based on body weight or BSA because of the notable differences in organ function and body composition.1,8,11 Generally, the highest recommended individual or daily dose for a pediatric patient should not exceed the amount of drug indicated in the adult population.1 As mentioned previously, the pharmacokinetics of a drug are predicted through absorption, distribution, metabolism, and elimination. These parameters must be considered in order to achieve consistent, safe, and effective therapeutic exposure to drugs; however, these factors change rapidly in pediatric patients, further complicating drug dosing.8
If a drug is administered orally, its absorption into systemic circulation is determined by active diffusion, pH-dependent passive diffusion, and gastric emptying time.1,7,8,12 The functionality of these processes differs depending on the stage of the human life cycle. For example, the gastric pH in a full-term neonate ranges from 6 to 8 at birth, but it declines to between 1 and 3 within 24 hours.1,8,12 However, in premature neonates, the pH remains elevated because of undeveloped acid secretion.1 As a result, acid-sensitive drugs, such as penicillin, exhibit higher serum concentrations in premature neonates.1 Also, gastric emptying time is decelerated in pediatric patients, leading to prolonged drug contact with the gastric mucosa, which can result in higher drug levels than those observed in older patients.1,8 According to studies involving drugs and nutrients, both passive and active transport in the gastrointestinal tract are believed to be fully developed by approximately 4 months after birth.1
Additionally, the rate and extent of drug absorption from the intramuscular (IM) route of administration is impacted by stages in the human life cycle. Differences in muscle mass, perfusion, stability, and muscular contractions in premature infants compared with older patients and adults can influence drug absorption after IM administration, although these factors are difficult to predict and measure.1 The IM administration of drugs also carries the risk of nerve and muscle damage; therefore, this method of drug delivery is rarely used in very young patients. Also, percutaneous drug absorption is affected by properties of both muscle and skin. Neonates have an underdeveloped epidermal barrier and increased skin hydration compared with older infants and children, making them prone to toxicity from topically administered medications because of enhanced drug absorption.1,13
Drug distribution is determined by the chemical properties of a drug, which are constant. However, the physiological influences of a drug vary among age groups.1 For example, drug distribution is affected by organ maturity, blood perfusion, extravascular water content, body fat composition, tissue permeation, total body water, protein binding in plasma, and underlying pathological conditions.1,7,8 As patients age, total body water decreases and total body fat increases, which collectively have a substantial impact on drug distribution.8 In adults, total body water accounts for 60% of body weight; in full-term neonates, 78%; and in premature neonates, 85%.1 Extracellular fluid accounts for 19% of body weight in adults; 25% in 1-year-old children; 35% in 4- to 6-month-old infants; and 50% in premature neonates. Because younger patients have a substantially lower percentage of body fat than those patients who are older, lipid-soluble drugs (those that readily penetrate the membranes of cells) are less widely distributed. As a result, these differences in drug distribution must be taken into consideration when establishing dosing regimens in pediatric patients. Notably, by approximately 3 years of age, body water and body fat levels in pediatric patients are nearly the same as those in adults.8
Plasma protein concentrations increase with age.1,7,8 As a result, select drugs exhibit an increased volume of distribution in pediatric patients compared with adults, necessitating larger loading doses to achieve therapeutic serum concentrations of drug.1 Also, free or unbound drug can cause toxic effects if appropriate drug monitoring parameters are not followed. For example, some drugs, including sulfisoxazole, dicloxacillin, and ceftriaxone, displace bilirubin from protein binding sites on albumin and other proteins, which raises the concentration of bilirubin in the blood. This effect can lead to a rare neurological condition called kernicterus.1,8,14
Most drug metabolism occurs in the liver; however, it may also take place in the blood, gastrointestinal wall, kidney, lung, and skin.8 In general, drug metabolism is slower in infants compared with older children and adults because of several important differences related to drug metabolic pathways. For example, the sulfation pathway is well-developed in infants, but the glucuronidation and oxidation pathways are underdeveloped. Specifically, the glucuronidation pathway may take up to 1 year to fully develop, while the enzymes involved in oxidation show variable patterns of expression until adulthood.1,8 Some of these variations are due to genetics. For instance, recent genetic studies have demonstrated that some patients possess multiple copies of oxidative enzymes that can lead to ultrarapid metabolism of certain drugs, including codeine, and this accelerated metabolic process has been linked to significant morbidity and mortality. For this reason, among others, codeine is recommended to be used cautiously in children15; in fact, the FDA unveiled several label changes in an effort to better protect pediatric patients and indicated that codeine should not be used in anyone younger than 18 years old.16
Many drugs and metabolites are eliminated from the body by the kidneys. (In medical literature, the term renal is often used interchangeably with the term kidney.) Glomerular filtration, tubular secretion, and tubular reabsorption influence the renal excretion of drugs. Importantly, these processes develop at different rates and reach maturity at approximately 1 year after birth. For example, the estimated glomerular filtration rate (eGFR) is 0.6 to 0.8 mL/min/1.73 m2 in premature neonates and 2 to 4 mL/min/1.73 m2 in full-term neonates. (Adults and pediatric patients older than 3 years of age have an eGFR of 90 to 120 mL/min/1.73 m2.) Therefore, premature neonates require lower doses of drugs that undergo renal elimination.1,8 For example, tobramycin, gentamicin, and amikacin are aminoglycoside antibiotics that are cleared renally from the body; each drug can cause serious kidney damage or hearing loss if accumulation occurs in the body; therefore, drug doses must be adjusted according to renal function.17 In addition to differences in absorption, distribution, metabolism, and excretion, drug formulation and the presence of excipients influence the selection of products that are used in pediatric populations.18-21 For example, benzyl alcohol is a common antibacterial agent that is used in a variety of product formulations. However, the accumulation of benzyl alcohol can have toxic effects in neonates, which can lead to a potentially fatal complication known as gasping syndrome.22
