sofosbuvir/velpatasvir/voxilaprevir

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 CYP2B6, CYP2C8, and CYP3A4. 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 CYP3A4. 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 ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
sofosbuvir (PO)	unknown	2 hr	24 hr
velpatasvir (PO)	unknown	4 hr	24 hr
voxilaprevir (PO)	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of rifampin;
Concurrent use of P-glycoprotein inducers as well as moderate or strong inducers of CYP2B6, CYP2C8, or CYP3A4;
Moderate or severe hepatic impairment (Child-Pugh B or C).

Use Cautiously in:

Receiving immunosuppressant or chemotherapy medications (↑ risk of HBV reactivation);
Severe renal impairment (eGFR <30 mL/min) or end-stage renal disease requiring hemodialysis (no dose recommendation);
OB: Safety not established;
Lactation: Weigh benefits of breast feeding against possible adverse effects;
Geri: May be more sensitive to drug effects;
Pedi: Safety and effectiveness not established.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: fatigue, headache, insomnia

GI: diarrhea, nausea, hepatitis B virus reactivation, hyperbilirubinemia

Interactions ⬆ ⬇

Drug-drug:

Rifampin may ↓ levels/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 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/toxicity of digoxin; therapeutic monitoring of serum digoxin concentrations recommended.
May ↑ levels/risk of bleeding of dabigatran; may need to ↓ dose of dabigatran.
Carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifabutin, and rifapentine may ↓ levels/effectiveness of sofosbuvir, velpatasvir, and voxilaprevir; concurrent use not recommended.
Atazanavir or lopinavir may ↑ levels/toxicity of voxilaprevir; concurrent use not recommended.
Tipranavir/ritonavir may ↓ levels/effectiveness of sofosbuvir and velpatasvir; concurrent use not recommended.
Efavirenz may ↓ levels/effectiveness of velpatasvir and voxilaprevir; concurrent use not recommended.
May ↑ levels/toxicity of tenofovir disoproxil fumarate; monitor closely.
May ↑ levels/toxicity of pravastatin; do not exceed pravastatin dose of 40 mg/day.
May ↑ levels/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/toxicity of voxilaprevir; concurrent use not recommended.
May ↑ levels/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/effectiveness of sofosbuvir, velpatasvir, and voxilaprevir; concurrent use not recommended.

Route/Dosage ⬆ ⬇

PO (Adults ): 1 tablet once daily for 12 wk.

Availability ⬆ ⬇

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

Assessment ⬆ ⬇

Monitor for signs and symptoms of hepatitis B reactivation (jaundice, dark urine, light colored stools, fatigue, weakness, loss of appetite, nausea, vomiting, stomach pain) during therapy.

Lab Test Considerations:

Measure hepatitis B surface antigen (HBsAg) and hepatitis core antibody (anti-HBc) in all patients before starting hepatitis C virus therapy. May cause hepatitis B virus reactivation. Monitor for clinical and laboratory signs of hepatitis flare (↑ AST, ALT, bilirubin, liver failure, death) or HBV reactivation (rapid ↑ in serum HBV DNA level) during HCV treatment and post-treatment follow-up.
- Test patient with HCV genotype 1a infection for presence of virus with NS5A resistance-associated polymorphisms prior to starting therapy with Vosevi™ to determine dose regimen and duration.

Implementation ⬆ ⬇

PO: Administer once daily with food.

Patient/Family Teaching ⬆ ⬇

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 lightheadedness, 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 breast feeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Pot. Nursing Diagnoses ⬆