INTRODUCTION

Fever is among the most common symptoms assessed and managed by healthcare providers. National Ambulatory Medical Care Survey data shows fever as the leading cause of emergency room visits in children under 15 years,¹ accounting for 16.8% of emergency rooms visits in this age group in 2018, and for 4.5% of emergency room visits overall.² Up to 30% of children visiting their pediatricians have fever as a symptom.³ Fever is more common in children than adults.⁴ While many fevers are nonthreatening and self-limiting, others may point to serious underlying issues, such as infection. Attention to fever has heightened with the emergence of the SARS-COV-2 virus and the subsequent COVID-19 pandemic.

Fever is a common symptom of COVID-19 infection, occurring in 46% of children from birth to age 9 years, 35% in children 10 to 19 years⁵ and in 81.2% of adults.⁶ Airports, businesses, health care organizations, schools and other entities have widely conducted temperature checks as part of COVID-19 infection screening, although a Cochrane rapid review has questioned their utility.⁷ The authors indicated they had low to very low confidence in their findings, however, because most studies failed to clearly describe their screening methods, and the participant types and settings varied greatly.⁷ Consumers may have enhanced awareness of fever presence and its potential to indicate infection because of the pandemic. Increasingly, consumers may turn to pharmacists and pharmacy technicians as accessible and important sources of information on fever measurement and management, including buying temperature monitoring devices.

What is Fever?

Fever is a regulated rise in body temperature higher than the normal core temperature of 100° F (37.8° C).⁸ Core temperature is the temperature of the blood surrounding the hypothalamus, usually defined as 98.6° F. Core temperature is maintained through a feedback system to the hypothalamus’s thermoregulatory center.⁸ Sweating, vasodilation and behavioral mechanisms (e.g., removing clothing, seeking shade, using cool clothes) help return the body to normal core temperature ranges when the feedback system between the thermoregulatory center and thermosensitive neurons in the central nervous system and skin are activated. Body temperature follows a circadian rhythm. Temperature is the lowest in the morning and highest in the late afternoon and may vary up to 1.8° F in adults and 2.58° F in children. The average temperature is most often between 97.5° F (36.4° C) and 98.9° F (37.2° C). In this range, or set point, physiologic and behavioral mechanisms are not activated.⁸

Fever occurs when pyrogenic substances activate the body’s immune defense, which raises the body’s set point. Prostaglandin E₂ (PGE₂) production results from endogenous pyrogens. PGE₂ acts on the thermoregulatory center to raise the body’s temperature set point. This new set point is maintained until pyrogens decrease or the patients takes antipyretic drugs.^8,9 Fever is beneficial in fighting infection by retarding bacterial and viral growth and reproduction.⁹ Fever also enhances production of neutrophils and T-lymphocytes that help the body fight initial infection.⁹

In addition to infection, fever may be caused by pathologic processes, such as malignancy, autoimmune disorders, autoinflammatory disease, or metabolic disorders.⁸ It may also be caused by heatstroke, vigorous activity, or certain drugs. Finally, fever may have unknown origin. Fever may be more pronounced in children and is less pronounced in the elderly.⁸

Distinguishing Fever from Hyperpyrexia and Hyperthermia

Hyperpyrexia is extraordinarily high fever when body temperature exceeds 106.7° F (41.5° C) and results in mental and physical consequences, including dehydration, delirium, seizures, coma, and irreversible neurologic and muscle damage.⁸ Hyperpyrexia may be caused by either a pyrogen or hyperthermia. Hyperthermia is a rise in body temperature that is not accompanied by a rise in the thermoregulatory center’s set point.¹⁰ Heatstroke is an example; the body cannot dissipate heat quickly enough in a warm environment. Exertion can lead to heat stroke, although children and the elderly may suffer from nonexertion heat stroke. Hyperthermia is often characterized by hot, dry skin and CNS dysfunction that leads to delirium, convulsions, or coma.⁹