Pathophysiological changes that accompany childhood diseases or conditions also influence drug therapy. For example, obesity affects the pharmacokinetics of many drugs, which is a significant concern because one-third of children and adolescents are overweight or obese.1,8,23 Obesity increases the risk for comorbid conditions, such as high blood pressure, high cholesterol, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary disorder, cholecystitis, gastroesophageal reflux disease, and obstructive sleep apnea. Further, obese children have higher body fat mass, higher bone mineral content,24,25 higher total body water, lower lean muscle mass, increased organ mass, greater cardiac output, higher eGFR, and higher serum creatinine concentrations than normal weight children.1 As a result, obese children have a higher volume of distribution for lipophilic drugs and a lower volume of distribution for hydrophilic drugs. Several methods for calculating lean body mass, ideal body weight, and modifying drug doses in obese pediatric patients are available; however, they remain controversial.24
MEDICATION SAFETY IN PEDIATRIC PATIENTS
All healthcare professionals have a responsibility to ensure the safe use of medications in all patients. Pediatric patients are among the most vulnerable to medication errors, so it is incumbent on healthcare professionals to identify and understand high-risk areas in the medication-use process and to mitigate the risks of errors before they reach these patients.1,10,26,27 Medication errors may occur in as many as 10% of pediatric patients on medical wards—and the younger the patient is, the greater the risk of a harmful error.6,7,28 Medication errors in pediatric patients are 3 times as likely to cause harm compared with adult patients.29,30
Medication adherence and compliance are complex issues for pediatric patients. They are influenced by poor communication between the physician and patient or parent, lack of appreciation of disease severity by the patient or parent, lack of interest by the patient, fear of side effects, inconvenient dosing schedules, and unpalatability of drug products. Additionally, nearly half of all caregivers administer complementary and alternative therapies to children.1 Such treatments, including herbs, vitamins, plant-based products, and homeopathic agents, may interact with traditional medications; however, caregivers may not realize the potential dangers of these medicines. Healthcare professionals, including pharmacy technicians, must be vigilant to ask about complementary and alternative medicine use in pediatric patients. If these types of medicines are identified during patient or caregiver discussions, it is important that pharmacists and pharmacy technicians add these medicines into the computer profile for each patient.1,31
Virtually every pharmacist and pharmacy technician works with pediatric patients in some capacity. Still, pediatric prescriptions can be a source of anxiety for pharmacy personnel, which may be related to a lack of education in pediatric pharmacotherapy.10,32 Thankfully, medication safety and pediatric care has improved dramatically since disasters of the past, partly because of the improvements in education and drug regulation. In the last 2 decades, regulatory and legal efforts to address pediatric medication needs have afforded better access to safe and effective drugs around the world. Legislation and regulation have been expanded to allow—and encourage—the inclusion of pediatric patients in drug studies. Specifically, as part of the Food and Drug Administration Modernization Act (FDAMA) of 1997, Congress enacted a law that provided marketing incentives to drug manufacturers who conduct studies in pediatric patients. This law provided 6 months of marketing exclusivity in return for conducting drug evaluations in the pediatric population, which equated to large financial gains (for drug manufacturers) in most instances.33
The FDA also enacted the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), which require the pharmaceutical industry to conduct studies and create labeling specific to drugs used in pediatric patients.1,8,34-36 The BPCA was enacted in 2002 after pediatric exclusivity provisions in the FDAMA expired. In addition to renewing the exclusivity and patent extension incentives, the BPCA allows the FDA to refer drugs to another agency for pediatric study if the manufacturer chooses not to pursue pediatric drug trials. The FDA can actively solicit new sponsors to study drugs if pediatric data are needed beyond those provided by the manufacturer. Notably, the study of generic drugs in the pediatric population is usually conducted by the National Institutes of Health, considering generic drug manufacturers have little financial incentive to study these drugs further.8
The PREA authorized the FDA to require drug manufacturers to conduct pediatric studies if the potential for use in pediatric patients exists.36 Through expanded legislation, many pediatric studies have been conducted, which has led to new warnings and safety data, dosing and standardization instructions, and drug design. As a result, healthcare providers can confidently prescribe drugs in a vulnerable population. The FDA maintains a searchable database of pediatric labeling obtained from manufacturers’ studies in the New Pediatric Labeling Information Database.37
Medication errors in pediatric patients are a frequent and recurring problem. In the last decade, more than 200,000 out-of-hospital medication errors in the U.S. were reported to poison control centers each year, which equates to 1 medication error every 8 minutes. Nearly one-third of these errors involved children under 6 years of age, with the youngest patients most likely to be involved in an error. For example, infants less than 1 year of age accounted for 25.2% of medication errors while 5-year-old children accounted for 9.7%.31 During this decade-long study, the overall rate and number of errors did not fluctuate significantly; however, the types of medications involved in these errors did change. These deviations are likely a result of actions taken by the FDA, drug manufacturers, academic organizations, and professional groups, which have recommended against the use of cough and cold products in very young children.31
Cough and cold products contain various combinations of antihistamines, decongestants, antitussives, and expectorants; many products also contain acetaminophen as a pain reliever and fever reducer.11,38 The marketing of over-the-counter (OTC) cough and cold products continues to be a source of confusion for caregivers. For example, products with similar ingredients are marketed for different indications, while products with different ingredients are marketed for the same indication.11 Further, decongestants have been linked to cardiac arrhythmias and other cardiovascular events; antihistamines to hallucinations; and antitussives to depressed levels of consciousness and encephalopathy.11,38 The risk of medication errors with cough and cold preparations may be higher in young children because of the greater number of colds they experience each year compared with those patients who are older.39 Also, the risk of a medication error is increased in the pediatric population when administered under the following circumstances: (1) when a medication is used for sedation, (2) when a medication is used in a daycare setting, (3) when 2 medications with the same active ingredients are used, (4) when a measuring device is not used, (5) when a product is misidentified, and (6) when a product that is intended for adult use is administered to a child.40
