title: Antivirals for influenza: strategies for use in pediatrics.
abstract: Influenza infection is annually responsible for significant morbidity and mortality, particularly among the very young and old. Recently updated guidelines recommend influenza vaccination of all children aged 6 months to 18 years; however, childhood vaccination remains underutilized. Furthermore, concerns over the reduced efficacy of vaccination in children have further heightened the need for effective treatment schemes. Antiviral therapies have emerged as attractive options in the battle against influenza infection. These agents include the adamantanes (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir, oseltamivir, and peramivir). Broad-scale use of adamantane antivirals has been severely limited in recent years because of high resistance rates and their inability to cover influenza type B. Neuraminidase inhibitors cover influenza types A and B, and have been promulgated to first-line therapy because of historically low resistance rates and relatively infrequent side effects. Moreover, these agents are effective options in combating non-seasonal influenza strains, including H5N1 and pandemic 2009 H1N1. Oseltamivir may be particularly appealing for treating children since it is available in multiple oral dosage formulations, whereas commercially available zanamivir use is limited in young children because it requires inhalation. However, the emergence of resistance to oseltamivir among influenza A strains may limit its usefulness. Additional concerns with neuraminidase inhibitor use in pediatrics center around emerging reports, primarily from Japan, that have temporally linked oseltamivir to significant neuropsychiatric events in children of varying ages. Numerous novel antiviral agents are under development, but most are far from market approval. In addition to treating and preventing the initial burden of pediatric influenza infection, antiviral therapies may significantly reduce secondary bacterial infections (including pneumonia and otitis media), unnecessary antibiotic prescribing, and healthcare-associated costs.
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA. ssmithm@ufl.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Smith
authors.forename: John G
authors.initials: JG
authors.lastname: Gums
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009975:Orthomyxoviridae / Q000187:drug effects / Q000201:enzymology; D010372:Pediatrics / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D009439:Neuraminidase; D000218:Adamantane
references.citation: MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60
references.pmid: 18685555
references.citation: Pediatr Int. 2002 Feb;44(1):43-6
references.pmid: 11982870
references.citation: J Infect Dis. 2006 Nov 1;194 Suppl 2:S133-8
references.pmid: 17163386
references.citation: J Infect Dis. 2004 Oct 15;190(8):1369-73
references.pmid: 15378427
references.citation: N Engl J Med. 2000 Nov 2;343(18):1282-9
references.pmid: 11058672
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8682-6
references.pmid: 15173583
references.citation: Antimicrob Agents Chemother. 2003 Aug;47(8):2518-25
references.pmid: 12878514
references.citation: Semin Respir Infect. 1992 Mar;7(1):26-37
references.pmid: 1609165
references.citation: JAMA. 2006 Feb 22;295(8):891-4
references.pmid: 16456087
references.citation: MMWR Recomm Rep. 2007 Jul 13;56(RR-6):1-54
references.pmid: 17625497
references.citation: Antiviral Res. 2000 Jul;47(1):1-17
references.pmid: 10930642
references.citation: N Engl J Med. 2005 Sep 29;353(13):1363-73
references.pmid: 16192481
references.citation: Antimicrob Agents Chemother. 2004 Dec;48(12):4855-63
references.pmid: 15561867
references.citation: CMAJ. 2003 Jan 7;168(1):49-56
references.pmid: 12515786
references.citation: MMWR Morb Mortal Wkly Rep. 2007 Sep 21;56(37):963-5
references.pmid: 17882126
references.citation: Antimicrob Agents Chemother. 2006 Apr;50(4):1470-9
references.pmid: 16569867
references.citation: Antiviral Res. 2007 Nov;76(2):186-93
references.pmid: 17719657
references.citation: MedGenMed. 2007 Oct 30;9(4):23
