What is Ribavirin?

Ribavirin (known under brand names such as Rebetol, Copegus, Ribasphere and Virazole) is an analog of guanosine and a synthetic nucleoside antiviral agent. It is a stable, white crystalline compound with a maximum solubility in water of 142 mg/mL at 25°C and only a slight solubility in alcohol. Its empirical formula is C8H12N4O5 and the molecular weight is 244.2.

In 1972, Sidwell and his colleagues first reported that ribavirin shows inhibitory effects for a wide variety of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) viruses in culture and in animals, without undue toxicity. Primary adverse reaction associated with ribavirin is hemolytic anemia, which refers to a condition in which red blood cells are destroyed faster than new ones are made.

The United States Food and Drug Administration (FDA) has approved the use of ribavirin for treatment of respiratory syncytial virus and hepatitis C virus infection. The use of combination ribavirin and interferon therapy has substantially improved rates of sustained virologic response in patients with chronic hepatitis C virus infection.

Spectrum of activity

Five distinct mechanisms are proposed to explain the antiviral properties of ribavirin. These include both direct mechanisms (polymerase inhibition, interference with RNA capping and lethal mutagenesis) and indirect mechanisms (inosine monophosphate dehydrogenase inhibition and various immunomodulatory effects). Such multiple mechanisms of action mean that viral resistance develops rarely.

A unique property of ribavirin is that it is clinically effective against unrelated viruses from diverse families. Its spectrum of activity includes respiratory tract infections due to respiratory syncytial virus and influenza, measles, herpesvirus infections, hemorrhagic fever with renal syndrome, Lassa fever and chronic hepatitis C infection.

Ribavirin was found to suppress the replication of human immunodeficiency virus (HIV) in peripheral blood lymphocytes, and was also reported to enhance the efficacy of zidovudine against HIV in vitro. In combination with midazolam, keatmine and amantadine, ribavirin was also used in the treatment of rabies. The drug is ineffective against Ebola and Marburg viruses.

Albeit much is known about biochemical effects and metabolism of ribavirin in human cells, there is still a need for further research on the precise mechanism of action of ribavirin with the various viruses. Certain derivatives of ribavirin have also shown intriguing anti-cancer activity that necessitates further exploration.

Mode of drug administration and dosage

Ribavirin can be administered to humans by aerosol, oral and intravenous routes with a range of dosing regimens in different clinical settings. The volume of distribution is extensive owing to its distribution into practically all cellular compartments via nucleoside transporters.

For the treatment of chronic hepatitis C infections, ribavirin is most commonly used in combination with pegylated interferon at a dose of 800-1200 mg daily. For the treatment of hemorrhagic fever with renal syndrome, a successful protocol starts with the loading dose of 33 mg/kg, followed by 16 mg/kg every 6 hours for four days and then 8 mg/kg every 8 hours for three more days. Similar protocol is employed for the treatment of Lassa fever.

Aerosol administration is achieved via an aerosol generator, preferably the small particle model. Final concentration should be 20 mg/ml and the drug is given at a rate of 12.5 liters of ribavirin in air per minute continuously for 12-18 hours every day up to one week.

Ribavirin for intravenous administration has also been given intraventricularly in order to treat patients with subacute sclerosing panencephalitis (also known as atypical measles virus encephalitis). An initial dose of 1 mg/kg diluted with saline is injected intraventriculary, and further dosing is dependent on cerebrospinal fluid ribavirin levels.


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Further Reading

Last Updated: Aug 23, 2018

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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