Indications
Sofosbuvir + Velpatasvir is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor. It is indicated for the treatment of adults and children aged 3 years and older with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection. This applies to people without cirrhosis or with compensated cirrhosis. For people with decompensated cirrhosis, it is used in combination with ribavirin.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Mechanism of action
Sofosbuvir blocks the HCV NS5B RNA-dependent RNA polymerase, an enzyme the virus needs to replicate. It is a nucleotide prodrug, so it is first broken down inside the cell into the active uridine analog triphosphate (GS-461203). The NS5B polymerase can build GS-461203 into HCV RNA, and once it is in, it acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a, with IC50 values from 0.36 to 3.3 micromolar. It does not inhibit human DNA polymerases or human RNA polymerases, and it does not inhibit mitochondrial RNA polymerase.
Velpatasvir blocks the HCV NS5A protein, which the virus also needs to replicate. Resistance selection in cell culture and cross-resistance studies point to NS5A as the target of velpatasvir.
Pharmacodynamics
Cardiac electrophysiology
A thorough QT trial with an active control (Moxifloxacin 400 mg) looked at the effect of Sofosbuvir on the QTc interval, at 400 mg (the recommended dosage) and at 1200 mg (three times the recommended dosage). At three times the recommended dose, Sofosbuvir does not prolong QTc to any clinically relevant extent. A second thorough QT trial, also with Moxifloxacin 400 mg as the active control, tested Velpatasvir 500 mg, which is five times the recommended dosage. At that dose, Velpatasvir does not prolong the QTc interval to any clinically relevant extent either.
Pregnancy & Breastfeeding
Pregnancy: If Sofosbuvir + Velpatasvir is given with Ribavirin, the combination must not be used in pregnant women or in men whose female partners are pregnant. For the risks Ribavirin carries in pregnancy, please read the Ribavirin prescribing information.
Lactation: No one knows yet whether the components of Velpatasvir and Sofosbuvir, or their metabolites, pass into human breast milk. It is also not known whether they affect milk production or have any effect on a breastfed infant.
Females and males of reproductive potential: If Sofosbuvir and Velpatasvir is given with Ribavirin, what the Ribavirin information says about pregnancy testing, contraception and infertility applies to the combination as well. The Ribavirin prescribing information has more detail.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.
Side Effects & Interactions
Side Effects
No side-effect data recorded yet.