Drug-induced hyperthermia may be caused by hypersensitivity, altered thermoregulation, a pharmacologic reaction, drug administration, or an idiosyncratic reaction.⁸ Table 1 lists selected drugs that may induce fever. Drug-induced fever may range from 98.9° F (37.2° C) to 109° F (42.8° C) and is not correlated with gender, age, or medical condition. Hypersensitivity to the drug is the most common cause and it usually occurs a week to 10 days after the drug is taken and may be accompanied by rash. When drug-induced hyperthermia is suspected, the offending agent should be discontinued, along with all other medications if feasible. Normal temperature usually returns within 24 to 72 hours. Then medications may be restarted one at a time with monitoring for the fever to recur. The frequency of drug-induced hyperthermia is not well-documented in the outpatient setting, but it may be as high as 10% among hospitalized patients.^11,12

More rarely occurring are malignant hyperthermia and neuroleptic malignant syndrome (NMS). These are potentially life-threatening idiosyncratic reactions. Malignant hyperthermia is a biochemical chain reaction response triggered by commonly used general anesthetics and the paralyzing agent succinylcholine within susceptible individuals' skeletal muscles.¹¹ Malignant hyperthermia-susceptible persons have a genetic mutation that results in the presence of abnormal proteins in the muscle cells of their body. Children and siblings of a person with susceptibility usually have a 50% chance of inheriting a gene defect (RYR-1 and/or CACNA1S) for the condition, and genetic testing can identify the defect.¹¹ Malignant hyperthermia signs include tachycardia, a greatly increased body metabolism, muscle rigidity, and/or body temperature above 104° F (40° C). Severe complications of malignant hyperthermia include cardiac arrest, brain damage, internal bleeding, or failure of other body systems.¹¹

NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs.¹¹ NMS is related to decreased dopamine activity in the brain. NMS typically consists of muscle rigidity, fever, sweating, tachycardia, blood pressure instability, incontinence, and cognitive changes, such as delirium, stupor, or coma.¹¹ It is associated with elevated plasma creatine phosphokinase.¹¹ The incidence of NMS, estimated between 0.2% and 12.2%, is less than in the past because of increased awareness of this syndrome and efforts at prevention. ¹¹ If NMS occurs, the offending drug should be discontinued immediately and supportive care provided.¹¹ Benzodiazepines can be used to treat agitation and restlessness.¹¹

Fever Presentation and Measurement

Fever symptoms may not be specific or occur in all patients. Elevated body temperature is the most important sign of a fever. When assessing patients who present with fever, the first step is to obtain an accurate temperature measurement.⁸  One temperature measurement may not be enough to establish a fever is present so an additional reading should be taken 15 to 30 minutes after the first measurement. After establishing fever presence, asking questions to learn the underlying cause is important. Symptoms that may accompany fever include headache, sweating, malaise, chills, tachycardia, muscle and joint aches and pain, irritability, and loss of appetite.

While subjective measures of fever, such as feeling the forehead for heat, may indicate skin temperature that is higher than normal, they do not objectively reflect the body’s core temperature. Objective measurement of body temperature involves the use of various thermometers at oral, rectal, axillary (underarm), tympanic (ear), or temporal artery sites. When choosing a method to measure temperature, the patient’s age, condition, stress level, and other symptoms should be considered since they may impact temperature measurement results. In addition, the same method and measuring device should be used through the course of an illness. Normal temperature ranges vary at these different sites as well.⁸ Table 2 provides the normal temperature range and fever range for the various body measurement sites. It also shows conditions that may make a site unsuitable for temperature measurement, and outlines advantages and disadvantages associated with each site.^{8,13, 14, 15, 16, 16, 17} The Food and Drug Administration regulates thermometers as medical devices. As such, all approved types of thermometers are accurate and reliable if they are used appropriately.⁸

Patient preference and the criticality of the fever cause may influence the type of device and measurement site used. Regardless of site, it is important that proper procedures be used. New temperature measurement technology has become available, with growth in the noninvasive temperature measurement device market. Pharmacy technicians can be important resources to patients on temperature measurement devices. Recommendations should avoid mercury-based thermometers because of negative environmental impact and the Environmental Protection Agency (EPA) is phasing out their use.⁸

