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Ribavirin May Be Treatment of Choice for Severe Acute Respiratory Syndrome, For Now

Ribavirin, a nucleoside analogue, may be enjoying a resurgence in popularity due to its potential as a treatment for severe acute respiratory syndrome (SARS).

Traditionally used as treatment for respiratory syncytial virus and - in combination with interferon alpha2b - for hepatitis C , emerging data on ribavirin's potential for treatment or prevention of SARS were published today in an early release of the Canadian Medical Association Journal.

Lead author Dr. Gideon Koren of the Hospital for Sick Children, Toronto, Ontario, Canada writes that it is likely ribavirin will be the recommended treatment choice for now. Available in intravenous, oral and aerosol formulations, parenteral ribavirin is not approved for sale in Canada, however, but can be obtained through the Special Access Programme.

Recent reports from Hong Kong and Canada describe the results of ribavirin use. In Toronto, of 7 patients treated on the currently prescribed dosing regimen for haemorrhagic fever viruses, 1 died, 1 was placed on mechanical ventilation and 5 improved within 5 days. It should be noted that those who improved were treated more aggressively. Of these 5, 3 have recovered completely, and 2 had mild dyspnoea at 3-week follow up.

In Hong Kong, 10 patients received ribavirin treatment, 9 intravenously (IV) and 1 orally. All patients also received 1 of 2 corticosteroids, hydrocortisone or methylprednisolone. Median treatment length was 12.5 days (range, 3 to 22 days) after onset of symptoms. Eight patients showed improvement within 2 days, while 2 patients died.

Initial recommended treatment is IV administration, adjusted for creatinine clearance. For adult patients with creatinine clearance of more than 60 mL/minute, the dose should be 400 mg IV every 8 hours for 3 days, followed by oral ribavirin 1200 mg twice a day for 7 days. Oral ribavirin should be taken with food.

For those whose creatinine clearance is between 30 and 60 mL/minute, the daily dose is reduced by 50% (300 mg IV every 12 hours for 3 days, followed by 600 mg orally twice a day for 7 days). Patients whose creatinine clearance is less than 30 mL/minute should have the dose reduced by 75% of the initial recommendation (300 mg IV every 24 hours for 3 days, followed by 600 mg orally for 3 days).

Earlier dosage recommendations had been higher but in vitro efficacy against SARS was not supported.

Recommended paediatric dosages for probable or suspected SARS are: a one-time loading dose of 33 mg/kg IV (maximum of 2 g/dose), followed 6 hours later by 16 mg/kg IV every 6 hours for 4 days (maximum 1 g/dose). Eight hours following the last 16 mg/kg dose, the drug is then tapered to 8 mg/kg (maximum 500 mg/dose) every 8 hours for 3 to 6 days. Ribavirin can also be administered via aerosol: 20 mg/ml for 18 hours per day or 60 mg/mL every eight hours for a total of six hours administration per day.

Some investigators believe, however, that administering aerosol drugs may increase the chances of spreading the disease. For instance, in an article published April 15 in the New York Times, Dr. Susan C. Baker, a professor of microbiology at Loyola University of Chicago, was quoted as saying, "You put someone with a viral infection in their lungs on a nebulizer. . . you're going to spread the disease". This was in reference to a patient in Hong Kong who spread SARS to 112 others, including all the doctors and nurses who treated him, who received aerosolized treatment.

Ribavirin should be avoided or modified for pregnant women or those of child-bearing potential, patients who have comorbid illnesses, renal insufficiency, or demonstrated hypersensitivity to the drug.

Adverse reactions to ribavirin aerosol include nausea, headaches, rash, conjunctivitis, and opacities of contact lenses. Rarely, exacerbation of bronchospasm could occur in either patients or exposed caregivers. Some adverse reactions to oral or IV ribavirin include reversible dose-dependant anaemia and bone marrow suppression, haemolytic anaemia, deteriorating cardiac status in patients with pre-existing cardiac disease, and electrolyte disturbances.
CMAJ 2003;168:10:7-10.

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