RIBAVIRIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H12N4O5
Molecular Weight	244.2047
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1=NN(C=N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O

InChI

InChIKey=IWUCXVSUMQZMFG-AFCXAGJDSA-N

InChI=1S/C8H12N4O5/c9-6(16)7-10-2-12(11-7)8-5(15)4(14)3(1-13)17-8/h2-5,8,13-15H,1H2,(H2,9,16)/t3-,4-,5-,8-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf
Curator's Comment: description was created based on several sources, including https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adf16e64-345f-469a-b987-3fbdd17e0ac2 | http://www.news-medical.net/health/Ribavirin-History.aspx

Ribavirin is a synthetic nucleoside analogue, which was first discovered and developed in 1970 by researchers from the International Chemical & Nuclear Corporation (ICN), today known as Valeant Pharmaceuticals. Ribavirin was initially approved for use in humans to treat pediatric respiratory syncytial virus infections (RSV). In cell cultures the inhibitory activity of ribavirin for RSV is selective. The mechanism of action is unknown. Reversal of the in vitro antiviral activity by guanosine or xanthosine suggests ribavirin may act as an analogue of these cellular metabolites. There were no other significant advancements in the treatment of hepatitis C until 1998, when the combination of ribavirin and interferon-alpha gained approval. Clinically, ribavirin showed a small, additive antiviral effect in combination with interferon, but its main effect was dose-dependent prevention of virological relapse. The mechanism by which the combination of ribavirin and an interferon product exerts its effects against the hepatitis C virus has not been fully established. However, it could be thorough the inhibition of inosine monophosphate dehydrogenase (IMPDH), which is the key step in de novo guanine synthesis, a requirement for viral replication.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Inosine-5'-monophosphate dehydrogenase 1 4 Target ID: CHEMBL1822 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16293677	Inhibitor 8297
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14 Target ID: CHEMBL5375 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16107837	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Respiratory syncytial virus infection 4 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adf16e64-345f-469a-b987-3fbdd17e0ac2	Primary		Approved 8429	VIRAZOLE Approved Use VIRAZOLE (Ribavirin for Inhalation Solution, USP) is indicated for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus. Treatment early in the course of severe lower respiratory tract infection may be necessary to achieve efficacy. Only severe RSV lower respiratory tract infection should be treated with VIRAZOLE. The vast majority of infants and children with RSV infection have disease that is mild, self-limited, and does not require hospitalization or antiviral treatment. Many children with mild lower respiratory tract involvement will require shorter hospitalization than would be required for a full course of VIRAZOLE aerosol (3 to 7 days) and should not be treated with the drug. Thus the decision to treat with VIRAZOLE should be based on the severity of the RSV infection. The presence of an underlying condition such as prematurity, immunosuppression or cardiopulmonary disease may increase the severity of clinical manifestations and complications of RSV infection. Use of aerosolized VIRAZOLE in patients requiring mechanical ventilator assistance should be undertaken only by physicians and support staff familiar with this mode of administration and the specific ventilator being used Launch Date 1985
Chronic hepatitis C 42 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf	Primary		Approved 8429	COPEGUS Approved Use COPEGUS in combination with PEGASYS (peginterferon alfa-2a) is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A). Launch Date 2002

C_max

Value	Dose	Co-administered	Analyte	Population
3680 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020903s052,021546s008lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RIBAVIRIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
228000 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020903s052,021546s008lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RIBAVIRIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
298 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020903s052,021546s008lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RIBAVIRIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 1 times / day multiple, oral Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33617629	unhealthy, 21 years n = 1 Health Status: unhealthy Condition: respiratory syncytial virus (RSV) infection Age Group: 21 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33617629	Disc. AE: Hyperuricemia, Injury to kidney... AEs leading to discontinuation/dose reduction: Hyperuricemia (severe, 1 patient) Injury to kidney (acute, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/33617629
2400 mg 1 times / day multiple, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: multiple Dose: 2400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2444379	unhealthy, 39.9 years (range: 27 - 51 years) n = 3 Health Status: unhealthy Condition: generalized lymphadenopathy Age Group: 39.9 years (range: 27 - 51 years) Sex: M Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/2444379	Disc. AE: Nausea, Vomiting... Other AEs: CNS disorder (NOS), Fatigue... AEs leading to discontinuation/dose reduction: Nausea (1 patient) Vomiting (1 patient) Headache (severe, 1 patient) Hematocrit low (1 patient) Other AEs: CNS disorder (NOS) (severe, 3 patients) Fatigue (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2444379
16 mg/kg 4 times / day multiple, intravenous Highest studied dose Dose: 16 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 16 mg/kg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21544005	unhealthy, 6-10 years n = 2 Health Status: unhealthy Condition: La Crosse viral encephalitis Age Group: 6-10 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/21544005	Disc. AE: Nonprotein nitrogen blood increased, Abdominal pain... AEs leading to discontinuation/dose reduction: Nonprotein nitrogen blood increased (1 patient) Abdominal pain (1 patient) Tenderness (1 patient) Anorexia (1 patient) Pancreatic enzymes increased (1 patient) Pancreatitis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/21544005
1200 mg 1 times / day multiple, oral Recommended Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf	pregnant Health Status: pregnant Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf	Other AEs: Fetal death... Other AEs: Fetal death (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf
1200 mg 1 times / day multiple, oral Recommended Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf	unhealthy Health Status: unhealthy Condition: chronic hepatitis C virus infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21511_Copegus_lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF#page=16 Page: 16.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63580	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63580
ChemicalBook	CB0689324	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0689324
MolPort	MolPort-002-507-104	https://www.molport.com/shop/molecule-link/MolPort-002-507-104
Selleck Chemicals	Ribavirin(Copegus)	http://www.selleckchem.com/products/Ribavirin(Copegus).html
ZINC	ZINC000001035331	http://zinc15.docking.org/substances/ZINC000001035331
eMolecules	1944721	https://www.emolecules.com/cgi-bin/more?vid=1944721

