Peringatan Keamanan

Based on single-dose toxicity studies, the lethal dose for oral and intravenous favipiravir in mice is estimated to be >2000 mg/kg.L12075 In rats, the lethal dose for oral administration is >2000 mg/kg, while the lethal dose in dogs and monkeys is >1000 mg/kg.L12075 Symptoms of overdose appear to include but are not limited to reduced body weight, vomiting, and decreased locomotor activity.L12075

In repeat-dose toxicity studies involving dogs, rats, and monkeys, notable findings after administration of oral favipiravir included: adverse effects on hematopoietic tissues such as decreased red blood cell (RBC) production, and increases in liver function parameters such as aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin, and increased vacuolization in hepatocytes.L12075 Testis toxicity was also noted.L12075

Favipiravir is known to be teratogenic; therefore, administration of favipiravir should be avoided in women if pregnancy is confirmed or suspected.A191688,A192066

Toxicity information regarding favipiravir in humans is not readily available.

Favipiravir

DB12466

small molecule approved investigational

Deskripsi

Discovered by Toyama Chemical Co., Ltd. in Japan, favipiravir is a modified pyrazine analog that was initially approved for therapeutic use in resistant cases of influenza.A191688,A191721 The antiviral targets RNA-dependent RNA polymerase (RdRp) enzymes, which are necessary for the transcription and replication of viral genomes.A191688,A191772,A191775

Not only does favipiravir inhibit replication of influenza A and B, but the drug has shown promise in the treatment of avian influenza, and may be an alternative option for influenza strains that are resistant to neuramidase inhibitors.A191721,L12090 Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19.A191724,A191958,A191961

Struktur Molekul 2D

Berat 157.104
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life of favipiravir is estimated to range from 2 to 5.5 hours.[A191721]
Volume Distribusi The apparent volume of distribution of favipiravir is 15 - 20 L.[A191727]
Klirens (Clearance) The recommended oral dosing regimen for favipiravir is as follows: Day 1: 1600 mg twice daily; Days 2-5: 600 mg twice daily.[L12075] The reported CL/F for favipiravir 1600 mg dosed once daily is 2.98 L/hr ±0.30 and the CL/F values for favipiravir 600 mg dosed twice daily on days 1-2 and once daily on days 3-7 were 6.72 L/hr ±1.68 on Day 1, and 2.89 L/hr ±0.91 on Day 7.[L12075] There is currently no reported clearance data for favipiravir 1600 mg dosed twice daily.

Absorpsi

The bioavailability of favipiravir is almost complete at 97.6%.L12075 The mean Cmax for the recommended dosing schedule of favipiravir is 51.5 ug/mL.L12075 Studies comparing the pharmacokinetic effects of multiple doses of favipiravir in healthy American and Japanese subjects are below: Japanese subjects First Dose: Cmax = 36.24 ug/mL tmax = 0.5 hr AUC = 91.40 ugxhr/mL American subjects First Dose: Cmax = 22.01 ug/mL tmax = 0.5 hr AUC = 44.11 ugxhr/mL Japanese Subjects Final Dose: Cmax = 36.23 ug/mL Tmax = 0.5 hr AUC = 215.05 ugxhr/mL American Subjects Final Dose: Cmax = 23.94 ug/mL Tmax = 0.6 hr AUC = 73.27 ugxhr/mL When favipiravir was given as a single dose of 400 mg with food, the Cmax decreased.L12075 It appears that when favipiravir is given at a higher dose or in multiple doses, irreversible inhibition of aldehyde oxidase (AO) occurs and the effect of food on the Cmax is lessened.L12075

Metabolisme

Favipiravir is extensively metabolized with metabolites excreted mainly in the urine.A191724 The antiviral undergoes hydroxylation primarily by aldehyde oxidase and to a lesser extent by xanthine oxidase to the inactive metabolite, T705M1.A191724