Thermometer Types

There are a number of different thermometer types, and new technologies continue to be introduced. Electronic probe thermometers may be used for rectal, oral, and axillary temperature measurement.⁸ These thermometers contain an electronic transducer, which produces a temperature measurement in 8 to 60 seconds.⁸ Rectal thermometers come in pen or short tip shapes. The short tip design offers greater safety. Oral thermometers may be pen- or, more recently, pacifier-shaped, with rigid or flexible tips. Most thermometers are used with disposable probe covers, require batteries, and have electronic displays. If probe covers are not used, steps to clean and disinfect the thermometer properly should be taken, including wiping the device with an antiseptic, such as alcohol, wiping from the stem toward the tip.⁸

Display types vary, and some are color-coded with red indicating fever. Some may have memory features to track a certain number of temperature measurements, which can be helpful when tracking fever over the course of an illness. Many are water-resistant, and most are bisphenol A (BPA)-free. BPA is a chemical used in the production of numerous plastics. Because it is so widely used, FDA has studied its toxicology and it has concluded because BPA is so rapidly metabolized and eliminated from the body, it is very unlikely to cause negative health effects at real-life exposure levels, yet product manufacturers frequently note if their products are BPA-free.¹⁸

Infrared thermometers are used for ear (tympanic) and temporal forehead measurement. Infrared technology in these thermometers detects heat from the body’s arterial blood supply, producing a temperature measurement in fewer than 5 seconds.⁸ Thermometer placement is very important in producing an accurate reading. Ear thermometers measure temperature across the tympanic membrane, which is close to the hypothalamus.⁸ Many of these thermometers can be set to provide a rectal or oral temperature equivalent since the normal range across measurement sites and devices varies (see Table 2).

Tympanic infrared thermometry, or ITT, has been the subject of numerous studies. One study among critically ill children younger than 7 years of age in pediatric intensive care showed ITT was more accurate at measuring core temperature than rectal, forehead, or axillary measurements during fever cycles in children.¹³ A study of ITT compared to oral and rectal temperature measurement in a pediatric emergency department showed good correlation of ITT with oral and rectal glass thermometry, except in infants younger than 3 months of age.¹⁴ Another comparison of ITT to pulmonary artery thermometry, or PAT, in adult intensive care units and found ITT accurately reflected core temperature compared to the more invasive PAT.¹⁹ A study using a repeated-measures design to describe the accuracy and precision of four noninvasive temperature measurements — oral, ear-based, temporal artery and axillary — compared with pulmonary artery temperature.²⁰ Investigators found that oral (electronic device) and temporal artery (infrared device) temperature measurements agreed closely with the pulmonary artery temperature.²⁰ A more recent study compared infrared temporal and tympanic versus rectal temperature measurement among 995 children 18 years of age or younger.¹⁵ Tympanic measurement was more sensitive and specific than temporal measurement.¹⁵ Tympanic temperature measurement varied from rectal measurement by -0.97° to +1.07° C (-30.3 to +33.9° F). Temporal temperature measurement varied from rectal measurement by -1.2 to +1.5° C (-29.8 to +34.7° F).¹⁵ Tympanic thermometers are significantly better at screening for fever than temporal devices and are especially useful among children aged 6 months to 5 years.¹⁵ Both tympanic and temporal infrared thermometers provide convenience and are noninvasive compared to rectal thermometers.

In older patients, fever may be one manifestation of infection and there are several methods to determine if fever is present among patients in long-term care facilities.²¹ Basal temperatures in older patients may be lower than 98.6° F (37° C). Clinical guidelines note a single temperature reading of ≥100°F (37.8°C) is both a sensitive and specific predictor of infection.²¹ Increased temperature of 2°F (1.1°C) over an oral temperature reading of ≥99°F (37.2°C) or a rectal temperature of ≥99.5°F (37.5°C) on repeated measure is indicative of infection in older patients.²¹ Oral temperature measurement is most common in this population, but rectal temperature measurement may be more accurate than oral and axillary, but it is also more invasive. ITT is considered an alternative temperature measurement in older adults and ITT correlated better to rectal temperature than oral measurement did to rectal temperature in older adults.²¹

These studies indicate that patient factors and criticality may influence the choice of temperature measurement.

