RIBAVIRINE BEKER

Producing a broad-spectrum activity against several RNA and DNA viruses, Ribavirin is a synthetic guanosine nucleoside and antiviral agent that interferes with the synthesis of viral mRNA.

It is primarily indicated for use in treating hepatitis C and viral hemorrhagic fevers.

HCV is a single-stranded

RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 9.

It is reported that ribavirin might be only effective in early stages of viral hemorrhagic fevers including Lasser fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection.

Ribavirin is a prodrug that is metabolized into nucleoside analogs that blocks viral RNA synthesis and viral mRNA capping.

Before the development of newer drugs, ribavirin and Peginterferon alfa-2a / Peginterferon alfa-2b dual therapy was considered the first-generation and standard antiviral treatment 5.

The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype and 3 5.

Newer drugs developed as Hepatitis

C viral infection treatments can be used to reduce or eliminate the use of ribavirin, which are associated with serious adverse effects.

They also improve therapeutic efficacy in patients with failed Peginterferon alfa-2a / Peginterferon alfa-2b and ribavirin-based therapy.

The potential use of ribavirin as a treatment for acute myeloid leukemia is currently under investigation.

According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), ribavirin is typically used as an adjunct therapy to various first-line and second-line combination therapies recommended for each genotypes.

Ribavirin is added to decrease relapse rates by accelerating viral clearance early in the treatment course 7.

When used to treat Hepatitis

C virus (HCV) infections, it is always used as a part of combination therapies as ribavirin monotherapy is not efficacious in the treatment of chronic hepatitis C infection 6.

Additionally, including ribavirin in the regimen can increase the risk of anemia.

In HCV genotye 1/2/3/4/5/6 patients, ribavirin can be used in combination therapy involving Daclatasvir and Sofosbuvir, Eplusa ( Sofosbuvir, Velpatasvir ), Harvoni ( Sofosbuvir, Ledipasvir ), Simeprevir and Sofosbuvir, Viekira Pak ( Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir ), Technivie ( Ritonavir, Ombitasvir, Paritaprevir ) and Zepatier ( Elbasvir, Grazoprevir ).

Addition of weight-based ribavirin to

Technivie therapy increased sustained virologic response after 12 weeks of daily therapy (SVR12) from 90% to 97% in patients with HCV genotype 1a and 90.9% to 100% in HCV genotype 4 patients 9.

Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients.

Combination therapy of ribavirin and

Peginterferon alfa-2a results in the SVR of 44% in patients with genotype 1 infection and 70% in patients with genotype 2-6.

The inclusion of ribavirin in the combination therapies depend on individual patient's profile, for example if HCV genotype 3 patient has a Y93H genetic variant and compensated cirrhosis.

Indicated for the treatment of chronic Hepatitis C virus (HCV) infection in combination with other antiviral agents with the intent to cure or achieve a sustained virologic response (SVR).

Typically added to improve

SVR and reduce relapse rates 6.

The addition of ribavirin in Technivie therapy indicated for treating HCV genotype 1a and 4 infections is recommended in patients with or without cirrhosis.

Resistance: viral genetic determinants resulting in variable response to ribavirin therapy has not been yet determined.

Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses.

It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material.

The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules.

Inosine-5'-monophosphate dehydrogenase 1 Inhibitor RNA-directed RNA polymerase L (HPIV-2) Antagonist Genome polyprotein (DENV-2) Inhibitor + 1 more target.

Ribavirin is reported to be rapidly and extensively absorbed following oral administration.

The average time to reach

Cmax was 2 hours after oral administration of 1200 mg ribavirin Label.

The oral bioavailability is 64% following a single oral dose administration of 600 mg ribavirin 10.

Ribavirin displays a large volume of distribution Label.

First and as a step required for activation, ribavirin is phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites.

After activation and function, ribavirin undergoes two metabolic pathways where it is reversibly phosphorlyated or degraded via deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite.

In vitro studies indicate that ribavirin is not a substrate of CYP450 enzymes 10.

The metabolites of ribavirin are renally excreted.

After the oral administration of 600 mg radiolabeled ribavirin, approximately 61% of the drug was detected in the urine and 12% was detected in the feces. 17% of administered dose was in unchanged form 10.

The terminal half-life of ribavirin following administration of a single oral dose of 1200 mg is about 120-170 hours Label.

The total apparent clearance rate after a single oral dose administration of 1200 mg ribavirin is 26 L/h Label.

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Alfa-2A dual therapy is associated with flu-like symptoms, depression, suicide, insomnia, irritability, relapse of drug abuse/overdose, hepatic decompensation in 2% of HIV co-infected patients and bacterial infections each occurring at a frequency of less than 1%.

Ribavirin-induced anemia is a dose-dependent adverse effect where reduced hemoglobin levels can be seen within the first 1-2 weeks in therapy.

The mechanism of ribavirin-induced anemia has been shown to involve reductions in reticulocyte counts and erythrocyte Na-K pump activity, and increases in K-Cl cotransport, membrane bound IgG, and C3, and erythrocyte band 3 6.

LD50 in rats is 2700 mg/kg.