Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome.
OBJECTIVE
To distinguish adverse events related to ribavirin therapy from those attributable to severe acute respiratory syndrome (SARS), and to determine the rate of potential ribavirin-related adverse events.


METHODS
Retrospective cohort study.


METHODS
Hospitals in Toronto, Ontario, Canada.


METHODS
A cohort of 306 patients with confirmed or probable SARS, 183 of whom received ribavirin and 123 of whom did not, between February 23, 2003, and July 1, 2003. Of the 183 treated patients, 155 (85%) received very high-dose ribavirin; the other 28 treated patients received lower-dose regimens.


RESULTS
Data on all patients with SARS admitted to hospitals in Toronto were abstracted from charts and electronic databases onto a standardized form by trained research nurses. Logistic regression was used to evaluate the association between ribavirin use and each adverse event (progressive anemia, hypomagnesemia, hypocalcemia, bradycardia, transaminitis, and hyperamylasemia) after adjusting for SARS-related prognostic factors and corticosteroid use. In the primary logistic regression analysis, ribavirin use was strongly associated with anemia (odds ratio [OR] 3.0, 99% confidence interval [CI] 1.5-6.1, p<0.0001), hypomagnesemia (OR 21, 99% CI 5.8-73, p<0.0001), and bradycardia (OR 2.3, 99% CI 1.0-5.1, p=0.007). Hypocalcemia, transaminitis, and hyperamylasemia were not associated with ribavirin use. The risk of anemia, hypomagnesemia, and bradycardia attributable to ribavirin use was 27%, 45%, and 17%, respectively.


CONCLUSIONS
High-dose ribavirin is associated with a high rate of adverse events. The use of high-dose ribavirin is appropriate only for the treatment of infectious diseases for which ribavirin has proven clinical efficacy, or in the context of a clinical trial. Ribavirin should not be used empirically for the treatment of viral syndromes of unknown origin.
Muller
Matthew P
MP
Department of Microbiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. mmuller@mtsinai.on.ca
Dresser
Linda
L
Raboud
Janet
J
McGeer
Allison
A
Rea
Elizabeth
E
Richardson
Susan E
SE
Mazzulli
Tony
T
Loeb
Mark
M
Louie
Marie
M
D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001919:Bradycardia / Q000139:chemically induced; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D004196:Disease Outbreaks; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008275:Magnesium Deficiency / Q000139:chemically induced; D008297:Male; D016347:Medical Records Systems, Computerized / Q000706:statistics & numerical data; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D013746:Tetany / Q000139:chemically induced; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000998:Antiviral Agents; D012254:Ribavirin