Newer technologies include wearable and behind-the-ear thermometers. Wearable thermometers contain a heat-sensitive material that produces a temperature reading in about 2 minutes and also provide continuous readings for up to 48 hours. They are easy to use but are not considered as accurate or reliable as other methods.⁸ Using wearable thermometers on the forehead shows less temperature variation than when they are used on other parts of the body.⁸ The thermometer may detect changes in skin temperature but not core temperature. A behind-the-ear thermometer was introduced in 2012 using a patented noninfrared technology. The skin in the hollow behind the ear is very close to the carotid artery, which carries blood to the brain. To take a reading, the thermometer tip is placed in the hollow behind the ear with results in 1 second. Temperature measurement should be made on the same side of the head because it can vary between the left and right side. A day care study showed 95% of infants slept through the temperature measurement. The behind-the-ear thermometer is noninvasive and convenient.²²

Advantages of the newer technologies include no glass breakages, not necessarily needing disinfection due to probe covers, environmentally friendly with no mercury, less invasive and more convenient. Table 3 outlines instructions for measure temperature by measurement site.

Fever Treatment Goals

Because fever is a physiologic process that is part of an illness rather than the primary illness itself, it is important to determine its underlying cause. Treatment is directed at the underlying cause of the fever.⁹ As noted earlier, hyperthermia needs to be addressed promptly. For nonhyperthermia, the primary goal for treating fever should be to improve the patient’s overall comfort level rather than normalizing the temperature reading.⁹ While fever may be a cause of concern for caregivers, it usually is self-limiting with serious consequences rarely occurring.^8,9 For pediatric patients, clinical treatment guidelines emphasize counseling parents and caregivers on the general well-being of the child, monitoring fever, watching for signs of serious illness, giving adequate fluids, and storing antipyretic medications safely.⁹ Counseling patients, parents and caregivers on fever management is important because studies have shown that nearly three-fourths of caregivers are very concerned about fever, and many parents administer antipyretics for minimal or no fever.^23,24 Studies have found that about half of parents consider a temperature of less than 100.4° F (38° C) to be a fever, and one-quarter of all caregivers would give antipyretics for temperatures of less than 100° F (37.8° C).^25,26 Concerns expressed by caregivers include fever complications of seizures, brain damage, and death.²³

The incidence of febrile seizures is estimated to be 2% to 5% of children between the ages of 6 months and 5 years, with most occurring between 18 and 24 months.⁸ A febrile seizure is one accompanied by fever but without intracranial infection, a metabolic disturbance, or other defined cause.²⁷ Factors that may increase the risk of febrile seizures include a family history of febrile seizures, developmental delay, day care attendance, and neonatal hospital stays.²⁸ Impaired development and epilepsy are unlikely after the occurrence of a single febrile seizure. Recurrence risk increases with family history of epilepsy, in children who experienced the first seizure during their first 12 months, and those who have had multiple seizures already.²⁷ Antipyretics do not reduce the risk of febrile seizure, but they can be used to make the child more comfortable. ²⁸ The pharmacist should ask parents and caregivers about past seizure history in the child and family when assessing fever.

The AAP noted that fever exceeding 101° F (38.3° C) may be treated with both antipyretics and nonpharmacologic therapy (discussed below) to improve patient comfort.⁹ It cautioned that a balance must be achieved between improving comfort and the desire to reduce temperature, especially because there is no evidence proving that reducing fever reduces morbidity and mortality from a febrile illness. Exceptions may be children with chronic conditions or who are critically ill and unable to tolerate the fever’s increase in metabolic demand.⁹

For adult patients, because the average body temperature decreases with age, temperatures that are lower than 101° F (38.3° C) may indicate fever in older patients and may be treated with antipyretics and nonpharmacologic therapy. As noted earlier, a single temperature reading of 100°F (37.8°C) or higher is both a sensitive and specific predictor of infection.²¹ Increased temperature of 2°F (1.1°C) over an oral temperature reading of ≥99°F (37.2°C) or a rectal temperature of ≥99.5°F (37.5°C) on repeated measure is indicative of infection in older patients.²¹

Temperatures exceeding 106°F [41.1°C] measured orally are associated with serious detrimental effects, including but not limited to dehydration, delirium, seizures, coma, irreversible neurologic or muscle damage, especially when caused by hyperthermia rather than fever. The hypothalamus’ homeostatic mechanisms rarely allow a core temperature to exceed 106.0°F from fever. But fevers less than 106.0°F can be serious and life-threatening in patients who have heart disease or pulmonary dysfunction. Older patients are at a higher risk for fever-related complications because of their decreased thirst perception and ability to perspire.⁸