Rute Eliminasi

Favipiravir's metabolites are predominantly renally cleared.A191721

Interaksi Obat

377 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Favipiravir.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Favipiravir.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Favipiravir.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Favipiravir.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Favipiravir.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Favipiravir.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Favipiravir.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Favipiravir.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Favipiravir.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Favipiravir.
Silodosin The excretion of Silodosin can be decreased when combined with Favipiravir.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Favipiravir.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Favipiravir.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Favipiravir.
Succinic acid The excretion of Succinic acid can be decreased when combined with Favipiravir.
Citrulline The excretion of Citrulline can be decreased when combined with Favipiravir.
Pravastatin The excretion of Pravastatin can be decreased when combined with Favipiravir.
Oseltamivir The excretion of Oseltamivir can be decreased when combined with Favipiravir.
Cefotiam The excretion of Cefotiam can be decreased when combined with Favipiravir.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Favipiravir.
Tenofovir disoproxil The excretion of Tenofovir disoproxil can be decreased when combined with Favipiravir.
Piperacillin The excretion of Piperacillin can be decreased when combined with Favipiravir.
Indomethacin The excretion of Indomethacin can be decreased when combined with Favipiravir.
Aminohippuric acid The excretion of Aminohippuric acid can be decreased when combined with Favipiravir.
Trifluridine The excretion of Trifluridine can be decreased when combined with Favipiravir.
Allopurinol The excretion of Allopurinol can be decreased when combined with Favipiravir.
Zidovudine The excretion of Zidovudine can be decreased when combined with Favipiravir.
Cimetidine The excretion of Cimetidine can be decreased when combined with Favipiravir.
Cefdinir The excretion of Cefdinir can be decreased when combined with Favipiravir.
Methotrexate The excretion of Methotrexate can be decreased when combined with Favipiravir.
Cephalexin The excretion of Cephalexin can be decreased when combined with Favipiravir.
Valaciclovir The excretion of Valaciclovir can be decreased when combined with Favipiravir.
Levocarnitine The excretion of Levocarnitine can be decreased when combined with Favipiravir.
Leucovorin The excretion of Leucovorin can be decreased when combined with Favipiravir.
Fluorescein The excretion of Fluorescein can be decreased when combined with Favipiravir.
Hydrocortisone The excretion of Hydrocortisone can be decreased when combined with Favipiravir.
Tetracycline The excretion of Tetracycline can be decreased when combined with Favipiravir.
Estradiol The excretion of Estradiol can be decreased when combined with Favipiravir.
Acyclovir The excretion of Acyclovir can be decreased when combined with Favipiravir.
Cefaclor The excretion of Cefaclor can be decreased when combined with Favipiravir.
Ranitidine The excretion of Ranitidine can be decreased when combined with Favipiravir.
Quinapril The excretion of Quinapril can be decreased when combined with Favipiravir.
Bumetanide The excretion of Bumetanide can be decreased when combined with Favipiravir.
Dinoprostone The excretion of Dinoprostone can be decreased when combined with Favipiravir.
Famotidine The excretion of Famotidine can be decreased when combined with Favipiravir.
Fexofenadine The excretion of Fexofenadine can be decreased when combined with Favipiravir.
Hydrochlorothiazide The excretion of Hydrochlorothiazide can be decreased when combined with Favipiravir.
Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Favipiravir.
Rosuvastatin The excretion of Rosuvastatin can be decreased when combined with Favipiravir.
Captopril The excretion of Captopril can be decreased when combined with Favipiravir.
Dexamethasone The excretion of Dexamethasone can be decreased when combined with Favipiravir.
Sitagliptin The excretion of Sitagliptin can be decreased when combined with Favipiravir.
Cefazolin The excretion of Cefazolin can be decreased when combined with Favipiravir.
Ceftizoxime The excretion of Ceftizoxime can be decreased when combined with Favipiravir.
Cefacetrile The excretion of Cefacetrile can be decreased when combined with Favipiravir.
Ceftibuten The excretion of Ceftibuten can be decreased when combined with Favipiravir.
Tazobactam The excretion of Tazobactam can be decreased when combined with Favipiravir.
Cyclic adenosine monophosphate The excretion of Cyclic adenosine monophosphate can be decreased when combined with Favipiravir.
Cholic Acid The excretion of Cholic Acid can be decreased when combined with Favipiravir.
Glutaric Acid The excretion of Glutaric Acid can be decreased when combined with Favipiravir.
Oxalic Acid The excretion of Oxalic Acid can be decreased when combined with Favipiravir.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Favipiravir.
Doripenem The excretion of Doripenem can be decreased when combined with Favipiravir.
Saxagliptin The excretion of Saxagliptin can be decreased when combined with Favipiravir.
Ellagic acid The excretion of Ellagic acid can be decreased when combined with Favipiravir.
Cefaloridine The excretion of Cefaloridine can be decreased when combined with Favipiravir.
Avibactam The excretion of Avibactam can be decreased when combined with Favipiravir.
Eluxadoline The excretion of Eluxadoline can be decreased when combined with Favipiravir.
Silibinin The excretion of Silibinin can be decreased when combined with Favipiravir.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Favipiravir.
Baricitinib The serum concentration of Baricitinib can be increased when it is combined with Favipiravir.
Relebactam The excretion of Relebactam can be decreased when combined with Favipiravir.
Tenofovir The excretion of Tenofovir can be decreased when combined with Favipiravir.
Oxytetracycline The excretion of Oxytetracycline can be decreased when combined with Favipiravir.
Polythiazide The excretion of Polythiazide can be decreased when combined with Favipiravir.
Prednisolone phosphate The excretion of Prednisolone phosphate can be decreased when combined with Favipiravir.
Dexamethasone acetate The excretion of Dexamethasone acetate can be decreased when combined with Favipiravir.
Acamprosate The excretion of Acamprosate can be decreased when combined with Favipiravir.
Vincristine The excretion of Vincristine can be decreased when combined with Favipiravir.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Favipiravir.
Betrixaban The serum concentration of Betrixaban can be increased when it is combined with Favipiravir.
Sildenafil The serum concentration of Sildenafil can be increased when it is combined with Favipiravir.
Morphine The serum concentration of Morphine can be increased when it is combined with Favipiravir.
Clobazam The serum concentration of Clobazam can be increased when it is combined with Favipiravir.
Quinine The serum concentration of Quinine can be increased when it is combined with Favipiravir.
Toremifene The serum concentration of Toremifene can be increased when it is combined with Favipiravir.
Bisoprolol The serum concentration of Bisoprolol can be increased when it is combined with Favipiravir.
Simvastatin The serum concentration of Simvastatin can be increased when it is combined with Favipiravir.
Mannitol The serum concentration of Mannitol can be increased when it is combined with Favipiravir.
Loperamide The excretion of Loperamide can be decreased when combined with Favipiravir.
Vardenafil The serum concentration of Vardenafil can be increased when it is combined with Favipiravir.
Clomifene The serum concentration of Clomifene can be increased when it is combined with Favipiravir.
Tipranavir The serum concentration of Tipranavir can be increased when it is combined with Favipiravir.
Tegaserod The serum concentration of Tegaserod can be increased when it is combined with Favipiravir.
Saquinavir The serum concentration of Saquinavir can be increased when it is combined with Favipiravir.
Posaconazole The serum concentration of Posaconazole can be increased when it is combined with Favipiravir.
Paliperidone The serum concentration of Paliperidone can be increased when it is combined with Favipiravir.
Mibefradil The serum concentration of Mibefradil can be increased when it is combined with Favipiravir.
Belinostat The serum concentration of Belinostat can be increased when it is combined with Favipiravir.
Indacaterol The serum concentration of Indacaterol can be increased when it is combined with Favipiravir.

