Version May 2024
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment. HBV reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Note: Compensated cirrhosis is defined as Child-Pugh class A (AASLD/IDSA 2021).
Chronic hepatitis C:
Genotype 1a:
Note: Prior to initiating therapy, NS5A resistance-associated substitution (RAS) testing may be useful to determine if clinically important resistance exists necessitating use of an alternative regimen (AASLD/IDSA 2021).
Treatment-naive without cirrhosis (alternative agent): Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks (AASLD/IDSA 2021).
Post kidney transplantation, treatment-naive or nondirect-acting antiviral–experienced patients without cirrhosis or with compensated cirrhosis (alternative agent): Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks. Note: Reserve use for patients without baseline NS5A RASs for elbasvir (AASLD/IDSA 2021).
Genotype 1b:
Treatment-naive without cirrhosis or with compensated cirrhosis: Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks; 8 weeks may be considered for patients with mild fibrosis without cirrhosis (AASLD/IDSA 2021).
Post kidney transplantation, treatment-naive or nondirect-acting antiviral–experienced patients without cirrhosis or with compensated cirrhosis (alternative agent): Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks. Note: Reserve use for patients without baseline NS5A RASs for elbasvir (AASLD/IDSA 2021).
Genotype 4:
Treatment-naive without cirrhosis or with compensated cirrhosis: Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks (AASLD/IDSA 2021).
Post kidney transplantation, treatment-naive or nondirect-acting antiviral–experienced patients without cirrhosis or with compensated cirrhosis (alternative agent): Oral: 1 tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily for 12 weeks. Note: Reserve use for patients without baseline NS5A RASs for elbasvir (AASLD/IDSA 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl ≤50 mL/minute: No dosage adjustment necessary. If used with concomitant ribavirin, refer to ribavirin monograph for dosage adjustments.
End-stage renal disease (ESRD) and hemodialysis (not removed by hemodialysis): No dosage adjustment necessary.
Preexisting hepatic impairment:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C) or prior hepatic decompensation: Use is contraindicated.
Hepatotoxicity during treatment:
Asymptomatic increases in ALT <10-fold: Closely monitor with repeat testing every 2 weeks. If persistent elevation remains, consider stopping therapy (AASLD/IDSA 2021).
<10-fold increase in ALT from baseline with weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or INR: Discontinue direct-acting antiviral (AASLD/IDSA 2021).
≥10-fold increase in ALT from baseline at any time during treatment: Discontinue direct-acting antiviral therapy, especially with signs and symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR (AASLD/IDSA 2021).
Refer to adult dosing.
(For additional information see "Elbasvir and grazoprevir: Pediatric drug information")
Chronic hepatitis C, genotype 1a:
Children ≥12 years of age or weighing ≥30 kg and Adolescents: Elbasvir 50 mg and grazoprevir 100 mg per tablet:
Treatment-naive or peginterferon alfa + ribavirin treatment–experienced without baseline NS5A resistance-associated substitutions (RASs) for elbasvir: Oral: 1 tablet once daily for 12 weeks.
Treatment-naive or peginterferon alfa + ribavirin treatment-experienced with baseline NS5A RASs for elbasvir: Oral: 1 tablet once daily for 16 weeks in combination with ribavirin.
Peginterferon alfa + ribavirin + NS3/4A protease inhibitor treatment-experienced: Oral: 1 tablet once daily for 12 weeks in combination with ribavirin. Note: The optimal treatment regimen for peginterferon alfa + ribavirin + NS3/4A protease inhibitor treatment-experienced patients with NS5A RASs at positions 28, 30, 31, or 93 has not been established.
Chronic hepatitis C, genotype 1b:
Children ≥12 years of age or weighing ≥30 kg and Adolescents: Elbasvir 50 mg and grazoprevir 100 mg per tablet:
Treatment-naive or peginterferon alfa + ribavirin treatment-experienced: Oral: 1 tablet once daily for 12 weeks.
Peginterferon alfa + ribavirin + NS3/4A protease inhibitor treatment-experienced: Oral: 1 tablet once daily for 12 weeks in combination with ribavirin.
Chronic hepatitis C, genotype 4:
Children ≥12 years of age or weighing ≥30 kg and Adolescents: Elbasvir 50 mg and grazoprevir 100 mg per tablet:
Treatment-naive: Oral: 1 tablet once daily for 12 weeks.