There is little evidence to support the effectiveness of cough and cold products in young children, but caregivers continue to administer them.11,39,40 In 1997, the American Academy of Pediatrics (AAP) issued a policy statement noting that the “indication for [the use of cough and cold preparations has] not been established.” And, in 2006, the American College of Chest Physicians reported that the “literature regarding OTC cough medications does not support the efficacy of such products in the pediatric age group.”11 This lack of safety and efficacy data prompted the FDA to issue a public health advisory in 2008 that recommended against the use of these drugs in children younger than 2 years of age.1,38 As a result, drug manufacturers countered by voluntarily changing the product labeling for certain cough and cold medications to read: “do not use in children under 4 years of age.”1
While errors with cough and cold medications have decreased significantly since 2002,41 data suggest the number and rate of errors with other medications, including nutraceuticals, cardiovascular drugs, analgesics, anticonvulsants, antihistamines, and muscle relaxants, have risen during the same time period. Notably, among medications errors reported to U.S. poison control centers from 2002 through 2012 (the most recent data available), analgesics were identified as the most common drug class associated with errors in children (25.2%), followed by cough and cold products (24.6%), antihistamines (15%), and antimicrobial agents (11.8%).31 Over the course of the study period, 25 patients died as a result of a medication-related error. Of these deaths, 40% were attributed to analgesics and 20% were attributed to cough and cold preparations. Further, most out-of-hospital errors (81.9%) in pediatric patients involve liquid preparations. Common causes of errors included accidentally taking or being given the medication twice, incorrect dosing, confusing units of measure, and giving or taking the wrong medication. In response to increased measurement errors, manufacturers of OTC liquid pediatric acetaminophen products began voluntarily converting all formulations to one concentration in 2011. Prior to this date, products were available in a variety of concentrations for different age groups.31
Additionally, pediatric patients are at increased risk for medication errors compared with adults because doses are based on factors such as age, weight, and BSA. Dosing errors are reported to be the most common type of error during the medication-use process in pediatric patients.26-28 Pharmacists and technicians should always verify a pediatric patient’s weight and, in most cases, convert the weight from pounds to kilograms. This conversion is important because dosing recommendations that appear in product package inserts and pediatric references are usually based on kilograms of body weight—not pounds. Also, pharmacy personnel should calculate (or recalculate) the dose provided on the prescription, verify it against a pediatric-specific drug reference, and have another individual double check the quantities and concentrations of all drugs included in the prescription.10
One common type of a dose miscalculation is a 10-fold dosing error.10,28 A 10-fold error is one that results in a medication dose that is 10-times greater than or one-tenth of the intended dose. The misuse of decimals is a common contributor to 10-fold errors. For example, a dose written as “.1 mg” might be interpreted as “1 mg” if the decimal point is ignored or not seen. This type of error may lead to an underdose or an overdose of a particular medication, which, in turn, leads to decreased efficacy or toxicity, respectively. Ten-fold dosing errors are especially dangerous in the pediatric population because of myriad variations that exist, including age, weight, drug formulations, drug dilutions, pharmacokinetics, pharmacodynamics, off-label use, and multiple barriers to effective communication. Notably, in a hospital-based analysis, morphine and related opioids were among the most commonly reported drugs associated with 10-fold dosing errors. Intravenous formulations, paper ordering systems, and drug-delivery pumps were identified as offenders in many of these cases.28 Moreover, other common types of medication errors that occur in pediatric patients include inappropriate medication for the condition being treated, incorrect frequency of administration, wrong route of administration, failure to recognize drug interactions, lack of monitoring, and inadequate communication between the physician and other members of the healthcare team.26
Strategies that reduce medication errors, such as dosing standardization and policies to guide medication-use processes, can minimize negative outcomes for pediatric patients.28,29 Specifically, dosing standardization removes the risk of miscalculation because doses are based on therapeutic ranges within weight-based dosing categories. For instance, a decrease in the overall error rate among pediatric patients was observed in a hospital-based study of antibiotic dosing standardization.29 Computerized order entry systems have also had a positive impact on pediatric medication errors, partly from the assistance with dosage calculations and clinical decision support.42 The AAP recommends that healthcare providers adopt electronic prescribing systems, specifically, systems that have pediatric-specific functions.43,44
In addition to identifying and preventing system-based errors, the human element that contributes to medication errors must be identified. Human errors may involve lapses in judgment or knowledge, ignoring practice site policies and procedures for patient safety, or bypassing alerts and safeguards that have been established to maintain patient safety. Importantly, vigilance and training may not be enough to prevent all errors in pediatric patients. Instead, a culture of safety should be established in healthcare, and system-wide approaches should be implemented to enhance the reliability of any system, process, or individual who provides pediatric care and support.7
Patient and caregiver education cannot be ignored as an element of improved medication safety. Healthcare providers should educate parents about the appropriate use of medications to treat pain, fever, coughs, and colds. Efforts that have achieved success in increasing the safety of cough and cold products in children should be duplicated with other classes of drugs.31 Parents should also be educated about the proper use of measuring devices,10,26 the need to avoid sharing medications between siblings,24 how to read a drug label,38 and how to monitor for signs of an adverse drug reaction.10
COMMON CHILDHOOD ILLNESSES
Knowledge of common illnesses and conditions that affect pediatric patients is imperative for all pharmacy staff members. Some illnesses affect children disproportionately compared with adults, while other conditions offer special considerations for pediatric patients. Common illnesses and treatment categories that pharmacy technicians often encounter are discussed here.
