Sofosbuvir/velpatasvir/voxilaprevir

Sofosbuvir/velpatasvir/voxilaprevir
Combination of
SofosbuvirNS5B RNA polymerase inhibitor
VelpatasvirNS5A inhibitor
VoxilaprevirNS3/4A protease inhibitor
Clinical data
Trade namesVosevi
AHFS/Drugs.comMonograph
MedlinePlusa617037
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
Identifiers
PubChem CID
KEGG
Chemical and physical data
FormulaC111H135F5N17O26PS
Molar mass2281.42 g·mol−1
3D model (JSmol)
  • CCC1C2CN(C1C(=O)NC3(CC3C(F)F)C(=O)NS(=O)(=O)C4(CC4)C)C(=O)C(NC(=O)OC5CC5CCCCC(C6=NC7=C(C=C(C=C7)OC)N=C6O2)(F)F)C(C)(C)C.CC1CCC(N1C(=O)C(C(C)C)NC(=O)OC)C2=NC3=C(N2)C=CC4=CC5=C(C=C43)OCC6=C5C=CC(=C6)C7=CN=C(N7)C8CC(CN8C(=O)C(C9=CC=CC=C9)NC(=O)OC)COC.CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
  • InChI=1S/C49H54N8O8.C40H52F4N6O9S.C22H29FN3O9P/c1-26(2)41(54-48(60)63-5)47(59)57-27(3)12-17-38(57)45-51-36-16-14-30-20-35-33-15-13-31(19-32(33)25-65-40(35)21-34(30)43(36)53-45)37-22-50-44(52-37)39-18-28(24-62-4)23-56(39)46(58)42(55-49(61)64-6)29-10-8-7-9-11-29;1-7-22-27-19-50(28(22)32(51)48-39(18-23(39)31(41)42)35(53)49-60(55,56)38(5)14-15-38)34(52)30(37(2,3)4)47-36(54)59-26-16-20(26)10-8-9-13-40(43,44)29-33(58-27)46-25-17-21(57-6)11-12-24(25)45-29;1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h7-11,13-16,19-22,26-28,38-39,41-42H,12,17-18,23-25H2,1-6H3,(H,50,52)(H,51,53)(H,54,60)(H,55,61);11-12,17,20,22-23,26-28,30-31H,7-10,13-16,18-19H2,1-6H3,(H,47,54)(H,48,51)(H,49,53);5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t27-,28-,38-,39-,41-,42+;20-,22-,23+,26-,27+,28+,30-,39-;14-,16+,18+,20+,22+,36-/m010/s1
  • Key:FMWRYUBVSONSCK-ZYTFCPLVSA-N

Sofosbuvir/velpatasvir/voxilaprevir, sold under the brand name Vosevi, is a fixed-dose combination medication for the treatment of hepatitis C. It contains sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor; velpatasvir, an HCV NS5A inhibitor; and voxilaprevir an HCV NS3/4A protease inhibitor.[2][5]

The most common adverse reactions include headache, fatigue, diarrhea, and nausea.[6]

The combination was approved for medical use in the United States and in the European Union in July 2017.[6][3] Vosevi is sold by Gilead Sciences.[6]

Medical uses

In the US, sofosbuvir/velpatasvir/voxilaprevir is indicated for the treatment of adults with chronic hepatitis C virus infection without cirrhosis (liver disease) or with compensated cirrhosis (Child-Pugh A).[2][6]

In the EU, it is indicated for the treatment of chronic hepatitis C virus infection in people aged twelve years of aged and older and weighing at least 30 kilograms (66 lb).[3][4]

Adverse effects

The FDA label for sofosbuvir/velpatasvir/voxilaprevir contains a boxed warning about the risk of Hepatitis B virus reactivation.[2]

History

The safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir was evaluated in two phase III clinical trials that enrolled approximately 750 adults without cirrhosis or with mild cirrhosis.[6] The first trial compared twelve weeks of treatment with the combination versus treatment with placebo in adults with genotype 1 who had previously failed treatment with an NS5A inhibitor drug.[6] Participants with genotypes 2, 3, 4, 5, or 6 all received the combination.[6] The second trial compared twelve weeks of treatment with the combination versus treatment with the previously approved drugs sofosbuvir and velpatasvir in adults with genotypes 1, 2, or 3 who had previously failed treatment with sofosbuvir but not an NS5A inhibitor drug.[6] Results of both trials demonstrated that 96-97 percent of participants who received the combination had no virus detected in the blood 12 weeks after finishing treatment, suggesting that participants’ infection had been cured.[6]

The US Food and Drug Administration (FDA) granted the application for sofosbuvir/velpatasvir/voxilaprevir priority review and breakthrough therapy designations.[6] The FDA granted approval of Vosevi to Gilead Sciences Inc.[6]

References

  1. ^ "Liver disease". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  2. ^ a b c d "Vosevi- sofosbuvir, velpatasvir, and voxilaprevir tablet, film coated". DailyMed. 14 March 2024. Retrieved 29 June 2024.
  3. ^ a b c "Vosevi EPAR". European Medicines Agency (EMA). 22 September 2017. Retrieved 24 September 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ^ a b "Vosevi PI". Union Register of medicinal products. 28 July 2017. Retrieved 29 June 2024.
  5. ^ Childs-Kean LM, Brumwell NA, Lodl EF (2019). "Profile of sofosbuvir/velpatasvir/voxilaprevir in the treatment of hepatitis C". Infection and Drug Resistance. 12: 2259–2268. doi:10.2147/IDR.S171338. PMC 6662169. PMID 31413603.
  6. ^ a b c d e f g h i j k "FDA approves Vosevi for Hepatitis C". U.S. Food and Drug Administration (FDA) (Press release). 18 July 2017. Archived from the original on 23 July 2017. Retrieved 27 July 2017. Public Domain This article incorporates text from this source, which is in the public domain.