references.pmid: 18311373
references.citation: Pediatr Infect Dis J. 2001 Feb;20(2):127-33
references.pmid: 11224828
references.citation: Antiviral Res. 2008 Dec;80(3):266-71
references.pmid: 18601954
references.citation: Lancet. 1998 Dec 12;352(9144):1877-81
references.pmid: 9863784
references.citation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD002745
references.pmid: 18254006
references.citation: Lancet. 2006 Jan 28;367(9507):303-13
references.pmid: 16443037
references.citation: Pediatrics. 2008 Apr;121(4):e1016-31
references.pmid: 18381500
references.citation: Toxicol Appl Pharmacol. 1969 Nov;15(3):642-65
references.pmid: 4982107
references.citation: N Engl J Med. 2000 Dec 14;343(24):1778-87
references.pmid: 11114318
references.citation: J Med Virol. 1987 Mar;21(3):249-55
references.pmid: 3549971
references.citation: Can J Infect Dis. 2000 Nov;11(6):295-8
references.pmid: 18159303
references.citation: J Pediatr. 2006 Dec;149(6):755-762
references.pmid: 17137887
references.citation: Pediatr Int. 2005 Aug;47(4):484
references.pmid: 16091087
references.citation: Tohoku J Exp Med. 2008 Feb;214(2):129-38
references.pmid: 18285670
references.citation: Clin Infect Dis. 2010 Jun 1;50(11):1493-6
references.pmid: 20415572
references.citation: Clin Infect Dis. 2008 Aug 1;47(3):339-45
references.pmid: 18582202
references.citation: N Engl J Med. 2005 Dec 15;353(24):2559-67
references.pmid: 16354892
references.citation: Jpn J Tuberc Chest Dis. 1971 Jul;17(1):1-7
references.pmid: 4948478
references.citation: N Engl J Med. 2000 Mar 2;342(9):661-2
references.pmid: 10702061
references.citation: Antimicrob Agents Chemother. 1999 Jul;43(7):1616-20
references.pmid: 10390212
references.citation: Antimicrob Agents Chemother. 2007 Mar;51(3):845-51
references.pmid: 17194832
references.citation: Pediatr Infect Dis J. 2008 Aug;27(8):738-43
references.pmid: 18664986
references.citation: MMWR Morb Mortal Wkly Rep. 2008 Apr 18;57(15):404-9
references.pmid: 18418347
references.citation: Pediatr Int. 2003 Jun;45(3):366-7
references.pmid: 12828601
references.citation: MMWR Recomm Rep. 2004 May 28;53(RR-6):1-40
references.pmid: 15163927
references.citation: Pediatr Infect Dis J. 2010 Mar;29(3):195-8
references.pmid: 19949363
references.citation: Antiviral Res. 2006 Jan;69(1):39-45
references.pmid: 16325932
references.citation: Eur J Clin Microbiol Infect Dis. 2000 Nov;19(11):834-42
references.pmid: 11152308
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8676-81
references.pmid: 15173599
references.citation: Antivir Ther. 2003 Jun;8(3):183-90
references.pmid: 12924534
references.citation: J Antimicrob Chemother. 2003 Jan;51(1):123-9
references.pmid: 12493796
references.citation: Pediatrics. 1987 Aug;80(2):275-82
references.pmid: 3302925
references.citation: Jpn J Tuberc Chest Dis. 1968 Dec;15(1):17-26
references.pmid: 4906644
references.citation: Lancet. 2009 Oct 17;374(9698):1312-3
references.pmid: 19837238
references.citation: Expert Opin Pharmacother. 2008 Feb;9(2):151-61
references.pmid: 18201141
references.citation: Lancet. 2005 Oct 1;366(9492):1175-81
references.pmid: 16198766
references.citation: JAMA. 2007 Apr 4;297(13):1435-42
references.pmid: 17405969
references.citation: BMJ. 2007 Jun 16;334(7606):1232-3
references.pmid: 17569896
references.citation: J Infect. 2000 Jul;41(1):73-83
references.pmid: 10942644
references.citation: Drug Saf. 1999 Oct;21(4):267-81
references.pmid: 10514019
references.citation: Lancet. 1971 Jul 17;2(7716):113-5
references.pmid: 4104457
references.citation: Antimicrob Agents Chemother. 2008 Sep;52(9):3284-92
references.pmid: 18625765
references.citation: BMJ. 2009 Aug 10;339:b3172
references.pmid: 19666987
references.citation: Antimicrob Agents Chemother. 2004 Dec;48(12):4542-9
references.pmid: 15561823
references.citation: Antiviral Res. 2005 Oct;68(1):10-7
references.pmid: 16087250
references.citation: N Engl J Med. 2010 Jan 7;362(1):88-9
references.pmid: 20032317
references.citation: Pediatr Infect Dis J. 2000 May;19(5):410-7
references.pmid: 10819336
references.citation: Antiviral Res. 2008 Apr;78(1):91-102
references.pmid: 18328578
