Recommended Topic Related To:

Virazole

"Dec. 3, 2012 -- The U.S. flu season is here -- the earliest start since the "moderately severe" season of 2003.

Just as in 2003, the nasty H3N2 flu bug is causing most cases so far.

"This could be a bad flu year," warned CDC"...

Virazole

Virazole

CLINICAL PHARMACOLOGY

Mechanism of Action

In cell cultures the inhibitory activity of ribavirin for respiratory syncytial virus (RSV) is selective. The mechanism of action is unknown. Reversal of the in vitroantiviral activity by guanosine or xanthosine suggests ribavirin may act as an analogue of these cellular metabolites.

Microbiology

Rfvavirin has demonstrated antiviral activity against RSV in vitro and in experimentally infected cotton rats.2 Several clinical isolates of RSV were evaluated for ribavirin susceptibility by plaque reduction in tissue culture. Plaques were reduced 85-98% by 16 µg/mL; however, results may vary with the test system. The development of resistance has not been evaluated in vitro or in clinical trials.

In addition to the above, ribavirin has been shown to have in vitro activity against influenza A and B viruses and herpes simplex virus, but the clinical significance of these data is unknown.

Immunologic Effects

Neutralizing antibody responses to RSV were decreased in aerosolized VIRAZOLE (ribavirin) treated infants compared to placebo treated infants.3 One study also showed that RSV-specific IgE antibody in bronchial secretions was decreased in patients treated with aerosolized VIRAZOLE. In rats, ribavirin administration resulted in lymphoid atrophy of the thymus, spleen and lymph nodes. Humoral immunity was reduced in guinea pigs and ferrets. Cellular immunity was also mildly depressed in animal studies. The clinical significance of these observations is unknown.

Pharmacokinetics

Assay for VIRAZOLE (ribavirin) in human materials is by a radio immunoassay which detects ribavirin and at least one metabolite.

VIRAZOLE brand of ribavirin, when administered by aerosol, is absorbed systemically. Four pediatric patients inhaling VIRAZOLE (ribavirin) aerosol administered by face mask for 2.5 hours each day for 3 days had plasma concentrations ranging from 0.44 to 1.55 fJM, with a mean concentration of 0.76 µM. The plasma half-life was reported to be 9.5 hours. Three pediatric patients inhaling aerosolized VIRAZOLE (ribavirin) administered by face mask or mist tent for 20 hours each day for 5 days had plasma concentrations ranging from 1.5 to 14.3 µM, with a mean concentration of 6.8 µM.

The bioavailability of aerosolized VIRAZOLE (ribavirin) is unknown and may depend on the mode of aerosol delivery. After aerosol treatment, peak plasma concentrations of ribavirin are 85% to 98% less than the concentration that reduced RSV plaque formation in tissue culture. After aerosol treatment, respiratory tract secretions are likely to contain ribavirin in concentrations many fold higher than those required to reduce plaque formation. However, RSV is an intracellular virus and it is unknown whether plasma concentrations or respiratory secretion concentrations of the drug better reflect intracellular concentrations in the respiratory tract.

In man, rats, and rhesus monkeys, accumulation of ribavirin and/or metabolites in the red blood cells has been noted, plateauing in red cells in man in about 4 days and gradually declining with an apparent half-life of 40 days (the half-life of erythrocytes). The extent of accumulation of ribavirin following inhalation therapy is not well defined.

Animal Toxicology

Ribavirin, when administered orally or as an aerosol, produced cardiac lesions in mice, rats, and monkeys, when given at doses of 30,36 and f 20 mg/kg or greater for 4 weeks or more (estimated human equivalent doses of 4.8,12.3 and 111.4 mg/kg for a 5 kg child, or 2.5,5.1 and 40 mg/kg for a 60 kg adult, based on body surface area adjustment). Aerosolized ribavirin administered to developing ferrets at 60 mg/kg for 10 or 30 days resulted in inflammatory and possibly emphysematous changes in the lungs. Proliferative changes were seen in the lungs following exposure at 131 mg/kg for 30 days. The significance of these findings to human administration is unknown.

Description of Studies

Non-Mechanlcally-Ventllated Infants: In two placebo controlled trials in infants hospitalized with RSV lower respiratory tract infection, aerosolized VIRAZOLE (ribavirin) treatment had a therapeutic effect, as judged by the reduction in severity of clinical manifestations of disease by treatment day 3.3, < 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 (ribavirin) in one of these original studies.4 Additional controlled studies conducted since these initial trials of aerosolized VIRAZOLE (ribavirin) in the treatment of RSV infection have supported these data.

Mechanically-Ventilated Infants: A randomized, double-blind, placebo controlled evaluation of aerosolized VIRAZOLE (ribavirin) at the recommended dose was conducted in 28 infants requiring mechanical ventilation for respiratory failure caused by documented RSV infection.8 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 (ribavirin) 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 F102 every hour; and arterial blood gas monitoring every 2 to 6 hours. To reduce the risk of VIRAZOLE (ribavirin) 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 (ribavirin) administration were encountered during the study. Adverse events consisted of bacterial pneumonia in one case, staphyloma bacteremia in one case and two cases of post-extubation stridor. None were felt to be related to VIRAZOLE (ribavirin) administration.

REFERENCES

1. Hruska JF, Bernstein JM, Douglas Jr., RG, and Hall CB. Effects of Virazole (ribavirin) on respiratory syncytial virus in vitro. Antimicrob Agents Chemother 17:770-775,1 1980.

2. Hruska JF, Morrow PE, Suffin SC, and Douglas Jr., RG. In vivo inhibition of respiratory syncytial virus by Virazole (ribavirin) . Antimicrob Agents Chemother 21:125-130,1982.

3. Taber LH, Knight V, Gilbert BE, McClung HW et al. Virazole (ribavirin) aerosol treatment of bronchiolitis associated with respiratory tract infection in infants. Pediatrics 72:613-618,1983.

Last reviewed on RxList: 1/26/2009
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Living Better

Find the secrets to longer life.

Related Drugs
Health Resources
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations