Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ZEPATIER vs CO-GESIC
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
ZEPATIER is a fixed-dose combination of elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. Elbasvir inhibits HCV NS5A, disrupting viral replication and assembly. Grazoprevir inhibits the HCV NS3/4A serine protease, preventing cleavage of the HCV polyprotein into mature viral proteins.
CO-GESIC (hydrocodone/acetaminophen) is a combination analgesic. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing prostaglandin synthesis and elevating pain threshold.
Treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults,Treatment of chronic HCV genotype 1 or 4 infection in pediatric patients 12 years of age and older or weighing at least 30 kg
FDA: Management of moderate to moderately severe pain where an opioid is appropriate.,Off-label: Not commonly used off-label; may be considered for refractory pain conditions.
One tablet (elbasvir 50 mg/grazoprevir 100 mg) orally once daily.
1-2 tablets (hydrocodone 5 mg/acetaminophen 500 mg per tablet) orally every 4-6 hours as needed for pain, maximum 8 tablets per day.
Elbasvir: terminal half-life approximately 24 hours. Grazoprevir: terminal half-life approximately 31 hours. The prolonged half-lives support once-daily dosing and allow for sustained viral suppression.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Elbasvir is metabolized primarily by CYP3A. Grazoprevir is metabolized primarily by CYP3A. Mild oxidation and glucuronidation are minor pathways.
Hydrocodone: primarily hepatic via CYP3A4-mediated N-demethylation to norhydrocodone (active) and O-demethylation via CYP2D6 to hydromorphone (active). Acetaminophen: hepatic via glucuronidation and sulfation; minor oxidation by CYP2E1 to NAPQI (toxic metabolite).
Elbasvir: primarily biliary/fecal (≥90% as metabolites, <1% unchanged in urine). Grazoprevir: primarily biliary/fecal (≥90% as metabolites, <1% unchanged in urine). Renal elimination is negligible for both.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Elbasvir: ≥99.9% bound, primarily to albumin and α1-acid glycoprotein. Grazoprevir: 98.8% bound, primarily to albumin and α1-acid glycoprotein.
<20%; primarily binds to albumin.
Elbasvir: apparent Vd approximately 4.5 L/kg (high, indicating extensive tissue distribution). Grazoprevir: apparent Vd approximately 19 L/kg (very high, likely due to binding to plasma proteins and tissue uptake).
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Elbasvir: absolute bioavailability not determined in humans; oral absorption is high. Grazoprevir: absolute bioavailability approximately 27% after oral administration; absorption is enhanced with food (high-fat meal increases AUC by 1.5-fold).
Oral: 85–95%; rectal: 70–80%.
No dose adjustment required for any degree of renal impairment including end-stage renal disease on dialysis.
GFR 30-59 m L/min: Administer every 6 hours; GFR 10-29 m L/min: Administer every 8 hours; GFR <10 m L/min: Administer every 12 hours; avoid use in severe renal impairment.
Contraindicated in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment required in mild (Child-Pugh A) hepatic impairment.
Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Use not recommended due to hepatotoxicity risk.
Not approved for use in pediatric patients; safety and efficacy not established.
Children ≥2 years: Hydrocodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) plus acetaminophen 10-15 mg/kg/dose (max 500 mg/dose) orally every 4-6 hours as needed; maximum 5 doses per day.
No dose adjustment required; however, clinical studies indicate similar safety and efficacy as in younger adults, but caution is warranted due to potential age-related comorbidities.
Start at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity to opioids and renal clearance decline; monitor for respiratory depression and sedation.
Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV, which may result in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection before initiating treatment.
Risk of addiction, abuse, and misuse; serious, life-threatening or fatal respiratory depression from opioid use; accidental ingestion of acetaminophen can cause acute liver failure; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants.
Risk of hepatitis B virus reactivation,Hepatic decompensation with use in patients with moderate or severe hepatic impairment (Child-Pugh B or C),Elevation of total bilirubin and/or ALT levels,Risk of adverse reactions due to drug interactions (e.g., strong CYP3A inducers/inhibitors)
Addiction, abuse, and misuse; respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risk with concomitant use of CNS depressants; severe hypotension; seizures; serotonin syndrome; adrenal insufficiency; hepatotoxicity (acetaminophen overdose); hypersensitivity reactions; constipation; urinary retention; impaired mental/physical abilities.
Moderate or severe hepatic impairment (Child-Pugh B or C),Use with strong CYP3A inducers (e.g., rifampin, St. John's wort, carbamazepine, phenytoin),Use with certain HIV medications (e.g., efavirenz, etravirine, nevirapine, atazanavir/ritonavir, lopinavir/ritonavir, darunavir/ritonavir, tipranavir/ritonavir),Use with cyclosporine
Hypersensitivity to hydrocodone, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction (e.g., paralytic ileus); use of MAO inhibitors (concurrent or within 14 days).
ZEPATIER can be taken with or without food. No specific food restrictions are required. Grapefruit and grapefruit juice may increase exposure to grazoprevir; although not contraindicated, consider avoiding large quantities.
