Details of the Drug

General Information of Drug (ID: DMEYLH9)

Drug Name
Ribavirin
Synonyms
ribavirin; 36791-04-5; Tribavirin; Rebetol; Virazole; Ribavirine; Copegus; Vilona; Ribamide; Ribasphere; Ribamidil; Viramid; Ribamidyl; Ribavirinum; Ribavirina; Rebetron; Varazid; RTCA; Ribavirin Capsules; Ribavirinum [INN-Latin]; Ribavirine [INN-French]; Ribavirina [INN-Spanish]; ICN-1229; Rebretron; Virazid; Ribav; 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide; DRG-0028; 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide; UNII-49717AWG6K; Ribavirin (Copegus); Copegus; Cotronak; RBV; RTC; Ravanex; Ribacine; Ribovirin; Viramide; Virazide; R 9644; SCH 18908; C-Virin; Copegus (TN); Drug: Ribavirin; KS-1104; R-964; RG-964; Rebetol (TN); Ribasphere (TN); Ribavirin [USAN:INN]; Vilona (TN); Virazole (Ribavirin) Inhalation Solution; Virazole (TN); AA-504/07617051; Ro 20-9963/000; Ro-20-9963; Ribavirin (JAN/USP/INN); 1-beta-D-Ribofuranosyl-1,2,4-triazolo-3-carboxamide; 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide; 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide; 1-beta-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide; RBI034 (2-5A antisense compound) + Ribavirin
Indication
Disease Entry ICD 11 Status REF
Hepatitis C virus infection 1E51.1 Approved [1]
Respiratory syncytial virus infection 1C80 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Therapeutic Class
Antiviral Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 244.2
Logarithm of the Partition Coefficient (xlogp) -1.8
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [6]
Bioavailability
60% of drug becomes completely available to its intended biological destination(s) [7]
Clearance
The drug present in the plasma can be removed from the body at the rate of 5.2 mL/min/kg [8]
Elimination
17% of drug is excreted from urine in the unchanged form [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 45 hours [8]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 35.1 micromolar/kg/day [9]
Unbound Fraction
The unbound fraction of drug in plasma is 1% [8]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 14 L/kg [8]
Water Solubility
The ability of drug to dissolve in water is measured as 142 mg/mL [6]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Hepatic function abnormal Not Available EGFR OTAPLO1S [10]
Hepatic function abnormal Not Available HGF OTGHUA23 [10]
Hepatic function abnormal Not Available HP OTGUGAF9 [10]
Chemical Identifiers
Formula
C8H12N4O5
IUPAC Name
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide
Canonical SMILES
C1=NC(=NN1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)C(=O)N
InChI
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
InChIKey
IWUCXVSUMQZMFG-AFCXAGJDSA-N
Cross-matching ID
PubChem CID
37542
ChEBI ID
CHEBI:63580
CAS Number
36791-04-5
DrugBank ID
DB00811
TTD ID
D0H3WI
VARIDT ID
DR00176
INTEDE ID
DR1413
ACDINA ID
D00589
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [11]
HUMAN inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TT3GRLK IMDH1_HUMAN Inhibitor [3]
HUMAN inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) TTTU6X1 IMDH2_HUMAN Inhibitor [3]
MERS-CoV RNA-directed RNA polymerase (RdRp) TTOA6YT R1AB_CVEMC (4378-5310) Inhibitor [5]
SARS-CoV RNA-directed RNA polymerase (RdRp) TTKXI53 R1AB_CVHSA (4370-5301) Inhibitor [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [12]
Concentrative nucleoside transporter 2 (SLC28A2) DT82KPY S28A2_HUMAN Substrate [13]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [14]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [15]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Purine nucleoside phosphorylase (PNP) DE2WSAL PNPH_HUMAN Substrate [16]
Cytosolic 5'-nucleotidase II (NT5C2) DE1DOKJ 5NTC_HUMAN Substrate [17]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alpha-actinin-2 (ACTN2) OT9FOLD7 ACTN2_HUMAN Gene/Protein Processing [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [19]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [18]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Gene/Protein Processing [20]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Drug Response [10]
