title: Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza.
abstract: Influenza is an important cause of hospitalization due to lower respiratory tract involvement for which there is no specific antiviral treatment with proven efficacy. We conducted a double-blind, randomized, placebo-controlled trial to assess the tolerability and efficacy of nebulized zanamivir (16 mg four times a day) in combination with rimantadine compared to rimantadine with nebulized saline for treating influenza in adults hospitalized with influenza. Twenty patients tolerated the inhaled zanamivir (ZNV) plus rimantadine without decline in peak expiratory flow rates compared to the 21 who received inhaled saline. The study was terminated early because the approval of ZNV made further enrollment untenable. No significant differences were observed in the proportion of patients shedding virus by treatment day 3 (57% ZNV plus rimantadine, 67% placebo plus rimantadine), or in the durations of hospitalization and supplemental oxygen use. More ZNV plus rimantadine recipients exhibited no or mild cough on day 3 of treatment (94 vs 55%, P=0.01). Two rimantadine-resistant viruses emerged during rimantadine monotherapy; no ZNV resistance was observed. Nebulized ZNV appears to be well tolerated in this hospitalized population but further studies are needed to assess its efficacy.
authors.affiliation: University of Virginia, Charlottesville, Va., USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ison
authors.forename: John W
authors.initials: JW
authors.lastname: Gnann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nagy-Agren
authors.forename: John
authors.initials: J
authors.lastname: Treannor
authors.forename: Carlos
authors.initials: C
authors.lastname: Paya
authors.forename: Roy
authors.initials: R
authors.lastname: Steigbigel
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006146:Guanidines; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011714:Pyrans; D012138:Respiratory Therapy / Q000379:methods; D012299:Rimantadine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012794:Sialic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D053243:Zanamivir
chemical_list: D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D012299:Rimantadine; D053243:Zanamivir