Nonpharmacologic Therapy

Adequate fluid intake to prevent dehydration is the primary nonpharmacologic therapy for fever.⁸ Adults should increase fluid intake by 60 mL to 120 mL (3 ounces to 4 ounces) per hour. Children should increase fluid intake by 30 mL to 60 mL (1 ounces to 2 ounces) per hour. Fluids may include fruit juice, water, sport drinks, electrolyte replacement products, and popsicles. Patients with diarrhea should avoid fruit juice and sport drinks because the sugar content may worsen the condition.⁸ Bathing and sponge baths using lukewarm or moderately warm water may facilitate the dissipation of heat, but they are of limited use and may increase shivering and ultimately fever. They also may be uncomfortable for patients. If they are used, alcohol should not be used as it can result in alcohol poisoning, with infants and children at greater risk for poisoning than adults.⁸ Patients can be advised to wear light clothing and maintain comfortable room temperature, also seek shade if outdoors.

Pharmacologic Therapy

Pharmacologic therapy for fever consists of antipyretics, including acetaminophen, aspirin, ibuprofen, and naproxen sodium. Antipyretics work by decreasing PGE₂ synthesis through inhibition of the cyclooxygenase enzyme in the brain.⁸ This decreases the feedback between the hypothalamus and the thermoregulatory center neurons. Acetaminophen works only within the CNS, while the other agents also work peripherally. Acetaminophen, ibuprofen and naproxen have an onset of action of less than an hour, with peak temperature reduction at 2 hours.⁸ Acetaminophen’s duration of effect is 4 to 6 hours, while ibuprofen’s is 6 to 8 hours. Table 4 lists recommended dosages of antipyretics for adult patients.²⁹ Table 5 lists recommended dosing of acetaminophen and ibuprofen for pediatric patients.^30,31

Studies that have compared the effectiveness of acetaminophen and ibuprofen have found in variable results.⁸ The AAP noted there is consensus that both drugs are more effective than placebo and that ibuprofen is possibly more effective than acetaminophen when given as a single or repeated dose.⁸

Combination therapy alternating acetaminophen and ibuprofen also has been studied. While studies have provided limited evidence that combination therapy may be more effective at lowering temperature, safety issues and lack of effectiveness in improving discomfort — the primary treatment goal in fever — remain questions for this practice.⁸ Combination therapy also may prove more difficult to dose, contributing to medication errors. Because of dosing issues and potential medication errors, the AAP does not recommend alternating acetaminophen and ibuprofen.⁹

Precautions

Acetaminophen is generally very well tolerated when used as directed. However, liver toxicity with acetaminophen may occur and is a serious, dose-dependent effect. The maximum recommended dosage is 75 mg/kg/day (adults not to exceed 4000mg/day).²⁹ Signs associated with acetaminophen toxicity include nausea, vomiting, diarrhea, and excessive sweating. Care should be taken not to exceed this threshold by administering higher doses more frequently than recommended. Because acetaminophen is metabolized by the liver, dosage adjustments may need to be made in patients with heavy alcohol use, advanced age, liver disease, and concurrent use of drugs that slow acetaminophen metabolism with some experts recommending a maximum daily dose of 2000mg/day.²⁹ Patients should also be alerted to the fact that many combination products contain acetaminophen and should not be used in combination. The pharmacy technician should help point out product ingredients and potential duplication when helping patients locate products in the pharmacy. Allergic reactions can occur and the pharmacist should counsel the patient to discontinue the medication if they experience skin reddening, blisters or rash.²⁹

