Peringatan Keamanan

No indication of carcinogenicity or impairment of fertility/fetal viability FDA Label.

Velpatasvir

DB11613

small molecule approved investigational

Deskripsi

Velpatasvir is a Direct-Acting Antiviral (DAA) medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). 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. Velpatasvir acts as a defective substrate for NS5A (Non-Structural Protein 5A), a non-enzymatic viral protein that plays a key role in Hepatitis C Virus replication, assembly, and modulation of host immune responses A19175. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as velpatasvir. Notably, velpatasvir has a significantly higher barrier to resistance than the first generation NS5A inhibitors, such as DB09027 and DB09102, making it a highly potent and reliable alternative for treatment of chronic Hepatitis C A19637.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Velpatasvir as first line therapy in combination with sofosbuvir for all six genotypes of Hepatitis C L852. Velpatasvir is currently only available within a fixed dose combination product as Epclusa with DB08934, another direct acting antiviral. Goals of therapy for Epclusa include the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality and risk of requiring a liver transplant A19626.

Since June 2016, Velpatasvir has been available as a fixed dose combination product with DB08934, as the commercially available product Epclusa. Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. It is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis and a high barrier to resistance L852. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV L852, A19626.

Struktur Molekul 2D

Berat 883.019
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) 15h [FDA Label].
Volume Distribusi 1.4-1.6 L/kg [A19175].
Klirens (Clearance) Estimated 0.12 L/h/kg [A19175.

Absorpsi

Oral bioavailability of 25-30% A19175.

Metabolisme

Some metabolism by CYP2B6, CYP2C8, and CYP3A4 A19175.

Rute Eliminasi

94% excreted in feces with 77% as parent compound. 0.4% excreted in urine FDA Label.

Interaksi Makanan

2 Data
  • 1. Avoid St. John's Wort.
  • 2. Take with or without food. Multiple different combination products contain velpatasvir. Take Epclusa with or without food. Take Vosevi with food.

Interaksi Obat

628 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Velpatasvir.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Velpatasvir.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Velpatasvir.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Velpatasvir.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Velpatasvir.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Velpatasvir.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Velpatasvir.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Velpatasvir.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Velpatasvir.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Velpatasvir.
Silodosin The excretion of Silodosin can be decreased when combined with Velpatasvir.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Velpatasvir.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Velpatasvir.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Velpatasvir.
Mifepristone The serum concentration of Velpatasvir can be increased when it is combined with Mifepristone.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Velpatasvir.
Vincristine The excretion of Vincristine can be decreased when combined with Velpatasvir.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Velpatasvir.
Lumacaftor The serum concentration of Velpatasvir can be decreased when it is combined with Lumacaftor.
Secobarbital The metabolism of Velpatasvir can be increased when combined with Secobarbital.
Rifampin The metabolism of Velpatasvir can be increased when combined with Rifampicin.
Phenobarbital The metabolism of Velpatasvir can be increased when combined with Phenobarbital.
Bexarotene The metabolism of Velpatasvir can be decreased when combined with Bexarotene.
Diltiazem The metabolism of Velpatasvir can be decreased when combined with Diltiazem.
Medroxyprogesterone acetate The metabolism of Velpatasvir can be decreased when combined with Medroxyprogesterone acetate.
Nicardipine The metabolism of Velpatasvir can be decreased when combined with Nicardipine.
Irbesartan The metabolism of Velpatasvir can be decreased when combined with Irbesartan.
Oxybutynin The metabolism of Velpatasvir can be decreased when combined with Oxybutynin.
Fluvastatin The metabolism of Velpatasvir can be decreased when combined with Fluvastatin.
Pioglitazone The metabolism of Velpatasvir can be decreased when combined with Pioglitazone.
Abiraterone The metabolism of Velpatasvir can be decreased when combined with Abiraterone.
Levothyroxine The metabolism of Velpatasvir can be decreased when combined with Levothyroxine.
Loratadine The metabolism of Velpatasvir can be decreased when combined with Loratadine.
Trimethoprim The metabolism of Velpatasvir can be decreased when combined with Trimethoprim.
Fluticasone propionate The metabolism of Velpatasvir can be decreased when combined with Fluticasone propionate.
Clopidogrel The metabolism of Velpatasvir can be decreased when combined with Clopidogrel.
Candesartan cilexetil The metabolism of Velpatasvir can be decreased when combined with Candesartan cilexetil.
Salmeterol The metabolism of Velpatasvir can be decreased when combined with Salmeterol.
Gemfibrozil The metabolism of Velpatasvir can be decreased when combined with Gemfibrozil.
Fluticasone The metabolism of Velpatasvir can be decreased when combined with Fluticasone.
Mometasone furoate The metabolism of Velpatasvir can be decreased when combined with Mometasone furoate.
Felodipine The metabolism of Velpatasvir can be decreased when combined with Felodipine.
Betrixaban The serum concentration of Betrixaban can be increased when it is combined with Velpatasvir.
Vemurafenib The serum concentration of Velpatasvir can be increased when it is combined with Vemurafenib.
Apalutamide The serum concentration of Velpatasvir can be decreased when it is combined with Apalutamide.
Pitolisant The serum concentration of Velpatasvir can be decreased when it is combined with Pitolisant.
Isavuconazole The serum concentration of Velpatasvir can be increased when it is combined with Isavuconazole.
Isavuconazonium The serum concentration of Velpatasvir can be increased when it is combined with Isavuconazonium.
Imatinib Imatinib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Novobiocin Novobiocin may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Hesperetin Hesperetin may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Rabeprazole Rabeprazole may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Genistein The metabolism of Velpatasvir can be decreased when combined with Genistein.
Topiroxostat The metabolism of Velpatasvir can be decreased when combined with Topiroxostat.
Daidzin Daidzin may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Fusidic acid The metabolism of Velpatasvir can be decreased when combined with Fusidic acid.
Naringenin Naringenin may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Vandetanib Vandetanib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Eltrombopag The metabolism of Velpatasvir can be decreased when combined with Eltrombopag.
Simeprevir The metabolism of Velpatasvir can be decreased when combined with Simeprevir.
Safinamide Safinamide may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Teriflunomide The metabolism of Velpatasvir can be decreased when combined with Teriflunomide.
Cannabidiol Cannabidiol may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Palbociclib Palbociclib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Folic acid Velpatasvir may decrease the excretion rate of Folic acid which could result in a higher serum level.
Allopurinol Velpatasvir may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Celecoxib Velpatasvir may decrease the excretion rate of Celecoxib which could result in a higher serum level.
Oxaliplatin Velpatasvir may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Methotrexate Velpatasvir may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Clofarabine Velpatasvir may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Nitrofurantoin Velpatasvir may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Riluzole Velpatasvir may decrease the excretion rate of Riluzole which could result in a higher serum level.
Tegaserod Velpatasvir may decrease the excretion rate of Tegaserod which could result in a higher serum level.
Leflunomide Velpatasvir may decrease the excretion rate of Leflunomide which could result in a higher serum level.
Rosuvastatin Velpatasvir may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Alvocidib Velpatasvir may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Riociguat Velpatasvir may decrease the excretion rate of Riociguat which could result in a higher serum level.
Lenvatinib Velpatasvir may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
Fimasartan Velpatasvir may decrease the excretion rate of Fimasartan which could result in a higher serum level.
Delafloxacin Velpatasvir may decrease the excretion rate of Delafloxacin which could result in a higher serum level.
Glasdegib Velpatasvir may decrease the excretion rate of Glasdegib which could result in a higher serum level.
Fostamatinib Fostamatinib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Gilteritinib Gilteritinib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Nabiximols Nabiximols may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Fedratinib The serum concentration of Velpatasvir can be increased when it is combined with Fedratinib.
Caffeine Caffeine may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Dronabinol The metabolism of Velpatasvir can be decreased when combined with Dronabinol.
Tazemetostat Velpatasvir may decrease the excretion rate of Tazemetostat which could result in a higher serum level.
Pantoprazole Pantoprazole may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Diethylstilbestrol Diethylstilbestrol may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Gefitinib Gefitinib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Beclomethasone dipropionate Beclomethasone dipropionate may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Progesterone Progesterone may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Lansoprazole Lansoprazole may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Estradiol Estradiol may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Buprenorphine Buprenorphine may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Telmisartan Telmisartan may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Sunitinib Sunitinib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Quercetin Quercetin may decrease the excretion rate of Velpatasvir which could result in a higher serum level.