Fever and pain
Fever is a common reason for medical office and emergency room visits among children. A clinically significant fever is defined as a body temperature that is higher than the upper limit of a normal core body temperature (100.4°F or 38°C). Fever is, itself, not an illness, but rather an infection-fighting response45: it is generated by the body in response to a pyrogen (a fever-producing substance) and is regulated by the hypothalamus in the brain. Most fevers are a result of microbial infections, but fevers may be caused by a drug reaction, dehydration, metabolic disorders, central nervous system inflammation, or tissue damage; however, the magnitude of the change in body temperature is not correlated to the cause of the fever. Most fevers are self-limiting and, in the absence of a serious underlying cause, treatment is aimed at reducing discomfort.45,46 Serious complications related to fevers are uncommon, but harmful effects may occur when the core body temperature reaches 106°F (41.1°C) or higher.47
Arguments against the treatment of fever include the generally benign and self-limiting course of the condition, the elimination of a prognostic or diagnostic sign, and the therapeutic effects of the fever, considering it is the body’s way of enhancing host defense systems and eliminating an infection-causing organism. Still, fever increases oxygen consumption by the body, increases carbon dioxide production, and increases cardiac output, which manifest as the fatigue-like symptoms that patients experience during the course of a fever. Nonpharmacologic approaches for the treatment of fever include wearing light clothing, removing blankets, lowering the ambient temperature, and drinking fluids to mitigate water loss that occurs through evaporation and respiration.46
The most common antipyretic agents for the treatment of fever include acetaminophen, aspirin, and ibuprofen, which are all available without a prescription.45,46 Aspirin should not be used in children under 15 years of age because of the known risk of Reye’s syndrome, a rare condition that causes swelling of the liver and brain. Doses of acetaminophen and ibuprofen for use in pediatric patients should be based on body weight—not age.45 Some evidence suggests that acetaminophen and ibuprofen may be administered together or alternated every 4 hours, but little data exist that show a benefit in patient outcomes with this method and this practice increases the risk for caregiver confusion and possible overdose.48-50 Further, this treatment strategy increases the risk of medication errors and adverse events.46,49 Caregivers of pediatric patients with fever should be advised to only give single-ingredient fever-reducing products, use the lowest possible dose, and measure preparations using accurate devices. If a fever persists after 3 days of antipyretic treatment or if the fever worsens with treatment, caregivers should be instructed to seek medical attention.46
Children also commonly experience headache and muscle pain. As with fever, the underlying cause of the pain should be identified and treated appropriately, but analgesics may be administered to decrease discomfort. Antipyretic agents available for the treatment of fever (e.g., acetaminophen and ibuprofen) are also analgesics, which are commonly used for the treatment of mild-to-moderate pain. It is important to remember that acetaminophen is an effective pain reliever and fever reducer, but it does not possess anti-inflammatory activity.51,52
Common cold and cough
The common cold is a self-limiting viral infection of the upper respiratory tract that is most often caused by a rhinovirus.53 The common cold cannot be cured and should not be treated with antibiotics.53,54 In most circumstances, the cold will resolve without intervention in approximately 1 week.38 The symptoms of the common cold include sore throat, nasal congestion, runny nose, sneezing, and cough. Patients may also experience chills, headache, pain, achiness, or low-grade fever.53,54 Caregivers often try to treat symptoms of the common cold with antihistamines, decongestants, cough suppressants, and expectorants; however, these agents lack safety and efficacy data in select pediatric populations and offer a high risk of medication errors.1,31 To ease the discomfort associated with a cold, mucus can be suctioned from the nasal passages with a bulb syringe38 or treated with saline irrigation.53,55 These simple and benign therapies decrease the need for other cough and cold medications, including antihistamines and decongestants.38,55 Acetaminophen or ibuprofen may lessen fever and pain,36 but rest and hydration are considered to be the most beneficial treatment options for those suffering from the common cold.53,54
Cough is one of the most common symptoms for which people seek medical care.56,57 Cough is an important defensive reflex of the respiratory system that attempts to remove mucus, cellular debris, or foreign bodies from the lower respiratory system; however, cough can irritate the throat and chest and may, ultimately, interfere with school and sleep. Further, coughs are classified as productive or nonproductive. A productive cough (i.e., wet cough) expels secretions from the airways. A nonproductive cough (i.e., dry cough) serves no physiological purpose and is usually the result of a viral respiratory illness or atypical bacterial infection.57 Antitussive agents, also called cough suppressants, are intended to eliminate coughs and are widely considered to be the treatment of choice for those considered nonproductive. Expectorants alter the consistency of mucus and increase the volume of sputum that is expelled with each cough. Expectorants are appropriate treatments for irritating nonproductive coughs and for productive coughs that expel thick secretions.58 Dextromethorphan is the most common OTC cough suppressant, and guaifenesin is the most common expectorant. Hydration and humidifiers can also soothe airways and decrease cough.58 In addition, honey59-61 may also relieve cough symptoms in children over the age of 12 months; importantly, infants under 12 months of age should not consume honey because of the risk of botulism.62,63 Honey may offer little benefit compared with placebo (i.e., no active drug), but because of the low cost and nontoxic nature of these syrups, caregivers may prefer trying these remedies rather than offering no treatment.56,59
