• Chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have previously been treated with an HCV regimen containing an NS5A inhibitor.
• Chronic HCV genotype 1a or 3 infection in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

Contraindicated in:

• Concurrent use of rifampin
• Moderate or severe hepatic impairment.

Use Cautiously in:

• Concurrent use of immunosuppressant or chemotherapy medications (↑ risk of hepatitis B virus [HBV] reactivation)
• OB: Safety not established in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be more sensitive to drug effects.

GI: diarrhea, nausea, HBV reactivation, hyperbilirubinemia.

Neuro: fatigue, headache, insomnia.

Drug-Drug:

• Rifampin may ↓ levels and effectiveness of sofosbuvir, velpatasvir, and voxilaprevir; concurrent use contraindicated.
• Amiodarone may ↑ risk of symptomatic bradycardia when used with sofosbuvir-containing regimens; concurrent use not recommended; if amiodarone necessary, monitor patients in inpatient setting for first 48 hr of concomitant use and then monitor heart rate on outpatient basis for at least the first 2 wk of treatment; follow same monitoring procedure if discontinuing amiodarone immediately before initiation of sofosbuvir/velpatasvir/voxilaprevir.
• Acid-reducing agents may ↓ levels and effectiveness of velpatasvir; separate administration from antacids, including magnesium hydroxide and aluminum hydroxide, by 4 hr; administer H₂-receptor antagonists simultaneously or 12 hr apart from sofosbuvir/velpatasvir/voxilaprevir (dose of H₂ antagonist should not exceed famotidine 40 mg twice daily or equivalent); may use with omeprazole 20 mg (use with other proton-pump inhibitors not studied).
• May ↑ levels and risk of toxicity of digoxin; therapeutic monitoring of serum digoxin concentrations recommended.
• May ↑ levels and risk of bleeding of dabigatran; may need to ↓ dose of dabigatran.
• Carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifabutin, and rifapentine may ↓ levels and effectiveness of sofosbuvir, velpatasvir, and voxilaprevir; concurrent use not recommended.
• Atazanavir or lopinavir may ↑ levels and risk of toxicity of voxilaprevir; concurrent use not recommended.
• Tipranavir/ritonavir may ↓ levels and effectiveness of sofosbuvir and velpatasvir; concurrent use not recommended.
• Efavirenz may ↓ levels and effectiveness of velpatasvir and voxilaprevir; concurrent use not recommended.
• May ↑ levels and risk of toxicity of tenofovir disoproxil fumarate; monitor closely.
• May ↑ levels and risk of toxicity of pravastatin; do not exceed pravastatin dose of 40 mg/day.
• May ↑ levels and risk of toxicity of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin; do not exceed pravastatin dose of 40 mg/day; concurrent use with pitavastatin or rosuvastatin not recommended; use the lowest possible dose of atorvastatin, fluvastatin, lovastatin, and simvastatin.
• Cyclosporine may ↑ levels and risk of toxicity of voxilaprevir; concurrent use not recommended.
• May ↑ levels and risk of toxicity of imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, sulfasalazine, or topotecan; concurrent use not recommended.
• May cause fluctuations in INR when used with warfarin; closely monitor INR.
• May ↑ risk of hypoglycemia when used with certain antidiabetic agents.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness of sofosbuvir, velpatasvir, and voxilaprevir; concurrent use not recommended.

• Tablets: sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg;

• PO (Adults): One tablet once daily for 12 wk.

Vosevi

• 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.

• Decreased levels of HCV with sustained virologic response and lessened sequelae of chronic HCV infection.

Therapeutic Classification: antivirals

Pharmacologic Classification: NS5A inhibitors, protease inhibitors

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.

(plasma concentrations)

• Instruct patient to take medication as directed. Do not skip or miss doses. Do not stop medication without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional if signs and symptoms of bradycardia (near-fainting or fainting, dizziness or light-headedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion, memory problems) occur.
• Advise patient to notify health care professional if they have a history of HBV. May cause reactivation.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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