Target Protein

Nonstructural protein 5A NS5A

Referensi & Sumber

Artikel (PubMed)
  • PMID: 24755925
    Ascher DB, Wielens J, Nero TL, Doughty L, Morton CJ, Parker MW: Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA. Sci Rep. 2014 Apr 23;4:4765. doi: 10.1038/srep04765.
  • PMID: 21507963
    Targett-Adams P, Graham EJ, Middleton J, Palmer A, Shaw SM, Lavender H, Brain P, Tran TD, Jones LH, Wakenhut F, Stammen B, Pryde D, Pickford C, Westby M: Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action. J Virol. 2011 Jul;85(13):6353-68. doi: 10.1128/JVI.00215-11. Epub 2011 Apr 20.
  • PMID: 28193657
    Mogalian E, German P, Kearney BP, Yang CY, Brainard D, Link J, McNally J, Han L, Ling J, Mathias A: Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02084-16. doi: 10.1128/AAC.02084-16. Print 2017 May.
  • PMID: 26183611
    Lawitz E, Freilich B, Link J, German P, Mo H, Han L, Brainard DM, McNally J, Marbury T, Rodriguez-Torres M: A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus. J Viral Hepat. 2015 Dec;22(12):1011-9. doi: 10.1111/jvh.12435. Epub 2015 Jul 16.
  • 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: 27353271
    Lawitz EJ, Dvory-Sobol H, Doehle BP, Worth AS, McNally J, Brainard DM, Link JO, Miller MD, Mo H: Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5368-78. doi: 10.1128/AAC.00763-16. Print 2016 Sep.

Contoh Produk & Brand

Produk: 15 • International brands: 0
Produk
  • Epclusa
    Tablet, film coated • - • Oral • US • Approved
  • Epclusa
    Tablet, film coated • - • Oral • US • Approved
  • Epclusa
    Pellet • - • Oral • US • Approved
  • Epclusa
    Pellet • - • Oral • US • Approved
  • Epclusa
    Tablet • - • Oral • Canada • Approved
  • Epclusa
    Tablet, film coated • - • Oral • EU • Approved
  • Epclusa
    Tablet, film coated • - • Oral • EU • Approved
  • Epclusa
    Pellet • - • Oral • EU • Approved
Menampilkan 8 dari 15 produk.

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