The most common side effects with ibuprofen and naproxen are gastrointestinal (GI) in nature, and include heartburn, nausea, anorexia, and dyspepsia. Pharmacists should counsel patients to take non-steroidal anti-inflammatory drugs (NSAIDs) with food, milk, or antacids to minimize potential GI side effects and to take with a full glass of liquid.²⁹ Patients who ingest 3 or more alcoholic drinks per day or who are on anticoagulant therapy should be cautioned about the increased risk of adverse GI events, including stomach bleeding. There is increased bleeding risk in general with NSAIDs and that is a consideration in recommending their use.³² NSAIDs may also decrease renal blood flow and glomerular filtration rate. Advanced age, hypertension, diabetes, atherosclerotic cardiovascular disease, and use of diuretics appear to increase the risk of renal toxicity with ibuprofen use.²⁹ Patients with a history of impaired renal function, congestive heart failure, or diseases that compromise renal hemodynamics should not self-treat with NSAIDs. Because of case reports of kidney toxicity in febrile children, ibuprofen should be used with caution in children who are dehydrated or have complicated illnesses, such as cardiovascular disease or pre-existing renal disease, or are using other nephrotoxic agents.⁸

 In 2015, FDA strengthened warnings regarding the risk of heart attack and stroke for prescription and over-the-counter NSAIDs, including ibuprofen and naproxen.³³ The pharmacist should counsel patients to watch for symptoms that may suggest heart attack and stroke, including chest pain, trouble breathing, weakness in one part or side of the body, or slurred speech. Ibuprofen is not indicated for use in children younger than 6 months of age.

The salicylates cause dyspepsia and GI irritation more frequently than the OTC NSAIDs. Taking aspirin with food may help to improve tolerability. There are numerous formulations available to reduce GI impact: buffered products in tablet or effervescent forms, enteric-coated products and sustained-release products.²⁹ Aspirin should be used with caution in patients with a history of peptic ulcer disease or those taking anticoagulant or other antiplatelet medications and should be avoided in patients with coagulation disorders. All salicylates should be avoided in patients with a history of gout or hyperuricemia because of dose-related effects on renal uric acid handling. Aspirin is not recommended in children younger than 15 years of age due to the increased risk of Reye’s syndrome.³⁴

The pharmacist should educate and counsel patients, parents and caregivers about the appropriate use, dosing, and administration of antipyretic drugs. Increasing medication errors and adverse events in the last few years have included duplicate ingredients by using multiple products with the same ingredient, and incorrect dosing for children.³⁵ One study found up to half of all parents administer incorrect doses of antipyretics.³⁶ Another study showed only 30% of parents were able to accurately measure the correct acetaminophen dose.³⁷ Researchers also found 62% of pediatric patients received an incorrect dose of acetaminophen, while 26% received an incorrect dose of ibuprofen.³⁷ Parents who understood that acetaminophen and ibuprofen should be dosed by their child’s weight were less likely to give inaccurate doses.³⁶

In May 2011, FDA released guidelines to address inaccurate dosing issues of liquid OTC products that contain any dispensing device.³⁵ The guidance requires including a dosing device calibrated to the product’s dosage directions for all oral liquid OTC products that is to be used only with the product it is packaged; it must have visible markings even when liquid is in the device. The pharmacist should counsel parents and caregivers about dosing by weight and emphasize using the dosing device that comes with the prescribed product. The pharmacy technician can point out the weight-based dosing on the product label and show the patient the dosing device.

Conclusion

Helping patients, parents and caregivers understand fever and its potential benefits and risks is an important starting point for pharmacists when assessing patients and providing recommendations for managing and treating fever. Pharmacists and pharmacy technicians are important sources of information on temperature measurement devices and how to use them, including the advantages and disadvantages of each type of device. When fever is present, patients should monitor their general well-being, fever, and watch for signs of serious illness and maintain adequate fluid intake. Antipyretic medications can lower fever and the pharmacist should describe the appropriate use, dosing, and administration of antipyretic drugs to patient. The pharmacy technician should be familiar with which products the pharmacy stocks and where they are located, including thermometers, and be able to point to discuss their differences and use with patients. The pharmacy technician should also be able to help patients read product labeling and help avoid product selection with duplicate active ingredients. Customer questions should be triaged to the pharmacist as appropriate. Given the frequency of fever symptoms and the COVID-19 pandemic, the pharmacy team can serve as an important resource to patients, parents and caregivers on appropriate fever assessment and management.