Pediatric patients are exposed to many infectious diseases. Antibiotic therapy should be used judiciously in all patients, and therapy should be directed toward the specific disease-causing agent. However, some classes of antibiotics have unique cautionary measures that must be considered in every pediatric patient.1,13 For example, fluoroquinolones (e.g., ciprofloxacin and levofloxacin) are generally not recommended for use in pediatric patients because of reports suggesting the development of arthropathy and lesions in the cartilage of weight-bearing joints. However, ciprofloxacin is recommended for patients under 18 years of age for inhalation anthrax postexposure or for the treatment of complicated urinary tract infections and pyelonephritis caused by Escherichia coli; in these circumstances, the benefits of therapy outweigh the risks.1
Acute otitis media is a type of upper respiratory tract infection that causes inflammation of the middle ear. Its diagnosis depends on symptomatology, which includes fever, pain, irritability, and the presence of fluid in the middle ear. It is most commonly caused by Streptococcus pneumoniae, but it can also be caused by Haemophilus influenzae, Moraxella catarrhalis, and viruses. Otitis media is most common in infants and children. Risk factors for bacterial otitis media include daycare attendance, recent antibiotic exposure, age less than 2 years, and frequent bouts of ear infections. Young children are more vulnerable to otitis media than adults because of differences related to the anatomy of the eustachian tube, a tube that links the nasopharynx to the middle ear. Specifically, the eustachian tube in children is shorter and more horizontal, which facilitates the entry of bacteria into the middle ear.64-65
The treatment of otitis media is controversial. The overprescribing of antimicrobial agents for otitis media has contributed to antimicrobial resistance, and, therefore, many practitioners advise a plan of additional observation, nonpharmacologic treatment, or delayed antimicrobial therapy. Observation without immediate intervention is appropriate for children older than 2 years who have acute uncomplicated otitis media and non-severe illness, as long as follow-up care is available.65 Without antibacterial treatment, symptoms of otitis media improve within 24 hours in 60% of children; symptoms improve within 3 days in 80% of children. Serious complications related to otitis media are rare.66
The AAP recommends antibiotic therapy for patients between 6 months and 2 years of age in the following situations: acute otitis media with otorrhea (ear drainage), unilateral or bilateral acute otitis media with severe symptoms, and bilateral acute otitis media without otorrhea. In addition, antimicrobial therapy may be initiated in this age group when patients have unilateral acute otitis media (and no otorrhea) with a plan to initiate therapy within 48 to 72 hours of symptom onset if the child worsens or fails to improve. For children older than 2 years of age, antibiotic therapy should be initiated immediately in cases of acute otitis media with otorrhea and unilateral or bilateral acute otitis media with severe symptoms.64 Antibiotic treatment is also recommended for children of any age with a temperature greater than 102.2°F (39°C), who are toxic looking, have had ear pain for more than 48 hours, have bilateral otitis media or otorrhea, have craniofacial abnormalities, or are immunocompromised.65
Amoxicillin 80 to 90 mg/kg/day divided in 2 doses is the drug regimen of choice for children with acute otitis media who are not allergic to penicillin.67 If severe symptoms are present, such as severe pain or a temperature greater than 102.2°F (39°C), amoxicillin-clavulanate may be administered as first-line therapy. In patients with a penicillin allergy, cefdinir, cefuroxime, cefpodoxime, ceftriaxone, azithromycin, or clarithromycin may be considered.64 However, caution should be exercised when substituting a cephalosporin for an amoxicillin-containing product, as the potential for cross-sensitivity may be as high as 10.9%.68 Azithromycin and clarithromycin have limited efficacy against common bacterial causes of otitis media, but they may be the best options for patients who cannot tolerate amoxicillin or cephalosporins. In some cases, a 5- to 7-day course of antibiotics may be effective, but other patients may require longer courses of antibiotics, up to 10 to 14 days.64
Acetaminophen or ibuprofen can be used to decrease pain and fever associated with otitis media. Decongestants, antihistamines, and other cough and cold products are not effective for otitis media. Also, antibiotic therapy is not effective for viral otitis media.64,66
The following patient case illustrates a scenario that pharmacy technicians may encounter in a routine workday.
PHARMACY PRACTICE CASE
A mother enters a community pharmacy and presents a prescription for amoxicillin 400 mg/5 mL with the following instructions: Take 1 teaspoonful (400 mg) of amoxicillin twice daily for 10 days. The prescription is for her daughter who has acute otitis media. The pharmacy technician confirms the child’s birth date and weight: she is 18 months old and weighs 20 pounds (lbs).
- What is your next step?
- A. Verify the child’s medication allergies
B. Verify the dose of amoxicillin
C. Verify if the patient is taking any other medications
D. All of the above
The correct answer is D. To ensure safe and effective medication use in pediatric patients, pharmacy technicians should verify allergies, comorbid conditions, other medications, and patient weight every time a prescription is presented. Any missing or inaccurate information can be addressed at this time, rather than later in the medication-use process. Additionally, whenever a drug is dosed by weight, technicians and pharmacists should recalculate the dose to verify its accuracy.
The pharmacy technician confirms the child’s medical history and allergies with the mother. Next, the technician calculates the dose to ensure the prescribed dose is correct. Since the mother offered the patient’s weight in pounds, it must be converted to kilograms (kg): 20 lbs x 1 kg/2.2 lbs = 9.09 kg. The recommended dose of amoxicillin for acute otitis media is 80 to 90 mg/kg/day divided in 2 doses. Therefore, 800 mg (the total daily dose for this patient—1 teaspoonful twice daily) ÷ 9.09 kg = 88 mg/kg/day; the prescribed dose is, therefore, within the recommended dosing range. Importantly, the pharmacist must confirm the pharmacy technician’s calculations, as well as dosing instructions before the drug is dispensed.
When the mother returns to the pharmacy to pick up her daughter’s medication, she places several boxes of pediatric cough and cold products on the counter and indicates that she hopes these products will help her daughter feel better. What information could you offer to the mother?
- A. Tell her not to give any medications to her child until the course of amoxicillin is completed
B. Tell her that not all cough and cold products are considered safe and effective in young patients and ask the pharmacist to counsel the patient on over-the-counter product selection
C. Tell her that she can administer any medication, except for aspirin, to her daughter
D. Tell her that combination products are best for young children due to the ease of dosing
The correct answer is B. Under most circumstances, pharmacy technicians are not allowed to counsel patients on over-the-counter drug selection, indication, or use. However, pharmacy technicians have a unique vantage of the medication-use process for many patients and their families, so technicians are well-poised to detect and identify actual and potential sources of error. Technicians should immediately bring concerns to the attention of the pharmacist, who can then determine the best course of action.
Asthma is one of the most common chronic conditions among pediatric patients, affecting more than 6 million children and adolescents in the U.S.69,70 It is a chronic inflammatory disease of the airways involving the lungs. There is no known cure or primary prevention for asthma. It can be caused by a respiratory infection, exposure to allergens, environmental factors, emotional responses, exercise, and drugs or preservatives. The presentation of asthma is unpredictable, but it is generally characterized by variable airflow obstruction resulting from inflammation and bronchial smooth muscle constriction.69 Asthma is generally a disease of exacerbation and remission, with many patients experiencing long symptom-free periods. When symptoms do occur, they usually include shortness of breath, chest tightness, coughing, wheezing, or a whistling sound when breathing.69,71 The type and frequency of treatment is determined by the regularity and severity of symptoms as well as the level of impairment.69
Asthma treatment is highly individualized because of the variability in responses to medications. Inhaled corticosteroids, such as beclomethasone, budesonide, fluticasone, and mometasone, are commonly used treatments for the airway inflammation related to asthma.71 Also, beta-2 adrenergic agonists, which relax smooth muscles of the airway, prevent or treat bronchial smooth muscle constriction. Long-acting beta-2 adrenergic agonists such as salmeterol or formoterol provide long-term control, while short-acting agents such as albuterol or levalbuterol are used as rescue, or quick-relief, medications to treat exacerbations. Patient and caregiver education are critical for optimizing treatment outcomes. All asthma treatment regimens should include an action plan to decrease exposure to triggers that worsen symptoms. A step-wise approach to treatment usually involves monotherapy or combination therapy with short- and long-acting beta-2 agonists; low- or medium-dose inhaled corticosteroids; leukotriene modifiers, such as montelukast; and/or oral corticosteroids. Several combination products are available by prescription that contain an inhaled corticosteroid and a long-acting beta-2 agonist, which simplify dosing and increase compliance (e.g., fluticasone/salmeterol and budesonide/formoterol).69
Attention deficit/hyperactivity disorder (ADHD)
ADHD is a neurodevelopmental disorder that affects nearly 10% of children between the ages of 4 and 17 years.72 Boys are 2 times as likely to be diagnosed with ADHD than girls.71 ADHD is thought to be caused by a combination of genetic and environmental factors, and it is characterized by difficulty paying attention, excessive activity, and impulsivity. While these behaviors seem normal for children, ADHD is characterized by excessive or inappropriate behaviors that interfere with daily functioning at home or school. Children may have difficulty with attention, activity, impulsivity, or any combination of these symptoms, which often change as children age.72-74 For 75% of children, symptoms of ADHD will persist into adolescence while approximately half will carry symptoms into adulthood.73
Nonpharmacologic interventions for ADHD include a healthy diet, education, and cognitive behavioral therapies (CBT). Psychostimulants, including methylphenidate or amphetamine salts, are considered the most effective pharmacologic treatment interventions for patients with ADHD.73 Further, ADHD may occur with other diseases or mental health conditions, which may influence treatment.73,74 Atomoxetine (a nonstimulant) is a norepinephrine reuptake inhibitor that is an effective therapy for patients with ADHD who have a history of substance abuse. However, this agent carries a black-box warning about the risk of suicidal ideation. Other nonstimulants, including guanfacine and clonidine, can be used to treat ADHD; however, they are generally less effective than psychostimulants when used as monotherapy. Often, nonstimulants are used as adjunctive therapies to control specific symptoms such as insomnia.72,73
Depression is common among pediatric patients.75,76 The prevalence is estimated to be 2.8% in children younger than in 13 years and 5.6% in children aged 13 to 18 years.77 It may occur as a single diagnosis or in combination with other physical or psychological conditions.78 Depression among children and adolescents is complex and associated with significant morbidity and mortality.79,80 Many organizations recommend screening for depression in pediatric primary care in order to facilitate early diagnosis and implementation of care. 81 Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, sertraline, and citalopram, are first-line treatment options for depression. However, this class of antidepressants carries an increased risk of suicidal thoughts and behaviors in pediatric patients.1,75,78,82 As a result, SSRI product labels carry a black-box warning highlighting the need for close monitoring when used in select populations.1 Tricyclic antidepressants, including imipramine and nortriptyline, are generally safe for use in pediatric patients, but SSRIs offer superior efficacy and tolerability compared with tricyclic agents.83,84 CBT may also improve treatment response when used in pediatric patients.75,78,79
THE FUTURE OF PEDIATRIC PHARMACOTHERAPY
Safe and effective medication use in pediatric patients is a global health priority. A comprehensive understanding of the physiological changes that affect drug pharmacokinetics is paramount for all healthcare professionals, including pharmacy technicians.8 Additionally, an understanding of the social factors that influence medication use in pediatric patients will encourage rational and judicious use of medications.10,24 Manufacturers should conduct pharmacokinetic and pharmacodynamic studies to determine appropriate drug concentrations and dosing levels for pediatric patients, in addition to safety and efficacy trials in this population.11 All healthcare providers should ensure the provision of evidence-based pharmacotherapy to all pediatric patients.1
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- Van den Anker J, Reed MD, Allegaert K, Kearns GL. Developmental changes in pharmacokinetics and pharmacodynamics. J Clin Pharmacol. 2018;58(Suppl 10):S10-25.
