Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
VOSEVI vs ANEXSIA 5/325
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) is a fixed-dose combination of a nucleotide analog NS5B polymerase inhibitor (sofosbuvir), an NS5A inhibitor (velpatasvir), and a NS3/4A protease inhibitor (voxilaprevir). The combination inhibits hepatitis C virus replication by targeting multiple viral proteins.
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
Treatment of chronic hepatitis C virus genotype 1-6 infection in adults who have no prior treatment with a NS5A inhibitor and have been previously treated with a regimen containing sofosbuvir without a NS5A inhibitor,Treatment of chronic hepatitis C virus genotype 1-6 infection in adults who have prior treatment with a NS5A inhibitor-containing regimen
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
One tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) orally once daily with food for 8 weeks.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Sofosbuvir: 0.5 h (parent), 27 h (GS-331007 metabolite); Velpatasvir: 17 h; Voxilaprevir: 33 h. Terminal half-lives support once-daily dosing; metabolite GS-331007 accumulates but is less active.
Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose.
Sofosbuvir is metabolized by cathepsin A and CES1 to the active metabolite GS-461203, followed by dephosphorylation. Velpatasvir and voxilaprevir are metabolized by CYP2B6, CYP2C8, CYP3A4 (minor). Voxilaprevir is also a substrate of OATP1B1/1B3.
Hydrocodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI.
Sofosbuvir: 80% renal, 14% fecal; Velpatasvir: 94% fecal, 0.4% renal; Voxilaprevir: 40% renal, 47% fecal. VOSEVI components are eliminated primarily via biliary/fecal (velpatasvir, voxilaprevir) and renal (sofosbuvir) pathways.
Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged.
Sofosbuvir: ~85% bound; Velpatasvir: >99.5% bound; Voxilaprevir: >99% bound. Primarily to albumin.
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Sofosbuvir: ~1.8 L/kg; Velpatasvir: ~4.9 L/kg; Voxilaprevir: ~3.9 L/kg. Large Vd indicates extensive tissue distribution, including liver (target organ).
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Oral: sofosbuvir ~92%, velpatasvir ~29%, voxilaprevir ~44% (fasted). Administer with food to increase absorption (especially voxilaprevir AUC 2- to 4-fold).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
No dose adjustment required for mild to moderate renal impairment (e GFR ≥30 m L/min/1.73 m²). For severe renal impairment (e GFR <30 m L/min/1.73 m²) or end-stage renal disease, safety and efficacy not established; use not recommended.
GFR 30-50 m L/min: use with caution, increase dosing interval to every 6 hours; GFR <30 m L/min: avoid use due to hydrocodeone accumulation.
Contraindicated in Child-Pugh class B or C decompensated cirrhosis due to increased voxilaprevir exposure. No dose adjustment required for Child-Pugh class A cirrhosis.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
Safety and efficacy in pediatric patients <18 years have not been established; no specific dosing recommendations.
Not recommended for children under 18 years due to risk of respiratory depression.
No dose adjustment required based on age. Clinical studies included patients ≥65 years with no overall differences in safety or efficacy; consider renal function monitoring.
Start with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk.
Risk of hepatitis B virus reactivation in patients coinfected with HCV and HBV. Test all patients for evidence of current or prior HBV infection before starting treatment. Monitor HCV/HBV coinfected patients for hepatitis B reactivation during treatment and post-treatment follow-up.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
Risk of HBV reactivation,Risk of bradycardia when coadministered with amiodarone; avoid use unless alternatives are not available,Decompensated hepatic impairment: not recommended for use in patients with moderate or severe hepatic impairment (Child-Pugh B or C),Drug interactions: potential for reduced therapeutic effect if given with P-gp inducers (e.g., rifampin) or moderate/strong CYP inducers
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome.
Concomitant use with rifampin (CYP2B6 and P-gp inducer) due to significant decrease in voxilaprevir concentrations,Concomitant use with St. John's wort (Hypericum perforatum) due to decreased drug concentrations,Coadministration with rosuvastatin is contraindicated due to increased risk of myopathy/rhabdomyolysis,Severe hepatic impairment (Child-Pugh C)
Hypersensitivity to hydrocodone or acetaminophen; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; known or suspected paralytic ileus; severe hepatic impairment; and concurrent use of MAOIs within 14 days.