references.citation: Clin Infect Dis. 2007 Dec 15;45(12):1568-75
references.pmid: 18190317
references.citation: Pharmacoeconomics. 1996;9 Suppl 3:26-33; discussion 50-3
references.pmid: 10160483
references.citation: Emerg Infect Dis. 2009 Apr;15(4):552-60
references.pmid: 19331731
references.citation: J Infect Dis. 2004 Feb 1;189(3):440-9
references.pmid: 14745701
references.citation: N Engl J Med. 2007 Feb 15;356(7):685-96
references.pmid: 17301299
references.citation: Cell. 1992 May 1;69(3):517-28
references.pmid: 1374685
references.citation: J Am Chem Soc. 1997 Jan 29;119(4):681-90
references.pmid: 16526129
references.citation: J Virol. 1994 Mar;68(3):1551-63
references.pmid: 7508997
references.citation: Clin Infect Dis. 2009 Jan 1;48 Suppl 1:S3-13
references.pmid: 19067613
references.citation: Pediatrics. 2007 Mar;119(3):e587-95
references.pmid: 17332179
references.citation: Clin Infect Dis. 2008 Sep 15;47(6):735-43
references.pmid: 18694344
references.citation: Nature. 1983 May 5-11;303(5912):35-40
references.pmid: 6843658
references.citation: Pediatr Infect Dis J. 2005 Jun;24(6):575-6
references.pmid: 15933579
references.citation: Respir Res. 2006 Mar 23;7:43
references.pmid: 16553963
references.citation: Epidemiology. 2009 Jul;20(4):619-21
references.pmid: 19367165
references.citation: Ann Pharmacother. 2010 Jul-Aug;44(7-8):1240-9
references.pmid: 20516360
references.citation: Paediatr Drugs. 2001;3(3):229-36
references.pmid: 11310719
references.citation: JAMA. 2009 Mar 11;301(10):1042-6
references.pmid: 19255111
references.citation: JAMA. 2000 Feb 23;283(8):1016-24
references.pmid: 10697061
references.citation: Drug Saf. 1998 Sep;19(3):233-41
references.pmid: 9747669
references.citation: BMJ. 2007 Jul 14;335(7610):59
references.pmid: 17626921
references.citation: Infect Dis Clin North Am. 1987 Jun;1(2):441-57
references.pmid: 3332797
references.citation: Clin Infect Dis. 1998 Jun;26(6):1418-24
references.pmid: 9636873
references.citation: JAMA. 2004 Sep 15;292(11):1333-40
references.pmid: 15367555
references.citation: Annu Rev Med. 2008;59:397-413
references.pmid: 17939760
references.citation: Virology. 1991 Feb;180(2):617-24
references.pmid: 1989386
references.citation: Nat Rev Drug Discov. 2007 Dec;6(12):967-74
references.pmid: 18049471
references.citation: Drug Saf. 2008;31(12):1097-114
references.pmid: 19026027
references.citation: N Engl J Med. 2007 Oct 4;357(14):1450-1
references.pmid: 17914053
references.citation: N Engl J Med. 2010 May 6;362(18):1708-19
references.pmid: 20445182
references.citation: Pharmacotherapy. 2006 Jan;26(1):95-103
references.pmid: 16506351
references.citation: N Engl J Med. 2000 Jan 27;342(4):225-31
references.pmid: 10648763
references.citation: J Infect Dis. 2007 Nov 15;196(10):1493-9
references.pmid: 18008229
references.citation: Am J Manag Care. 2000 Feb;6(2):205-14
references.pmid: 10977420
references.citation: N Engl J Med. 2008 Oct 9;359(15):1555-64
references.pmid: 18799552
references.citation: Am J Psychiatry. 2007 Jun;164(6):870-6
references.pmid: 17541044
references.citation: Pediatr Infect Dis J. 2010 Jun;29(6):495-8
references.pmid: 20035245
references.citation: Antivir Ther. 1996 Jan;1(1):51-6
references.pmid: 11322259
references.citation: BMJ. 2003 Jun 7;326(7401):1235
references.pmid: 12791735
references.citation: Arch Intern Med. 2003 Jul 28;163(14):1667-72
references.pmid: 12885681
references.citation: J Infect Dis. 2010 Aug 15;202(4):563-6
references.pmid: 20594104
references.citation: Lancet. 2004 Aug 28-Sep 3;364(9436):759-65
references.pmid: 15337401
references.citation: J Virol. 1996 Dec;70(12):8391-401
references.pmid: 8970960
references.citation: Lancet. 2000 May 27;355(9218):1845-50
references.pmid: 10866439
references.citation: Antiviral Res. 2006 Jul;70(3):121-31
references.pmid: 16516984
references.citation: J R Coll Gen Pract. 1973 Jan;23(126):34-7
references.pmid: 4574716
references.citation: JAMA. 2003 Jan 8;289(2):179-86
references.pmid: 12517228
references.citation: Pediatr Int. 2004 Apr;46(2):122-5
references.pmid: 15056235
references.citation: Pediatrics. 2005 Jul;116(1):153-9
references.pmid: 15995046