Avoid grapefruit and grapefruit juice as they may alter metabolism of hydrocodone. Take with food if gastrointestinal upset occurs. Avoid alcohol-containing foods or beverages. No other significant food interactions.
ZEPATIER (grazoprevir/elbasvir) is contraindicated in pregnancy due to the ribavirin component in some regimens. Ribavirin is teratogenic in all trimesters, causing fetal malformations and embryolethality. Grazoprevir/elbasvir alone has no adequate human data, but animal studies show no teratogenicity. However, combination with ribavirin mandates avoidance in pregnancy.
First trimester: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductus arteriosus and oligohydramnios.
No data on human milk excretion. M/P ratio unknown. Ribavirin accumulates in breast milk and is contraindicated during breastfeeding. Grazoprevir/elbasvir: animal studies show excretion in milk; potential for adverse effects. Avoid breastfeeding during treatment and for 7 days after last dose.
No data on M/P ratio; use with caution. Low molecular weight may be excreted into breast milk; monitor infant for sedation or respiratory depression.
No dose adjustment studies in pregnancy. ZEPATIER is not recommended during pregnancy due to ribavirin component. If inadvertently used, no specific dose adjustment; consult maternal-fetal specialist.
No specific dose adjustments required; however, due to increased renal clearance in pregnancy, shortened dosing intervals or higher doses may be needed for adequate analgesia. Monitor clinical response and adjust accordingly.
ZEPATIER (elbasvir/grazoprevir) is indicated for chronic HCV genotypes 1 or 4. Prior to initiation, test for NS5A resistance-associated substitutions (RASs) in genotype 1a. In patients with genotype 1a and baseline NS5A RASs, treatment duration is 16 weeks with ribavirin. Avoid in moderate to severe hepatic impairment (Child-Pugh B or C). Monitor hepatic function closely. Coadministration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine) is contraindicated. Also contraindicated with OATP1B1/3 inhibitors (e.g., cyclosporine) and certain HIV protease inhibitors (e.g., atazanavir, darunavir, lopinavir). Grazoprevir increases serum creatinine due to OATP2B1 inhibition, but this does not reflect true renal function decline.
Co-Gesic is a fixed-dose combination of hydrocodone and acetaminophen. Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen dose should not exceed 4 g. Hydrocodone is a Schedule II controlled substance with abuse potential. Use with caution in patients with respiratory compromise, COPD, or sleep apnea. Avoid concurrent use with other CNS depressants including alcohol. In opioid-tolerant patients, withdrawal may occur if discontinued abruptly.
Take ZEPATIER exactly as prescribed, one tablet once daily with or without food.,Do not stop or skip doses without consulting your healthcare provider.,Inform your doctor of all medications you take, including over-the-counter drugs and herbal supplements, to avoid serious interactions.,Notify your healthcare provider immediately if you experience symptoms of liver problems: yellowing of skin or eyes, dark urine, pale stools, nausea, vomiting, or right upper abdominal pain.,ZEPATIER may elevate creatinine levels without reflecting kidney damage; your doctor will monitor appropriately.,If you have genotype 1a HCV, your doctor will test for specific resistance mutations to determine the correct treatment duration.,Avoid alcohol during treatment as it can exacerbate liver injury.,Use effective contraception during treatment and for 2 weeks after the last dose if you or your partner can become pregnant.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Avoid alcohol while taking this medication due to risk of liver damage and increased sedation.,Do not take other medications containing acetaminophen (Tylenol, many cold/flu products) to avoid exceeding the maximum daily dose (4 grams).,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 children and dispose of unused medication properly (take-back programs preferred).,Do not crush or chew extended-release formulations (if applicable).,Report signs of liver injury (yellowing skin/eyes, dark urine, abdominal pain) or respiratory depression (slow/shallow breathing) immediately.
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 ZEPATIER vs CO-GESIC, answered by our medical review team.
ZEPATIER is a Direct-Acting Antiviral (HCV) that works by ZEPATIER is a fixed-dose combination of elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. Elbasvir inhibits HCV NS5A, disrupting viral replication and assembly. Grazoprevir inhibits the HCV NS3/4A serine protease, preventing cleavage of the HCV polyprotein into mature viral proteins.. CO-GESIC is a Opioid Analgesic Combination that works by CO-GESIC (hydrocodone/acetaminophen) is a combination analgesic. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing prostaglandin synthesis and elevating pain threshold.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ZEPATIER and CO-GESIC 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 ZEPATIER is: One tablet (elbasvir 50 mg/grazoprevir 100 mg) orally once daily.. The standard adult dose of CO-GESIC is: 1-2 tablets (hydrocodone 5 mg/acetaminophen 500 mg per tablet) 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 ZEPATIER and CO-GESIC 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. ZEPATIER is classified as Category C. ZEPATIER (grazoprevir/elbasvir) is contraindicated in pregnancy due to the ribavirin component in some regimens. Ribavirin is teratogenic in all trimesters, causing fetal malformat. CO-GESIC is classified as Category C. First trimester: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductu. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.