Peringatan Keamanan

Rivabirin and PEG-Interferon 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 A19644.
Oral LD50 in rats is 2700 mg/kg. Intraperitoneal LD50 in mouse is 1300 mg/kg. Potential carcinogenic effects of ribavirin to humans cannot be yet excluded as it demonstrates mutagenic activity in the in vitro mouse lymphoma assay.

Ribavirin

DB00811

small molecule approved

Deskripsi

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 L852. 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 DB00008/DB00022 dual therapy was considered the first-generation and standard antiviral treatment A19626. The dual therapy was administered for 48 weeks in patients with genotype 1, 4, 5, and 6, and 24 weeks in patients with genotype 2 and 3 A19626. 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 DB00008/DB00022 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 A19645. 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 A19644. 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 DB09102 and DB08934, Eplusa (DB08934, DB11613), Harvoni (DB08934, DB09027), DB06290 and DB08934, Viekira Pak (DB09296, DB09297, DB00503, DB09183), Technivie (DB00503, DB09296, DB09297) and Zepatier (DB11574, DB11575). 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 L852. Zepatier therapy along with ribavirin improved SVR in HCV genotype 5 patients. Combination therapy of ribavirin and DB00008 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.

Struktur Molekul 2D

Berat 244.2047
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life of ribavirin following administration of a single oral dose of 1200 mg is about 120 to 170 hours [FDA Label].
Volume Distribusi Ribavirin displays a large volume of distribution [FDA Label].
Klirens (Clearance) The total apparent clearance rate after a single oral dose administration of 1200 mg ribavirin is 26L/h [FDA Label].

Absorpsi

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 FDA Label. The oral bioavailability is 64% following a single oral dose administration of 600mg ribavirin L11019.

Metabolisme

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 L11019.

Rute Eliminasi

The metabolites of ribavirin are renally excreted. After the oral administration of 600mg 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 L11019.

Farmakogenomik

1 Varian
IFNL3 (rs12979860)

Patients with this genotype in IFNL3 have a reduced likelihood of achieving sustained virologic response to ribavirin therapy.

Interaksi Makanan

2 Data
  • 1. Avoid alcohol. Ribavirin is used to treat chronic hepatitis C infection; ingesting alcohol may worsen this infection.
  • 2. Take with food. Taking ribavirin with a high-fat meal slows the absorption and increases the AUC and Cmax of ribavirin.

Interaksi Obat

753 Data
Interferon alfa-n3 The risk or severity of anemia can be increased when Interferon alfa-n3 is combined with Ribavirin.
Interferon alfa-2a The risk or severity of anemia can be increased when Interferon alfa-2a is combined with Ribavirin.
Interferon alfacon-1 The risk or severity of anemia can be increased when Interferon alfacon-1 is combined with Ribavirin.
Interferon alfa-2b The risk or severity of anemia can be increased when Interferon alfa-2b is combined with Ribavirin.
Entecavir Ribavirin may increase the hepatotoxic activities of Entecavir.
Stavudine Ribavirin may increase the hepatotoxic activities of Stavudine.
Lamivudine Ribavirin may increase the hepatotoxic activities of Lamivudine.
Emtricitabine Ribavirin may increase the hepatotoxic activities of Emtricitabine.
Zalcitabine Ribavirin may increase the hepatotoxic activities of Zalcitabine.
Abacavir Ribavirin may increase the hepatotoxic activities of Abacavir.
Telbivudine Ribavirin may increase the hepatotoxic activities of Telbivudine.
Adefovir Ribavirin may increase the hepatotoxic activities of Adefovir.
Tenofovir Ribavirin may increase the hepatotoxic activities of Tenofovir.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Ribavirin.
Azathioprine The serum concentration of the active metabolites of Azathioprine can be increased when Azathioprine is used in combination with Ribavirin.
Didanosine The serum concentration of dideoxyadenosine 5’-triphosphate, an active metabolite of Didanosine, can be increased when used in combination with Ribavirin.
Cyclosporine Cyclosporine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Atazanavir Atazanavir may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Ribavirin which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Ribavirin which could result in a higher serum level.

Target Protein

Inosine-5'-monophosphate dehydrogenase 1 IMPDH1
RNA-directed RNA polymerase L L
Genome polyprotein
Inosine-5'-monophosphate dehydrogenase 2 IMPDH2
RNA-directed RNA polymerase catalytic subunit PB1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 16087250
    Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF: In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res. 2005 Oct;68(1):10-7.
  • PMID: 4340949
    Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK: Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(4050):705-6.
  • PMID: 16970600
    Alvarez D, Dieterich DT, Brau N, Moorehead L, Ball L, Sulkowski MS: Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons. J Viral Hepat. 2006 Oct;13(10):683-9.
  • PMID: 16123681
    Bani-Sadr F, Carrat F, Pol S, Hor R, Rosenthal E, Goujard C, Morand P, Lunel-Fabiani F, Salmon-Ceron D, Piroth L, Pialoux G, Bentata M, Cacoub P, Perronne C: Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):47-52.
  • PMID: 25585348
    Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13.
  • PMID: 18565019
    Martin P, Jensen DM: Ribavirin in the treatment of chronic hepatitis C. J Gastroenterol Hepatol. 2008 Jun;23(6):844-55. doi: 10.1111/j.1440-1746.2008.05398.x.
  • PMID: 21960835
    Te HS, Randall G, Jensen DM: Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (N Y). 2007 Mar;3(3):218-25.
  • PMID: 2546248
    Huggins JW: Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S750-61.

Contoh Produk & Brand

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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