What is Ribavirin?

Ribavirin, which is also known under its numerous brand names such as Rebetol, Copegus, Ribasphere, and Virazole, is an analog of guanosine and a synthetic nucleoside antiviral agent.

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What is ribavirin?

It is a stable, white crystalline compound with a maximum solubility in water of 142 milligrams (mg)/ milliliters (mL) at 25°C and only slight solubility in alcohol. The empirical formula of ribavirin is C8H12N4O5 and has a molecular weight of 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. The primary adverse reaction associated with ribavirin is hemolytic anemia, which refers to a condition in which red blood cells (RBCs) are destroyed faster than new ones are made.

The United States Food and Drug Administration (FDA) has approved ribavirin for the treatment of respiratory syncytial virus and hepatitis C virus infection. The use of the combination of 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 have been proposed to explain the antiviral properties of ribavirin. These include both direct and indirect mechanisms. Whereas the direct mechanisms include polymerase inhibition, interference with RNA capping, and lethal mutagenesis, the indirect mechanisms include inosine monophosphate dehydrogenase inhibition and various immunomodulatory effects. The existence of these multiple mechanisms of action indicates that viral resistance to ribavirin is a rare occurrence.

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, herpes virus infections, hemorrhagic fever with renal syndrome, Lassa fever, and chronic hepatitis C infection.

Ribavirin has also been 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, ketamine, and amantadine, ribavirin has also been used in the treatment of rabies. Notably, ribavirin is ineffective against the Ebola and Marburg viruses.

Albeit much is known about the 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 these different 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 ribavirin 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. A similar protocol is employed for the treatment of Lassa fever.

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

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


Further Reading

Last Updated: Dec 22, 2022

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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