PubMed

Title	Date	PubMed
Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents.	1976 Feb	1249809
Effect of cytosine, arabinoside, iododeoxyuridine, ethyldeoxyuridine, thiocyanatodeoxyuridine, and ribavirin on tail lesion formation in mice infected with vaccinia virus.	1976 Mar	1257248
Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines.	1992 Aug 21	1324318
Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'-deoxyadenosine.	1992 Jun	1365816
(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.	1992 Jun 12	1319491
Synthesis and antiviral activity of some new S-adenosyl-L-homocysteine derivatives.	1992 Nov 27	1335077
[ROC curve analysis of factors predictive of response to treatment with interferon plus ribavirin in patients with chronic hepatitis C relapse after previous interferon treatment].	2002 Dec	12587043
[Novel mode of action of ribavirin (Rebetol), a drug for the treatment of chronic hepatitis C: inducting the mutation of RNA viruses].	2002 Dec	12528471
Antiviral activity of brassinosteroids derivatives against measles virus in cell cultures.	2002 Jan	12180649
Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.	2002 Jul	12093990
Synthesis and antiviral evaluation of a mutagenic and non-hydrogen bonding ribonucleoside analogue: 1-beta-D-Ribofuranosyl-3-nitropyrrole.	2002 Jul 23	12119016
Interferon-alpha induced transient thyroid dysfunction in hepatitis C.	2002 Mar	12185880
Inhibition of the replication of a hepatitis C virus-like RNA template by interferon and 3'-deoxycytidine.	2002 Nov	12718408
Inhibitors of the IMPDH enzyme as potential anti-bovine viral diarrhoea virus agents.	2002 Nov	12718406
The quest for an efficacious antiviral for respiratory syncytial virus.	2002 Nov	12718405
Search of antimicrobial activity of selected non-antibiotic drugs.	2002 Nov-Dec	12669766
Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.	2002 Oct	12367731
Treatment of acute hepatitis C virus infection with interferon-alpha 2b and ribavirin: case report and review of the literature.	2002 Oct 14	12437778
U.S. veterans' experience with rebetron in a nonstudy environment: success or failure?	2002 Sep	12358260
Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C.	2002 Sep	12197842
Meta-analysis: ribavirin-induced haemolytic anaemia in patients with chronic hepatitis C.	2002 Sep	12197841
Emotional distress during interferon-alpha-2B and ribavirin treatment of chronic hepatitis C.	2002 Sep-Oct	12297606
Anemia in the treatment of hepatitis C virus infection.	2003	14582000
Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C.	2003	12656650
Hemoglobinuria with ribavirin treatment.	2003 Apr	12642748
Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats.	2003 Apr 15	12672002
Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.	2003 Aug	12897097
Combination therapy in the treatment of chronic viral hepatitis and prevention of hepatocellular carcinoma.	2003 Aug	12860172
Synthesis of 1,2,3-triazolo-carbanucleoside analogues of ribavirin targeting an HCV in replicon.	2003 Aug 15	12901908
[Is chronic hepatitis C treatment as efficient in the general population as in randomised trials?].	2003 Aug-Sep	14586246
Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia.	2003 Feb	12713065
Posterior segment complications in patients with hepatitis C treated with interferon and ribavirin.	2003 Feb	12578794
Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups.	2003 Feb	12540795
In vitro activity of potential anti-poxvirus agents.	2003 Jan	12615301
Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.	2003 Jan	12615299
Successful treatment of giant cell hepatitis with Rebetron (interferon/ribavirin).	2003 Jan	12526974
Synergistic in vitro interactions between alpha interferon and ribavirin against bovine viral diarrhea virus and yellow fever virus as surrogate models of hepatitis C virus replication.	2003 Jul	12821481
[52-year-old patient with subcutaneous space-occupying lesion in immunosuppression].	2003 Jun	14567110
Correlation of sICAM-1 and sVCAM-1 level with biochemical, histological and viral findings in chronic hepatitis C after interferon-alpha + ribavirin therapy.	2003 Jun	12853993
Severe migraine headaches are caused by ribavirin but not by interferon alpha-2B in combination therapy for chronic hepatitis C.	2003 Jun	12763386
Ribavirin and alpha interferon enhance death receptor-mediated apoptosis and caspase activation in human hepatoma cells.	2003 Jun	12760867
A pilot study of eicosapentaenoic acid therapy for ribavirin-related anemia in patients with chronic hepatitis C.	2003 Jun	12736713
The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA.	2003 Jun 5	12781720
Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses.	2003 Mar	12719009
Two distinct phases of virus-induced nuclear factor kappa B regulation enhance tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in virus-infected cells.	2003 May 16	12637521
How can we identify better those with recurrent hepatitis C who will respond to therapy? What are the optimal treatment regimen and treatment duration?	2003 Nov	14586905
[Use of erythropoietin in the treatment of anemia induced by ribavirin/interferon in patients with hepatitis C].	2003 Oct	14568602
Rosacea fulminans associated with pegylated interferon alpha-2B and ribavirin therapy.	2003 Oct	14558405
Intracerebral haemorrhage and hepatitis C treatment.	2003 Sep	12969193
Treatment of interferon-induced psychosis in patients with comorbid hepatitis C and HIV.	2003 Sep-Oct	12954918