- Phan H, Pai VB, Nahata MC. Chapter 3: Pediatrics. In: Chisholm-Burns MA, Schwinghammer TL, Wells BG, et al. Pharmacotherapy Principles & Practice. 4th McGraw-Hill Education; 2016.
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- Ameer A, Dhillon S, Peters MJ, Ghaleb M. Systematic literature review of hospital medication administration errors in children. Integr Pharm Res Pract. 2015;4:153-65.
- Antonucci R, Porcella A. Preventing medication errors in neonatology: is it a dream? World J Clin Pediatr. 2014;3(3):37-44.
- Sage DP, Kulczar C, Roth W, et al. Persistent pharmacokinetic challenges to pediatric drug development. Front Genet. 2014;5:281.
- Rivera-Chaparro ND, Cohen Wolkowiez M, Greenberg RG. Dosing antibiotics in neonates: review of the pharmacokinetic data. Future Microbiol. 2017;12:1001-16.
- Benavides S, Huynh D, Morgan J, Briars L. Approach to the pediatric prescription in a community pharmacy. J Pediatr Pharmacol Ther. 2011;16(4):298-307.
- Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radar--pediatric cough and cold medications. N Engl J Med. 2007;357(23):2321-4.
- Nicolas JM, Bouzom F, Hugues C, Ungell AL. Oral dosing absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions. Biopharm Drug Dispos. 2017;38(3):209-30.
- Khattak AZ, Ross R, Ngo T, Shoemaker CT. A randomized controlled evaluation of absorption of silver with the use of silver alginate (Algidex) patches in very low birth weight (VLBW) infants with central lines. J Perinatol. 2010;30(5):337-42.
- Wadsorth SJ, Suh B. In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns. Antimicrob Agents Chemother.1988;32(10):1571-5.
- Chidambaran V, Sadhasivam S, Mahmoud M. Codein and opioid metabolism: implications and alternatives for pediatric pain management. Curr Opin Anaesthesiol. 2017;30(3):329-56.
- S. Food & Drug Administration. FDA Drug Safety Communication: FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm. Updated January 22, 2018. Accessed December 19, 2019.
- Le J, Bradley JS. Optimizing antibiotic drug therapy in pediatrics: current state and future needs. J Clin Pharmacol. 2018;58 Suppl 10:S108-22.
- Valeur KS, Holst H, Allegaert K. Excipients in neonatal medicinal products: never prescribed, commonly administered. Pharmaceut Med. 2018;32(4):251-8.
- Thabet Y, Klingmann V, Breitkreutz J. Drug formulations: standards and novel strategies for drug administration in pediatrics. J Clin Pharmacol. 2018;58(Suppl 10):S26-35.
- Valeur KS, Holst H, Allegaert K. Excipients in neonatal medicinal products: never prescribed, commonly administered. Pharmaceut Med.2018;32(4):251-8.
- Turner MA, Shah U. Why are excipients important to neonates? Curr Pharm Des. 2015;21(39):5680-7.
- Gershanik J, Boecler B, Ensley H, et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982;307:1384-8.
- Matson KL, Horton ER, Capino AC; Advocacy Committee for the Pediatric Phamacy Advocacy Group. J Pediatr Pharmacol Ther. 2017;22(1):81-3.
- Ross EL, Jorgensen J, DeWitt PE, et al. Comparison of 3 body size descriptors in critically ill obese children and adolescents: implications for medication dosing. J Pediatr Pharmacol Ther. 2014;19(2):103-10.
- Ameer B, Weintraub MA. Pediatric obesity: influence on drug dosing and therapeutics. J Clin Pharmacol. 2018;58 Suppl 10:S94-107.
- Mehndiratta S. Strategies to reduce medication errors in pediatric ambulatory settings. J Postgrad Med. 2012;58(1):47-53.
- Jember A, Hailu M, Messele A, et al. Proportion of medication error reporting and associated factors among nurses: a cross-sectional study.BMC Nurs.2018;17:9.
- Doherty C, McDonnell C. Tenfold medication errors: 5 years' experience at a university-affiliated pediatric hospital. 2012;129(5):916-24.
- Aseeri MA. The impact of a pediatric antibiotic standard dosing table on dosing errors. J Pediatr Pharmacol Ther. 2013;18(3):220-6.
- Cunningham KJ. Analysis of clinical interventions and the impact of pediatric pharmacists on medication error prevention in a teaching hospital. J Pediatr Pharmacol Ther. 2012;17(4):365-73.
- Smith MD, Spiller HA, Casavant MJ, et al. Out-of-hospital medication errors among young children in the United States, 2002-2012. 2014;134:867-76.
