VIRAZOLE SUMMARY
Virazole® is a brand name for ribavirin, a synthetic nucleoside with antiviral activity. VIRAZOLE for inhalation solution is a sterile, lyophilized powder to be reconstituted for aerosol administration. Each 100 mL glass vial contains 6 grams of ribavirin, and when reconstituted to the recommended volume of 300 mL with sterile water for injection or sterile water for inhalation (no preservatives added), will contain 20 mg of ribavirin per mL, pH approximately 5.5. Aerosolization is to be carried out in a Small Particle Aerosol Generator (SPAG-2) nebulizer only.
VIRAZOLE is indicated for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus. Treatment early in the course of severe lower respiratory tract infection may be necessary to achieve efficacy.
Only severe RSV lower respiratory tract infection should be treated with VIRAZOLE. The vast majority of infants and children with RSV infection have disease that is mild, self-limited, and does not require hospitalization or antiviral treatment. Many children with mild lower respiratory tract involvement will require shorter hospitalization than would be required for a full course of VIRAZOLE aerosol (3 to 7 days) and should not be treated with the drug. Thus the decision to treat with VIRAZOLE should be based on the severity of the RSV infection.
The presence of an underlying condition such as prematurity, immunosuppression or cardiopulmonary disease may increase the severity of clinical manifestations and complications of RSV infection.
Use of aerosolized VIRAZOLE in patients requiring mechanical ventilator assistance should be undertaken only by physicians and support staff familiar with this mode of administration and the specific ventilator being used (see WARNINGS, and DOSAGE AND ADMINISTRATION).
RSV infection should be documented by a rapid diagnostic method such as demonstration of viral antigen in respiratory tract secretions by immunofluorescence3,4 or ELISA5 before or during the first 24 hours of treatment. Treatment may be initiated while awaiting rapid diagnostic test results. However, treatment should not be continued without documentation of RSV infection.
Non-culture antigen detection techniques may have false positive or false negative results. Assessment of the clinical situation, the time of year and other parameters may warrant reevaluation of the laboratory diagnosis.
Non-Mechanically-Ventilated Infants
: In two placebo controlled trials in infants hospitalized with RSV lower respiratory tract infection, aerosolized VIRAZOLE treatment had a therapeutic effect, as judged by the reduction in severity of clinical manifestations of disease by treatment day 3.3,4 Treatment was most effective when instituted within the first 3 days of clinical illness. Virus titers in respiratory secretions were also significantly reduced with VIRAZOLE in one of these original studies.4 Additional controlled studies conducted since these initial trials of aerosolized VIRAZOLE in the treatment of RSV infection have supported these data.
Mechanically-Ventilated Infants
: A randomized, double-blind, placebo controlled evaluation of aerosolized VIRAZOLE at the recommended dose was conducted in 28 infants requiring mechanical ventilation for respiratory failure caused by documented RSV infection.6 Mean age was 1.4 months (SD, 1.7 months). Seven patients had underlying diseases predisposing them to severe infection and 21 were previously normal. Aerosolized VIRAZOLE treatment significantly decreased the duration of mechanical ventilation required (4.9 vs. 9.9 days, p=0.01) and duration of required supplemental oxygen (8.7 vs 13.5 days, p=0.01). Intensive patient management and monitoring techniques were employed in this study. These included endotracheal tube suctioning every 1 to 2 hours; recording of proximal airway pressure, ventilatory rate, and F1 O2 every hour; and arterial blood gas monitoring every 2 to 6 hours. To reduce the risk of VIRAZOLE precipitation and ventilator malfunction, heated wire tubing, two bacterial filters connected in series in the expiratory limb of the ventilator (with filter changes every 4 hours), and water column pressure release valves to monitor internal ventilator pressures were used in connecting ventilator circuits to the SPAG-2.
Employing these techniques, no technical difficulties with VIRAZOLE administration were encountered during the study. Adverse events consisted of bacterial pneumonia in one case, staphyloccus bacteremia in one case and two cases of post-extubation stridor. None were felt to be related to VIRAZOLE administration.
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