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Antiviral Therapy and Prophylaxis for Influenza in Children Committee on Infectious Diseases Pediatrics 2007;119;852 DOI: 10.1542/Peds.2007-0224

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Antiviral Therapy and Prophylaxis for Influenza in Children Committee on Infectious Diseases Pediatrics 2007;119;852 DOI: 10.1542/Peds.2007-0224 CLINICAL REPORT Guidance for the Clinician in Rendering Antiviral Therapy and Prophylaxis Pediatric Care for Influenza in Children Committee on Infectious Diseases ABSTRACT Antiviral agents are available that are safe and effective for the treatment and prophylaxis of influenza virus infections in children. The neuraminidase inhibitors (oseltamivir [Tamiflu] and zanamivir [Relenza]) are preferred agents because of current widespread resistance to the adamantanes (amantadine [Symmetrel] and rimantadine [Flumadine]). Therapy should be provided to children with influenza infection who are at high risk of severe infection and to children with moderate- to-severe influenza infection who may benefit from a decrease in the duration of symptoms. Prophylaxis should be provided (1) to high-risk children who have not yet received immunization and during the 2 weeks after immunization, (2) to unimmunized family members and health care professionals with close contact with high-risk unimmunized children or infants who are younger than 6 months, and (3) for control of influenza outbreaks in unimmunized staff and children in an institutional setting. Testing of current H5N1 avian influenza virus isolates, the potential agents of pandemic influenza, suggests susceptibility to oseltamivir and zanamivir. Because no prospective data exist on the efficacy of these agents in humans for H5N1 strains, the dosage and duration of therapy in adults and children may differ from those documented to be effective for epidemic influenza strains. www.pediatrics.org/cgi/doi/10.1542/ peds.2007-0224 INTRODUCTION doi:10.1542/peds.2007-0224 Antiviral agents for treatment and prophylaxis of influenza are safe and effective All clinical reports from the American in children. Annual immunization against influenza is the preferred strategy for Academy of Pediatrics automatically prevention of infection, but certain situations exist in which the use of antiviral expire 5 years after publication unless agents is beneficial. reaffirmed, revised, or retired at or before that time. The morbidity and mortality of epidemic influenza in unimmunized children is The guidance in this report does not 1–5 substantial, particularly in those younger than 2 years. The purpose of this report indicate an exclusive course of treatment is to offer guidance regarding antiviral treatment and prophylaxis to clinicians or serve as a standard of medical care. Variations, taking into account individual caring for children during yearly influenza epidemics and to provide resources for circumstances, may be appropriate. information on antiviral treatment in the event of an influenza pandemic, because Key Words no prospective human data currently exist on which to base recommendations for influenza, children, influenza antiviral, treatment of infections caused by potential H5N1 pandemic influenza virus strains. oseltamivir, zanamivir, amantadine, rimantadine, ribavirin Abbreviations ANTIVIRAL DRUGS FOR EPIDEMIC AND PANDEMIC INFLUENZA NAI—neuraminidase inhibitor Two classes of antiviral medications are currently available for treatment or FDA—Food and Drug Administration prophylaxis of influenza infections: neuraminidase inhibitors (NAIs) (oseltamivir CNS—central nervous system PEDIATRICS (ISSN Numbers: Print, 0031-4005; [Tamiflu; Roche Laboratories, Nutley, NJ] and zanamivir [Relenza; GlaxoSmith- Online, 1098-4275). Copyright © 2007 by the Kline, Research Triangle Park, NC]) and the adamantanes (amantadine [Symme- American Academy of Pediatrics 852 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 28, 2021 TABLE 1 Dosing Recommendations for Antiviral Agents for Treatment and Prophylaxis of Influenza Drug Formulations Dosing Recommendations Treatment Prophylaxis Children Adults Children Adults Downloaded from Oseltamivir 75-mg capsule; For treatment, children Ն12 mo should receive ϳ4 mg/kg per d divided into 2 150 mg/d divided Յ15 kg Ͼ15–23 kg Ͼ23–40 kg Ͼ40 kg 75 mg once daily (Tamiflu) 60 mg/5 mL doses for a 5-d treatment course into 2 doses for suspension Յ15 kg Ͼ15–23 kg Ͼ23–40 kg Ͼ40 kg 5 d 30 mg once 45 mg once 60 mg once 75 mg once 60 mg/d divided 90 mg/d divided 120 mg/d divided 150 mg/d divided daily daily daily daily into 2 doses into 2 doses into 2 doses into 2 doses www.aappublications.org/news Children Ն7 y and Adults Children Ն5 y and Adults Zanamivir 5mgper 2 inhalations (10 mg total per dose), twice daily for 5 d 2 inhalations (10 mg total per dose), once daily for 10 d (Relenza) inhalation (Diskhaler) 1–9 y 9–12 y Adults 1–9 y 9–12 y Adults Amantadine 100-mg tablet; 5–8 mg/kg per d as a single daily 200 mg/d divided into 2 doses (not 200 mg/d, either Same as treatment dosea,b Same as treatment dosea,b Same as treatment (Symmetrel) 50 mg/5 mL dose or divided into 