Target Protein

DNA-directed RNA polymerase subunit beta rpoB
DNA-directed RNA polymerase subunit beta' rpoC
RNA-directed RNA polymerase catalytic subunit PB1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 18328578
    Beigel J, Bray M: Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4.
  • PMID: 18220789
    Hsieh HP, Hsu JT: Strategies of development of antiviral agents directed against influenza virus replication. Curr Pharm Des. 2007;13(34):3531-42.
  • PMID: 17606691
    Gowen BB, Wong MH, Jung KH, Sanders AB, Mendenhall M, Bailey KW, Furuta Y, Sidwell RW: In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob Agents Chemother. 2007 Sep;51(9):3168-76. Epub 2007 Jul 2.
  • PMID: 17194832
    Sidwell RW, Barnard DL, Day CW, Smee DF, Bailey KW, Wong MH, Morrey JD, Furuta Y: Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother. 2007 Mar;51(3):845-51. Epub 2006 Dec 28.
  • PMID: 15728892
    Furuta Y, Takahashi K, Kuno-Maekawa M, Sangawa H, Uehara S, Kozaki K, Nomura N, Egawa H, Shiraki K: Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother. 2005 Mar;49(3):981-6.
  • PMID: 11897578
    Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Nomura N, Egawa H, Minami S, Watanabe Y, Narita H, Shiraki K: In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother. 2002 Apr;46(4):977-81.
  • PMID: 28769016
    Furuta Y, Komeno T, Nakamura T: Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi: 10.2183/pjab.93.027.
  • PMID: 29439438
    Venkataraman S, Prasad BVLS, Selvarajan R: RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Viruses. 2018 Feb 10;10(2). pii: v10020076. doi: 10.3390/v10020076.
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