title: Original research: Intravenous ribavirin--review of the FDA's Emergency Investigational New Drug Database (1997-2008) and literature review.
abstract: Intravenous (IV) ribavirin does not have US Food and Drug Administration (FDA) approval, although oral and aerosol formulations have been approved. Intravenous ribavirin can, however, be authorized for use as a result of an Emergency Investigational New Drug (EIND) application as investigational treatment for patients with serious viral infections, including emerging or rare infections for which no alternative treatment is available. This retrospective study evaluated clinical experience with IV ribavirin based on a review of the FDA's EIND database and a literature review. The main outcome measures were disease condition, clinical outcomes, and adverse events (AEs). First, the FDA's EIND database was evaluated for these variables among patients authorized to receive investigational IV ribavirin. Second, published literature on IV ribavirin was reviewed for diseases treated, reported clinical outcomes, and AEs. Adverse events reported in the literature were compared with AEs listed in approved product labeling (aerosol and oral formulations). From February 1997 to December 2008, 608 IV ribavirin EIND requests were made for 19 disease conditions. Adenovirus, respiratory syncytial virus, and parainfluenza infections comprised 84.7% of IV ribavirin EINDs. Inadequate reporting of clinical outcomes and AEs in the EIND database prevented analysis of either outcome. Data interpretation in the literature was limited by multiple factors, including retrospective design, small sample sizes, differences in reporting outcomes and AEs, lack of generalizability, and potential confounders such as concomitant medications, selection bias, and reporting bias. Reported AEs were consistent with labels of approved aerosol and oral formulations, except for lip and gingival swelling. However, estimates of frequency, severity, and causality of AEs associated with IV ribavirin could not be determined because of study limitations. Our study findings suggest that the literature is inconclusive on the potential benefit for continued use of IV ribavirin. A review of the literature and the FDA's EIND database suggests that prospective, controlled trials of IV ribavirin in patients with adenovirus, parainfluenza, or serious respiratory syncytial virus infections could be feasible.
authors.affiliation: OND/DAVP, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Riner
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Chan-Tack
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Murray
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D017277:Drug Approval / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014777:Virus Diseases / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D015507:Drugs, Investigational; D012254:Ribavirin