- Taylor D, Yuen S, Hunt L, Emond A. An interprofessional pediatric prescribing workshop. Am J Pharm Educ. 2012;76(6):111.
- S. Food & Drug Administration. FDA/CDER SBIA Chronicles: Patents and exclusivity. https://www.fda.gov/downloads/drugs/developmentapprovalprocess/smallbusinessassistance/ucm447307.pdf. Published May 19, 2015. Accessed December 19, 2019.
- S. Food & Drug Administration. Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. https://www.fda.gov/ScienceResearch/SpecialTopics/PediatricTherapeuticsResearch/ucm509707.htm. Updated March 22, 2018. Accessed December 19, 2019.
- S. Food & Drug Administration. Best Pharmaceuticals for Children Act and Pediatric Research Equity Act: July 2016 Status Report to Congress. https://www.fda.gov/downloads/scienceresearch/specialtopics/pediatrictherapeuticsresearch/ucm509815.pdf. Published July 2016. Accessed December 20, 2018.
- S. Food & Drug Administration. Pediatric Research Equity Act (PREA). https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm607938.htm. Updated November 7, 2019. Accessed December 19, 2019.
- S. Food & Drug Administration. New Pediatric Labeling Information Database. http://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=labelingdatabase. Updated October 22, 2019. Accessed December 19, 2019.
- S. Food & Drug Administration. When to give kids medicine for coughs and colds. https://www.fda.gov/consumers/consumer-updates/when-give-kids-medicine-coughs-and-colds. Updated July 18, 2017. Accessed December 19, 2019.
- Ryan T, Brewer M, Small L. Over-the-counter cough and cold medication use in young children. Pediatr Nurs. 2008;34(2):174-180, 184.
- Dart RC, Paul IM, Bond GR, et al. Pediatric fatalities associated with over the counter (nonprescription) cough and cold medications. Ann Emerg Med. 2009;53(4):411-7.
- Mazer-Amirshahi M, Reid N, van den Anker J, Litovitz T. Effect of cough and cold medication restriction and label changes on pediatric ingestions reported to United States poison centers. J Pediatr. 2013;163(5):1372-6.
- Benjamin L, Frush K, Shaw K, et al; American Academy of Pediatrics Committee on Pediatric Emergency Medicine; American College of Emergency Physicians Pediatric Emergency Medicine Committee; Emergency Nurses Association Pediatric Emergency Medicine Committee. Pediatric medication safety in the emergency department. 2018;141(3).
- Johnson KB, Lehmann CU; Council on Clinical Information Technology of the American Academy of Pediatrics. Electronic prescribing in pediatrics: toward safer and more effective medication management. 2013;131(4):e1350-e6.
- American Academy of Pediatrics Council on Clinical Information Technology Executive Committee, 2011-2012. Electronic prescribing in pediatrics: toward safer and more effective medication management. 2013;131(4):824-6.
- Chiappini E, Bortone B, Galli L, de Martino M. Guidelines for the symptomatic management of fever in children: systematic review of the literature and quality appraisal with AGREE II. BMJ Open. 2017;7(7):e015404.
- Feret BM. Fever. In: Krinsky DL, Berardi RR, Ferreri SP, et al, eds. Handbook of Nonprescription Drugs: An Interactive Approach to Self-care. 17th Washington, D.C.: American Pharmaceutical Association (APhA) Publications; 2011.
- Rosenfeld-Yehoshua N, Barkan S, Abu-Kishk I, et al. Hyperpyrexia and high fever as a predictor for serious bacterial infection (SBI) in children-a systematic review. Eur J Pediatr. 2018;177(3):337-44.
- Luo S, Ran M, Luo Q, et al. Alternating acetaminophen and ibuprofen ersus monotherapies in improvements of distress and reducing refractory fever in febrile children: a randomized controlled trial. Paediatr Drugs. 2017;19(5):479-86.
- Chung AM. An evaluation of community pharmacy recommendations regarding alternating antipyretics in children. J Am Pharm Assoc (2003). doi: 10.1016/j.japh.2018.06.015. [Epub ahead of print].
- Mistry N, Hudak A. Combined and alternating acetaminophen and ibuprofen therapy for febrile children. Paediatr Child Health. 2014;19(10):531-2.
- Chornomydz I, Boyarchuk O, Chornomydz A. Reye (Ray’s) syndrome: a problem everyone should remember. Georgian Med News. 2017;(272):110-8.
- National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Reyes-Syndrome-Information-Page. Updated March 27, 2019. Accessed December 19, 2019.
- Fashner J, Ericson K, Werner S. Treatment of the common cold in children and adults. Am Fam Physician.2012;86(2):153-9.
- Malesker MA, Challahan-Lyon P, Ireland B, Irwin RS; CHEST Expert Cough Panel. Pharmacologic and nonpharmacologic treatment for acute cough associated with the common cold: CHEST Expert Panel Report. 2017;152(5):1021-37.
- King D, Mitchell B, Williams CP, Spurling GKP. Saline nasal irrigation for acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;(4):CD006821.
- Chang AB, Oppenheimer JJ, Weinberger M, et al; CHEST Expert Cough Panel. 2017;152(3):607-17.
- Alsubaie H, Al-Shamrani A, Alharbi AS, Alhaider S. Clinical practice guidelines: approach to cough in children: the official statement endorsed by the Saudi Pediatric Pulmonology Association (SPPA). Int J Pediatr Adolesc Med. 2015;2:38-43.
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- Barker SJ. Honey for acute cough in children. Paediatr Child Health. 2016;21(4):199-200.
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