[1] Despite widespread usage, it has faced scrutiny in the 21st century because of lack of proven efficacy in treating viral infections for which it has been prescribed in the past.

[6][7] Its common side effects include fatigue, headache, nausea, fever, muscle pains, and an irritable mood.

[1] Serious side effects include red blood cell breakdown, liver problems, and allergic reactions.

[1] Ribavirin is primarily used to treat chronic hepatitis C and viral hemorrhagic fevers (an orphan indication in most countries).

[11] Its efficacy for these purposes has been questioned in light of its Food and Drug Administration boxed warning against its use as monotherapy for chronic hepatitis C. Thus, it may be prescribed in the United States only as an adjunct to one or more other medications.

Its efficacy against viruses other than HCV, including those that cause viral hemorrhagic fever, has not been conclusively demonstrated.

[7][6] For chronic HCV infection, the oral (capsule or tablet) form of ribavirin is used only in combination with pegylated interferon alfa.

[25] Despite questions surrounding its efficacy, ribavirin remains the only antiviral known to be effective in treating Lassa fever.

[32][33][34][35] Ribavirin targeted eIF4E in AML patients in monotherapy and combination studies and this corresponded to objective clinical responses including complete remissions.

[34] The medication has two FDA "black box" warnings: One raises concerns that use before or during pregnancy by either sex may result in birth defects in the baby, and the other is regarding the risk of red blood cell breakdown.

[44] Ribavirin's amide group can make the native nucleoside drug resemble adenosine or guanosine, depending on its rotation.

[64] This was done by researchers from International Chemical and Nuclear Corporation including Roberts A. Smith, Joseph T. Witkovski and Roland K.

[65] It was reported that ribavirin was active against a variety of RNA and DNA viruses in culture and in animals, without undue toxicity in the context of cancer chemotherapies.

The drug was approved for investigational use against hantavirus in the United States in 1993, but the results from a non-randomized uncontrolled trial were not encouraging: 71% of recipients became anemic and 47% died.

[68] Unfortunately, it later turned out this haphazard approach was at best ineffective and at worst fatal, with many deaths attributed to SARS caused by ribavirin toxicity.

[70] Note that two natural products were already known with this imidazole riboside structure: substitution at the 5' carbon with OH results in pyrazofurin, an antibiotic with antiviral properties but unacceptable toxicity, and replacement with an amino group results in the natural purine synthetic precursor 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), which has only modest antiviral properties.