section name header

Pronunciation

soe-FOS-bue-vir/vel-PAT-as-vir/vox-i-LA-pre-vir

Classifications

Therapeutic Classification: antivirals

Pharmacologic Classification: ns5b inhibitors, NS5A inhibitors, protease inhibitors

Indications

REMS


Action

  • Sofosbuvir: inhibits the HCV NS5B RNA-dependent RNA polymerase, resulting in inhibition of viral replication. Velpatasvir: inhibits the HCV NS5A protein, resulting in inhibition of viral replication. Voxilaprevir: inhibitor of NS3/4A protease, an enzyme necessary for viral replication.
Therapeutic effects:
  • Decreased levels of HCV with sustained virologic response and lessened sequelae of chronic HCV infection.

Pharmacokinetics

Sofosbuvir

Absorption: Prodrug that is rapidly metabolized to its active form (GS-461203) following absorption.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized primarily to GS-461203, an active antiviral moiety, then converted to GS-331007, which does not have antiviral activity. 80% excreted in urine mostly as GS-331007, 14% excreted in feces.

Half-Life: Sofosbuvir: 0.5 hr; GS-331007: 29 hr.

Velpatasvir

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized in the liver primarily via the CYP2B6, CYP2C8, and CYP3A4 isoenzymes. Primarily undergoes biliary excretion, with 94% excreted in feces (77% as unchanged drug) and 0.4% eliminated in urine.

Half-Life: 17 hr.

Voxilaprevir

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized in the liver primarily via the CYP3A4 isoenzyme. Primarily undergoes biliary excretion, with 94% excreted in feces (40% as unchanged drug) and 0% eliminated in urine.

Half-Life: 33 hr.

Time/Action Profile

(plasma concentrations)

ROUTEONSETPEAKDURATION
sofosbuvir (PO)unknown2 hr24 hr
velpatasvir (PO)unknown4 hr24 hr
voxilaprevir (PO)unknown4 hr24 hr





Contraind./Precautions

Contraindicated in:

Use Cautiously in:

Adv. Reactions/Side Effects

GI: diarrhea, nausea, HBV reactivation, hyperbilirubinemia

Neuro: fatigue, headache, insomnia

Interactions

Drug-drug:

Drug-Natural Products:

Route/Dosage

Availability

Assessment

Lab Test Considerations:

Implementation

Patient/Family Teaching

Evaluation/Desired Outcomes

US Brand Names

Vosevi