Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
EPCLUSA 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
EPCLUSA is a fixed-dose combination of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor. Sofosbuvir inhibits HCV RNA replication by acting as a chain terminator, while velpatasvir inhibits HCV replication by binding to NS5A and disrupting viral RNA replication and assembly.
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 (HCV) infection in adults and pediatric patients 3 years and older,Treatment of genotype 1, 2, 3, 4, 5, or 6 HCV infection without cirrhosis or with compensated cirrhosis,Treatment of genotype 1, 2, 3, 4, 5, or 6 HCV infection with decompensated cirrhosis (in combination with ribavirin)
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
400 mg sofosbuvir / 100 mg velpatasvir orally once daily with or without food for 12 weeks.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Sofosbuvir: 0.4 hr (parent), 27 hr (GS-331007); Velpatasvir: 15 hr. Clinical context: once-daily dosing achieves steady-state in ~1 week.
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 in the liver to its active metabolite (GS-461203) via cathepsin A (Cat A) and CES1, followed by phosphorylation. Velpatasvir is metabolized primarily by CYP2B6, CYP2C8, and CYP3A4.
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 (as inactive metabolite GS-331007), 14% fecal; Velpatasvir: 94% fecal, 0.4% renal.
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: 61-65% (human plasma proteins); Velpatasvir: >99.5% (mainly albumin, alpha-1 acid glycoprotein).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Sofosbuvir: ~69 L (calculated as Vd/F); Velpatasvir: ~130 L (calculated as Vd/F). Not typically expressed per kg; indicates extensive tissue distribution.
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Sofosbuvir: ~92% (oral, with food); Velpatasvir: ~25% (fasted), increased with high-fat meal (up to 2-fold).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
No dose adjustment required for GFR ≥30 m L/min. Safety and efficacy not established for GFR <30 m L/min or hemodialysis; use with caution and consider alternative therapy.
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.
No dose adjustment for mild or moderate hepatic impairment (Child-Pugh A or B). Not recommended for use in severe hepatic impairment (Child-Pugh C) due to higher exposures of velpatasvir.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
For patients ≥6 years old or weighing ≥17 kg: fixed-dose combination (400 mg/100 mg) once daily with or without food, regardless of weight, for 12 weeks. Safety and efficacy not established for children <6 years or weighing <17 kg.
Not recommended for children under 18 years due to risk of respiratory depression.
No specific dose adjustment required based on age; use same dosing as younger adults, with monitoring for comorbidities and potential drug interactions.
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 (HBV) reactivation in patients coinfected with HCV and HBV. Test all patients for evidence of current or prior HBV infection before initiating treatment. Monitor for HBV reactivation during and after treatment.
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 in patients coinfected with HCV and HBV,Increased risk of bradycardia when used with amiodarone, especially in patients on beta-blockers or with cardiac comorbidities,Possible decreased therapeutic effect with strong P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort),Not recommended in patients with severe renal impairment (e GFR <30 m L/min) or end-stage renal disease requiring dialysis
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 amiodarone (risk of symptomatic bradycardia),Concomitant use with strong P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort)
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.
Take with or without food. No specific dietary restrictions. Avoid grapefruit juice? No interaction reported. Avoid alcohol as it can worsen liver disease.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
EPCLUSA (sofosbuvir/velpatasvir) is contraindicated in pregnancy due to the teratogenic risk associated with ribavirin (if used in combination). In the absence of ribavirin, there are no adequate human data; animal studies show no evidence of teratogenicity at clinically relevant exposures. However, due to the potential for ribavirin co-administration in some HCV regimens, pregnancy must be excluded before initiation and avoided during treatment and for 6 months after in females of childbearing potential.
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 the presence of sofosbuvir or velpatasvir in human milk, effects on the breastfed infant, or milk production. Because of the potential for adverse effects in the breastfed infant, breastfeeding is not recommended during treatment and for 6 months after the last dose, especially if ribavirin is co-administered. M/P ratio: unknown.
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 dose adjustment is recommended for EPCLUSA based on pregnancy alone. However, pharmacokinetic changes in pregnancy may alter drug exposure; therapeutic drug monitoring is not currently recommended. Safety and efficacy in pregnant women have not been established.
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.
EPCLUSA (sofosbuvir/velpatasvir) is a pangenotypic NS5B polymerase inhibitor and NS5A inhibitor combination for chronic HCV. For decompensated cirrhosis (Child-Pugh B/C), co-administer with ribavirin. Monitor for bradycardia when used with amiodarone; avoid co-administration if possible. Check for polymorphisms at baseline if HCV genotype 3 and cirrhosis (consider extending treatment). Assess renal function; not recommended if e GFR <30 m L/min/1.73m² unless on dialysis and benefit outweighs risk.
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 one tablet (400 mg sofosbuvir/100 mg velpatasvir) orally once daily with or without food.,Complete the full course of treatment (12 weeks for most patients; 24 weeks for genotype 3 with cirrhosis or prior treatment failure).,Use of amiodarone with EPCLUSA can cause serious slowing of heartbeat (bradycardia). Inform your doctor if you take amiodarone.,Avoid taking rifampin, St. John's wort, or certain anticonvulsants (carbamazepine, phenytoin) as they reduce EPCLUSA effectiveness.,Report any symptoms of hepatitis B reactivation (fatigue, jaundice, dark urine) immediately.,If you have diabetes, monitor blood glucose closely as treatment may improve glucose control.,Use effective contraception during treatment and for 6 months after if using combined oral contraceptives containing ethinyl estradiol.
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 EPCLUSA vs ANEXSIA 5/325, answered by our medical review team.
EPCLUSA is a Direct-Acting Antiviral (DAA) for Hepatitis C that works by EPCLUSA is a fixed-dose combination of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor. Sofosbuvir inhibits HCV RNA replication by acting as a chain terminator, while velpatasvir inhibits HCV replication by binding to NS5A and disrupting viral RNA replication and assembly.. 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 EPCLUSA 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 EPCLUSA is: 400 mg sofosbuvir / 100 mg velpatasvir orally once daily with or without food for 12 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 EPCLUSA 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. EPCLUSA is classified as Category C. EPCLUSA (sofosbuvir/velpatasvir) is contraindicated in pregnancy due to the teratogenic risk associated with ribavirin (if used in combination). In the absence of ribavirin, there . 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.