Patents

Sample Use Guides

In Vivo Use Guide

respiratory syncytial virus infection: 20 mg/mL VIRAZOLE (Ribavirin for inhalation solution) as the starting solution in the drug reservoir of the SPAG-2 unit, with continuous aerosol administration for 12-18 hours per day for 3 to 7 days. Using the recommended drug concentration of 20 mg/mL the average aerosol concentration for a 12 hour delivery period would be 190 micrograms/liter of air. Aerosolized VIRAZOLE should not be administered in a mixture for combined aerosolization or simultaneously with other aerosolized medications. Chronic hepatitis C virus infection: The recommended duration of treatment for patients previously untreated with ribavirin and interferon is 24 to 48 weeks. The daily dose of COPEGUS (ribavirin) tablets is 800 mg to 1200 mg administered orally in two divided doses. The dose should be individualized to the patient depending on baseline disease characteristics (eg, genotype), response to therapy, and tolerability of the regimen.

Route of Administration: Other

In Vitro Use Guide

To determine the optimal concentration and timing of ribavirin treatment for the inhibition of viral transcription, Human A549 pulmonary type II epithelial cells pretreated (2 h) or posttreated (1 h) with increasing concentrations of ribavirin (from10 to 100 microg/ml) were exposed to pRSV (Respiratory syncytial virus). Total cellular RNA was harvested 36 h later, and the abundance of the 1.1-kb RSV N transcript was measured by Northern blotting. Ribavirin treatment potently inhibited RSV transcription, thereby reducing the level of RSV N transcripts to approximately 13% of levels in nontreated cells. In RSV-infected epithelial cells, ribavirin reduces plaque formation, the release of infectious virions, and F glycoprotein expression.

Name

Type

Language

RIBAVIRIN

Official Name

English

COPEGUS

Brand Name

English

COTRONAK

Brand Name

English

RIBAVIRIN [USP MONOGRAPH]

Common Name

English

RBV

Common Name

English

ribavirin [INN]

Common Name

English

1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE, 1-.BETA.-D-RIBOFURANOSYL-

Common Name

English

RIBAVIRIN [HSDB]

Common Name

English

RIBAVIRIN [EMA EPAR]

Common Name

English

SCH 18908

Code

English

SCH-18908

Code

English

Ribavirin [WHO-DD]

Common Name

English

NSC-163039

Code

English

RIBAVIRIN BIOPARTNERS

Brand Name

English

RIBAVIRIN [MI]

Common Name

English

RIBAVIRIN TEVA PHARMA B.V.

Brand Name

English

REBETOL

Brand Name

English

RIBAVIRIN MYLAN

Brand Name

English

RIBAVIRIN [EP MONOGRAPH]

Common Name

English

RIBAVIRIN [VANDF]

Common Name

English

RIBAVIRIN [JAN]

Common Name

English

RIBAVIRIN [MART.]

Common Name

English

RIBAVIRIN [ORANGE BOOK]

Common Name

English

RIBAVIRIN COMPONENT OF PEGINTERFERON

Common Name

English

VIRAZOLE

Brand Name

English

RIBASPHERE

Brand Name

English

RIBAVIRIN [USAN]

Common Name

English

RIBAVIRIN TEVA

Brand Name

English

1-.BETA.-D-RIBOFURANOSYL-1H-1,2,4-TRIAZOLE-3-CARBOXAMIDE

Common Name

English

RIBAVIRIN [USP-RS]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175466