VOSEVI should be taken with food to ensure adequate absorption. A high-fat meal (approximately 800–1000 calories, 50% fat) increases absorption of velpatasvir and voxilaprevir. Avoid concurrent use with St. John's wort, rifampin, and other P-glycoprotein inducers, as they may reduce VOSEVI efficacy.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
VOSEVI is contraindicated in pregnancy due to risk of fetal harm. No adequate human data; animal studies show developmental toxicity at clinically relevant exposures. Use effective contraception during treatment and for 6 months after completion.
First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed.
No data on presence in human milk; animal studies indicate excretion. M/P ratio unknown. Risk of adverse effects in infant not excluded; advise against breastfeeding during therapy.
Paracetamol and hydrocodone are excreted in breast milk. M/P ratio: paracetamol ~1.0, hydrocodone ~1.0-2.0. Use with caution; monitor infant for drowsiness and respiratory depression. Consider risk of infant sedation with long-term use.
No data on pharmacokinetic changes in pregnancy; dose adjustments not established. VOSEVI is not recommended in pregnancy; if inadvertent exposure occurs, consult specialist.
Increased clearance in pregnancy may require dose adjustment. Monitor for pain control and adverse effects; no fixed dose change recommended. Consider lower starting dose due to potential fetal risks. Avoid chronic use; taper if possible.
VOSEVI is a fixed-dose combination of sofosbuvir (NS5B inhibitor), velpatasvir (NS5A inhibitor), and voxilaprevir (NS3/4A protease inhibitor) indicated for treatment-naive and treatment-experienced patients with chronic HCV genotype 1–6 without cirrhosis or with compensated cirrhosis. It is particularly useful for patients who have failed prior NS5A inhibitor-containing regimens, including those with genotype 3 and compensated cirrhosis. Monitor for hepatitis B reactivation in HBV co-infected patients. Dose adjustment not required for mild or moderate renal impairment, but safety not established in severe renal impairment or ESRD. Caution with amiodarone due to risk of serious bradycardia. Check for drug interactions with P-gp inducers, CYP2B6, CYP2C8, and CYP3A4 substrates.
ANEXSIA 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days.
Take VOSEVI exactly as prescribed, usually one tablet once daily with food.,Do not skip doses or stop taking VOSEVI without talking to your doctor.,If you have hepatitis B co-infection, your doctor will monitor you for HBV reactivation during and after treatment.,Tell your doctor about all medications, including over-the-counter drugs, herbal supplements, and vitamins, as VOSEVI may interact with them.,Common side effects include headache, fatigue, diarrhea, and nausea. Contact your doctor if you experience severe abdominal pain, jaundice, or signs of liver injury.,VOSEVI does not prevent transmission of HCV. Practice safe sex and avoid sharing needles to reduce the risk of spreading the virus.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication.,Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you.,Store securely out of reach of others; dispose of unused medication via drug take-back programs.,Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about VOSEVI vs ANEXSIA 5/325, answered by our medical review team.
VOSEVI is a Direct-Acting Antiviral Combination that works by VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) is a fixed-dose combination of a nucleotide analog NS5B polymerase inhibitor (sofosbuvir), an NS5A inhibitor (velpatasvir), and a NS3/4A protease inhibitor (voxilaprevir). The combination inhibits hepatitis C virus replication by targeting multiple viral proteins.. ANEXSIA 5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between VOSEVI and ANEXSIA 5/325 depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of VOSEVI is: One tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) orally once daily with food for 8 weeks.. The standard adult dose of ANEXSIA 5/325 is: 1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between VOSEVI and ANEXSIA 5/325 in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. VOSEVI is classified as Category C. VOSEVI is contraindicated in pregnancy due to risk of fetal harm. No adequate human data; animal studies show developmental toxicity at clinically relevant exposures. Use effective. ANEXSIA 5/325 is classified as Category C. First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal re. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.