2 doses but studied as a single daily dose)a,b; treat as a single daily dosea,b suspension not to exceed 150 mg/da,b; treat for 24–48 h after the disappearance dose or divided byguestonSeptember 28,2021 for 24–48 h after the of signs and symptoms into 2 dosesa,b; disappearance of signs and treat for 24–48 symptoms h after the disappearance of signs and symptoms PEDIATRICS Volume 119, Number 4, April 2007 1–9 y Ն10 y Adults 1–9 y Ն10 y Adults Rimantadine 100-mg tablet; Not FDA approved for treatment in children, but published data exist on safety 200 mg/d, either 5 mg/kg per d once daily, 200 mg/d, either as a single 200 mg/d, either (Flumadine) 50 mg/5 mL and efficacy45 as a single daily not to exceed 150 mga,b daily dose or divided into as a single daily suspension 6.6 mg/kg per d (maximum 150 mg/ 200 mg/d, either as a single daily dose dose or divided 2 dosesa,b dose or divided kg per d) divided into 2 doses or divided into 2 dosesa into 2 dosesa into 2 dosesa,b a Amantadine and rimantadine should only be used for prophylaxis in winter seasons during which a majority of influenza A virus strains isolated are adamantane-susceptible; the adamantanes should not be used for primary therapy because of the rapid emergence of resistance. However, for those requiring adamantane therapy, a treatment course of approximately 7 days is suggested, or 24 to 48 hours after the disappearance of signs and symptoms. b For prophylaxis, antiviral drugs should be continued for the duration of known influenza A in the community because of the potential for repeated and unknown exposures or until immunity can be achieved after immunization. 853 trel; Endo Pharmaceuticals, Chads Ford, PA] and riman- the host cell membrane attachment site, thus freeing the tadine [Flumadine; Forest Pharmaceuticals, St Louis, virus to infect other cells. The NAI antiviral agents in- MO]). Guidelines for the use of these 4 antiviral agents hibit productive infection by preventing release of infec- are summarized in Table 1. Little is currently known tious virus from host cell membranes and promote about the efficacy of antiviral agents against H5N1 clumping of viral particles via binding to glycoproteins strains of influenza A virus that may ultimately cause an that are present in respiratory mucus.10,12 influenza pandemic. Current concerns about widespread resistance to the adamantanes limit the usefulness of this Oseltamivir Treatment class of agents for both epidemic strains and H5N1 Oseltamivir has been investigated in a prospective, ran- strains of influenza A virus. domized, blinded, placebo-controlled study in children 1 The NAIs block the action of influenza neuramini- to 12 years of age.14 A 5-day treatment course was asso- dase, an enzyme present on the viral envelope that ciated with a median reduction in overall clinical illness provides for the efficient release of progeny virion par- of 36 hours and a reduction in fever of 25 hours in ticles from the surface of an infected cell. The target of oseltamivir-treated children compared with placebo re- the adamantanes is the viral M2 matrix protein, an cipients. Furthermore, the incidence of acute otitis me- ion-channel protein that spans the viral envelope’s lipid dia (assessed by tympanometry and physician-prescribed bilayer and is required for viral uncoating. Detailed re- antimicrobial therapy) was reduced by 44% compared views of antiviral therapy have been published recent- with placebo recipients. A significant decrease in viral ly.6–12 shedding was also noted in treated children, with few With all antiviral medications, treatment earlier in the children still shedding virus on day 4 of therapy. The course of infection is likely to offer maximum benefit. most common adverse drug effects noted were gastroin- Treatment starting as early as 12 hours after onset of testinal tract disturbances, with vomiting in 14% of os- symptoms has the greatest impact on disease resolu- eltamivir-treated children compared with 8% of chil- tion.13 Most studies have been performed in otherwise dren who were given placebo. healthy children who had symptoms for less than 48 In studies of unimmunized children with asthma 6 to hours, with the reported improvement in outcomes be- 12 years of age who received oseltamivir or placebo, no ing most profound in those children who were provided difference in the median time to freedom from illness early therapy. Although study populations may not ac- was demonstrated, but a significant improvement in pul- curately reflect the diverse patient population seen by monary function was noted on day 6 after treatment.15 health care professionals, the longer symptoms extend For oseltamivir-treated children whose therapy was beyond 48 hours before starting treatment, the less likely started within 24 hours of onset, a more dramatic dif- the child will benefit from antiviral therapy. ference in alleviation of all symptoms was noted, com- The antiviral agents discussed below that are ap- pared with those who were started on therapy after 24 to proved for treatment and/or prophylaxis of influenza are 48 hours of symptoms.
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