Equilibrative nucleoside transporter 1 (SLC29A1) OTLOOZZS S29A1_HUMAN Regulation of Drug Effects [21]
Equilibrative nucleoside transporter 3 (SLC29A3) OTGLX8XU S29A3_HUMAN Regulation of Drug Effects [22]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Gene/Protein Processing [23]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Gene/Protein Processing [24]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Post-Translational Modifications [25]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ribavirin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Mercaptopurine DMTM2IK Major Decreased metabolism of Ribavirin caused by Mercaptopurine mediated inhibition of non-CYP450 enzyme. Mature B-cell lymphoma [2A85] [26]
Azathioprine DMMZSXQ Major Decreased metabolism of Ribavirin caused by Azathioprine mediated inhibition of non-CYP450 enzyme. Transplant rejection [NE84] [26]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 1 E00263 19700 Colorant
FD&C blue no. 2 E00446 2723854 Colorant
Isopropyl alcohol E00070 3776 Antimicrobial preservative; Solvent
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Ammonia E00007 222 Alkalizing agent
Butyl alcohol E00011 263 Flavoring agent; Solvent
Carmellose sodium E00625 Not Available Disintegrant
Crospovidone E00626 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Water E00035 962 Solvent
⏷ Show the Full List of 26 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Ribavirin 200 mg tablet 200 mg Oral Tablet Oral
Ribavirin 400 mg tablet 400 mg Oral Tablet Oral
Ribavirin 600 mg tablet 600 mg Oral Tablet Oral
Ribavirin 200 mg capsule 200 mg Oral Capsule Oral
Ribavirin 500 mg tablet 500 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 Ribavirin FDA Label
3 Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets. Nature. 2020 May 14. doi: 10.1038/s41586-020-2332-7.
4 SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 BDDCS applied to over 900 drugs
7 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
8 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
10 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
11 Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13.
12 Effects of dipyridamole coadministration on the pharmacokinetics of ribavirin in healthy volunteers. Drug Metab Pharmacokinet. 2013;28(5):406-10.
13 Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians. Pharmacogenet Genomics. 2007 Sep;17(9):783-6.
14 Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes. Biophys Chem. 2010 Mar;147(1-2):59-65.
15 Transport of levovirin prodrugs in the human intestinal Caco-2 cell line. J Pharm Sci. 2006 Jun;95(6):1318-25.
16 Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism. Drug Metab Pharmacokinet. 2014;29(2):211-4.
17 Phosphorylation of ribavirin and viramidine by adenosine kinase and cytosolic 5'-nucleotidase II: Implications for ribavirin metabolism in erythrocytes. Antimicrob Agents Chemother. 2005 Jun;49(6):2164-71.
18 Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
19 Ribavirin and alpha interferon enhance death receptor-mediated apoptosis and caspase activation in human hepatoma cells. Antimicrob Agents Chemother. 2003 Jun;47(6):1912-21. doi: 10.1128/AAC.47.6.1912-1921.2003.
20 Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation. Toxicol Appl Pharmacol. 2021 Mar 15;415:115450. doi: 10.1016/j.taap.2021.115450. Epub 2021 Feb 9.
21 Characterization of ribavirin uptake systems in human hepatocytes. J Hepatol. 2010 Apr;52(4):486-92.
22 Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22.
23 Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia. Antivir Ther. 2003 Feb;8(1):57-63.
24 Ribavirin inhibits the growth and ascites formation of hepatocellular carcinoma through downregulation of type I CARM1 and type II PRMT5. Toxicol Appl Pharmacol. 2022 Jan 15;435:115829. doi: 10.1016/j.taap.2021.115829. Epub 2021 Dec 14.
25 Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
26 Canadian Pharmacists Association.