Ribavirin

Ribavirin is a nucleoside analog that has in vitro activity against both influenza A and B viruses. It has not been looked at in depth for influenza therapy, and human data exists mostly as aerosol treatment. It has not demonstrated anti-flu activity when given orally as monotherapy. Ribavirin is used orally in combination with standard or pegylated interferon alfa for treatment of hepatitis C (the combination improves the rate of sustained virologic clearance when compared to ribavirin monotherapy).

Ribavirin is also available as an aerosol, and has been used as a therapy for respiratory syncytial virus (RSV) in infants, a common cause of viral bronchiolitis and pneumonia. That therapy has fallen into disfavor because of inconsistent results and concerns about potential carcinogenic affects on the fetus of inhaling ribavirin when pregnant (a practical concern for respiratory therapists and nurses).

Viramidine is an active derivative and may represent a pro-drug (not licensed for clinical use in the United States as of this writing).

Recent concerns about pandemic flu have rekindled interest in the drug.

  • Nature Reviews Drug Discovery covered ribavirin in 2006 as a potential drug, noting a lack of drug generated influenza-resistance as well as the potential for intravenous as well as oral and aerosolized use.
  • WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus (Lancet Infect Dis 2007; 7: 2131) also briefly covers ribavirin:
Other recommendations
In addition to the recommendations of antiviral use, the panel evaluated other pharmacological management options but made only one detailed recommendation (strong recommendation based on very low quality evidence against the use of ribavirin in pregnancy because of known adverse effects).

The question “Should ribavirin be used?” in H5N1 therapy was specifically raised in the WHO document, though currently it’s an unanswered question. Another reference to the need for ongoing studies can be found in Chest (Chest. 2006;129:156–168.):

If the use of an increased dosage of neuraminidase inhibitors for avian influenza infection is indeed beneficial, this will have a major impact on the supply of these agents in a pandemic situation. One option is to use a combination of oseltamivir and probenecid to double the systemic exposure following a conventional dosage of oseltamivir.78 Another option is to use combination therapy with two neuraminidase inhibitors, one neuraminidase inhibitor plus one adamantane if the circulating genotype is susceptible to adamantanes, or one neuraminidase inhibitor plus ribavirin (or viramidine when it becomes available). The synergistic effects of these combinations, if any, need to be studied urgently by in vitro and animal studies. Ribavirin has been used in the treatment of human influenza A virus infections, usually administered orally or by aerosolization, and occasionally by the IV route for severe infections or in immunocompromised hosts. A consistent benefit has not been observed in clinical studies, and currently ribavirin is not considered to be a drug of choice for influenza A infection. There are only limited in vitro data on the activity of ribavirin on avian influenza viruses.73 But ribavirin was shown to be highly effective in reducing mortality in a mannan-enhanced mice model infected by influenza B even when treatment was delayed for 3 days after the infection, when oseltamivir treatment is no longer effective. Combination of oseltamivir with ribavirin treatment started at such delayed timing does not increase the efficacy in this mice model. Viramidine is a carboxamidine analog of ribavirin that also demonstrates broad-spectrum antiviral activities like ribavirin. Its anti-influenza activity has been confirmed in limited in vitro and animal studies. 73 Viramidine is currently not licensed for clinical use.

Ribavirin had issues associated with anemia and lack of efficacy when used in SARS patients, highlighting and suggesting the need for caution in the absence of clinical data:

Adverse Effects of Ribavirin and Outcome in Severe Acute Respiratory Syndrome

Conclusions: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Other resources:

  • Activities of oseltamivir and ribavirin used alone and in combination against infections in mice with recent isolates of influenza A (H1N1) and B viruses.Antivir Chem Chemother. 2006;17(4):185–92.
  • In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res. 2005 Oct;68(1):10–7.
Page last modified on February 04, 2007, at 09:24 AM by DemFromCT