PRACTICE POINTS

• Fever is a regulated rise in body temperature higher than the normal core temperature of 100®F (37.8°C). Older adults frequently have lower basal temperatures than this.
• Fever is confirmed by using an appropriate, FDA-regulated thermometer.
• When choosing a method to measure temperature, the patient’s age, condition, stress level, and other symptoms should be considered as they may impact temperature measurement results.
• It is important to determine the underlying cause of fever. Fever is usually self-limiting unless the temperature is ≥106.0°F (41.1°C).
• The American Academy of Pediatrics notes fever that exceeds 101°F (38.3°C) may be treated with both antipyretics and non-pharmacologic therapy to improve patient comfort.
• Acetaminophen and ibuprofen are OTC antipyretic medications for use in adults and children. Help patients choose products that do not have duplicate ingredients and instruct them on proper dosing using included dosing devices.
• For fevers not responding to self-treatment after 3 days in those over 2 years of age and after 24 hours for those children under 2 years of age, referral for further evaluation is appropriate or if fever is greater than 104.0°F (38.0°C).

REFERENCES

1. Niska R, Bhuiya F, Xu J. National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010;(26):1-31.
2. Cairns C, Kang K, Santo L. National Hospital Ambulatory Medical Care Survey: 2018 emergency department summary tables. Accessed May 28, 2021. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2018-ed-web-tables-508.pdf.
3. Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: have parental misconceptions about fever changed in 20 years. Pediatrics. 2001;107(6):1241–1246.
4. Fever in children: an overview. National Center for Biotechnology Information, U.S. National Library of Medicine. Updated June 6, 2019. Accessed June 18, 2021. https://www.ncbi.nlm.nih.gov/books/NBK279455/
5. Deville JG, Son E, Ouellette C. COVID-19: Clinical manifestations and diagnosis in children. May 10, 2021. UpToDate.com website. Accessed May 28, 2021. https://www.uptodate.com/contents/covid-19-clinical-manifestations-and-diagnosis-in-children#H3964662040.
6. Bennett S, Tafuro J, Mayer J, et.al. Clinical features and outcomes of adults with coronavirus disease 2019: A systematic review and pooled analysis of the literature. Int J Clin Pract. 2021;75(3):e13725. Accessed May 24, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536970/pdf/IJCP-9999-e13725.pdf.
7. Viswanathan M. Cochrane Rapid Review investigates the effectiveness of screening for COVID-19. October 16, 2020. Accessed May 28, 2021. https://www.cochrane.org/news/cochrane-rapid-review-investigates-effectiveness-screening-covid-19.
8. Lemay V, Feret B. Chapter 6: Fever. “Handbook of Nonprescription Drugs.” 20th ed. American Pharmaceutical Association; 2020:113-128. https://doi.org/10.21019/9781582123172.ch6
9. Sullivan JE, Farrar HC and the Section on Clinical Pharmacology and Therapeutics, and Committee on Drugs. Clinical report- fever and antipyretic use in children. Pediatrics.127:580-587. . Accessed May 28 2021.http://pediatrics.aappublications.org/content/early/2011/02/28/peds.2010-3852.full.pdf+html
10. Halloran LL, Bernard DW. Management of drug-induced hyperthermia. Curr Opin Pediatr. 2004;16:211-215.
11. Musselman ME, Saely S. Diagnosis and treatment of drug-induced hyperthermia. Am J Health-Syst Pharm.2013;70(1):34–42. doi: 10.2146/ajhp110543
12. Cuddy, ML. The effects of drugs on thermoregulation. ACCN Clin Issues.2004;15(2):238–253. 
13. El-Radhi AS, Barry W. Thermometry in paediatric practice. Arch Dis Child. 2006;91:351-356.
14. Nimah MM, Bshesh K, Callahan JD, Jacobs RB. Infrared tympanic thermometry in comparison with other temperature measurement techniques in febrile children. Pediatr Crit Care Med. 2006;7:48-55.
15. Mogensen CB, Wittenhoff L, Fruerhøj G, Hansen S. Forehead or ear temperature measurement cannot replace rectal measurements, except for screening purposes. BMC Pediatr. 2018;18(1):15.
16. Dybwik K, Nielsen EW. Infrared temporal thermometry. Tidsskr Nor Laegeforen. 2003;123(21):3025-3026.
17. Erickson RS, Kirklin SK. Comparison of ear-based, bladder, oral, and axillary methods for core temperature measurement. Crit Care Med. 1993;21(10):1528-1534.
18. What does U.S. government research tell us about BPA? Facts About BPA. American Chemical Council. Accessed June 19, 2021. https://www.factsaboutbpa.org/bpa-overview/bpa-basics?gclid=CjwKCAjwq7aGBhADEiwA6uGZp6c3DnTwffx5SBzzPaEcu5WKKmpglcbQf4kG8v_f3bLEi8yrVKlxCRoCXc4QAvD_BwE.
19. Bock, M., Hohlfeld, U., Engeln, K.v. et al.The accuracy of a new infrared ear thermometer in patients undergoing cardiac surgery. Can J Anesth. 2005;52:1083. https://doi.org/10.1007/BF03021609
20. Lawson L, Bridges EJ, Ballou I, et. al. Accuracy and precision of noninvasive temperature measurement in adult intensive care patients. Am J Crit Care. 2007;16[(5)485-496.]
21. High KP, Bradley SF, Gravenstein S, et al. Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America. J Am Geriatr Soc. 2009;57(3):375-394. doi:10.1111/j.1532-5415.2009.02175.x
22. Behind the ear -- a new site to measure for fever [press release]. Southborough, MA: Kaz, Inc. December 15, 2011. Accessed May 28, 2021. https://www.prnewswire.com/news-releases/behind-the-ear----a-new-site-to-measure-for-fever-135650533.html.
23. Poirier MP, Collins EP, McGuire E. Fever phobia: a survey of caregivers of children seen in a pediatric emergency department. Clin Pediatr. 2010;49:530-534.
24. Bilenko N, Tessler H, Okbe R, Press J, Gorodischer R. Determinants of antipyretic misuse in children up to 5 years of age: a crosssectional study. Clin Ther. 2006;28(5):783–793.
25. Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: have parental misconceptions about fever changed in 20 years. Pediatrics. 2001;107(6):1241–1246.
26. Kramer MS, Naimark L, Leduc DG. Parental fever phobia and its correlates. Pediatrics. 1985;75(6):1110–111 .
27. Steering committee on quality improvement and management, subcommittee on febrile seizures. Febrile seizures: clinical practice guidelines for the long-term management of the child with simple febrile seizures. Pediatrics. 2008:121:1281-1286.
28. Millar JS. Evaluation and treatment of the child with febrile seizure. Am Fam Physician. 2006;73:1761-1764.
29. Lexicomp.® Version 6.4.5. 2021 UptoDate Inc. Wolters Kluwer. Accessed June 20, 2021.
30. Dlugosz CK, Chater RW, Engle JP. Appropriate use of nonprescription analgesics in pediatric patients. J Pediatr Health Care.2006;20(5):316-325.
31. Kaiser Permanente. Recommended pediatric dosing: acetaminophen/ibuprofen. November 2020. Accessed May 28, 2021. https://mydoctor.kaiserpermanente.org/ncal/Images/Ibuprofen%20and%20Acetaminophen%20(Tylenol)%20Recommended%20Pedi%20Dosing%20(00065-000)_tcm75-14511.pdf.
32. U.S. Food and Drug Administration. Over-the-counter drug products containing internal analgesic/antipyretic active ingredients; required warnings and other labeling. CFR: Code of Federal Regulations. Title 21, Part 201, Section 201.326. Updated June 23, 2016. Accessed June 20, 2021. http://www.ecfr.gov/cgi-bin/text-idx?SID=d896e8f8b1ddcea5d08baa1c5086c5f5&mc=true&node=se21.4.201_1326&rgn=div8.
33. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. July 9, 2015. Accessed June 20, 2021. http://www.fda.gov/Drug’s/DrugSafety/ucm451800.htm
34. What is the role of aspirin in triggering Reye’s Syndrome? The National Reye’s Syndrome Foundation Web site. Accessed June 20, 2021. http://www.reyessyndrome.org/.
35. Food and Drug Administration. Guidance for Industry: Dosage Delivery Devices for Orally Ingested OVER-THE-COUNTER Liquid Drug Products. Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; May 2011. Accessed May 28, 2021. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM188992.pdf,
36. Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatr Emerg Care. 2000;16(6):394–397.
37. Wright AD, Liebelt EL. Alternating antipyretics for fever reduction in children: an unfounded practice passed down to parents from pediatricians. Clin Pediatr. 2007;46:146-150.

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