Peginterferon alfa + ribavirin treatment-experienced: Oral: 1 tablet once daily for 16 weeks in combination with ribavirin.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥12 years or weighing ≥30 kg and Adolescents:
Any degree of renal impairment: No dosage adjustment necessary.
Hemodialysis: No dosage adjustment necessary.
Preexisting hepatic impairment:
Children ≥12 years or weighing ≥30 kg and Adolescents:
Mild impairment: No dosage adjustment necessary.
Moderate or severe impairment: Use is contraindicated.
History of prior hepatic decompensation: Use is contraindicated.
Hepatotoxicity during treatment:
Children ≥12 years or weighing ≥30 kg and Adolescents:
ALT >10 times ULN: Consider discontinuing therapy if ALT levels remain persistently >10 times ULN.
Any ALT elevation accompanied by signs/symptoms of hepatic inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR: Discontinue therapy.
Hepatic decompensation/failure: Discontinue therapy.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Nervous system: Fatigue (11%)
1% to 10%:
Hepatic: Increased serum alanine aminotransferase (1%)
Nervous system: Headache (10%)
<1%:
Hematologic & oncologic: Decreased hemoglobin
Hepatic: Increased serum bilirubin
Frequency not defined: Hepatic: Acute hepatic failure (FDA Safety Alert, August 28, 2019), severe hepatic disease (FDA Safety Alert, August 28, 2019)
Postmarketing:
Hypersensitivity: Angioedema
Infection: Reactivation of HBV
Moderate or severe hepatic impairment (Child-Pugh class B or C); history of prior hepatic decompensation; concurrent use with OATP1B1/3 inhibitors that are known or expected to significantly increase grazoprevir plasma concentrations and strong inducers of CYP3A. Concurrent use of drugs that are contraindicated include, but are not necessarily limited to: atazanavir, carbamazepine, cyclosporine, darunavir, efavirenz, lopinavir, phenytoin, rifampin, saquinavir, St. John's wort, tipranavir. If used with ribavirin, contraindications of ribavirin also apply. See ribavirin prescribing information.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling (not in US labeling): Hypersensitivity to elbasvir, grazoprevir, or any component of the formulation. If used with sofosbuvir, contraindications of sofosbuvir also apply. See sofosbuvir prescribing information.
Concerns related to adverse effects:
• ALT elevations: ALT elevations (>5 times ULN) have been observed generally at week 8 or beyond; changes have been mostly asymptomatic and resolved with ongoing or completed therapy. Females, Asian patients, and patients ≥65 years of age may be at greater risk for ALT changes. Patients should report fatigue, weakness, decreased appetite, nausea/vomiting, jaundice, or discolored feces. Monitor liver function tests prior to therapy, at treatment week 8, and as clinically indicated. Consider discontinuing therapy if ALT levels remain persistently >10 times ULN. Discontinue therapy if accompanied by signs/symptoms of hepatic inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
Disease-related concerns:
• Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic therapy may be necessary (Ciancio 2018; Dawood 2017; Hum 2017).
• Hepatic impairment: Cases of hepatic decompensation and failure, some fatal, have been reported in patients without cirrhosis and in patients with baseline cirrhosis with and without moderate or severe liver impairment (Child-Pugh class B or C). Use is contraindicated in moderate or severe impairment (Child-Pugh class B or C) and with a history of prior hepatic decompensation. Monitor hepatic function tests and for signs and symptoms of hepatic decompensation more frequently in patients with compensated cirrhosis (Child-Pugh class A) or evidence of advanced liver disease (eg, portal hypertension); discontinue if hepatic decompensation or failure develops.
• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of treatment; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.
Other warnings/precautions:
• Resistance testing prior to treatment initiation in HCV genotype 1a: Testing patients with HCV genotype 1a infection for the presence of virus with NS5A resistance-associated polymorphisms is recommended prior to treatment initiation to determine regimen and duration. Sustained virologic response rates were lower after 12 weeks in genotype 1a-infected patients with one or more baseline NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Zepatier: Elbasvir 50 mg and grazoprevir 100 mg
No
Tablets (Zepatier Oral)
50-100 mg (per each): $312.00
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Zepatier: Elbasvir 50 mg and grazoprevir 100 mg [DSC]
Oral: Administer without regard to meals.
Oral: Administer without regard to meals.
Hepatitis C, chronic: Treatment of chronic hepatitis C virus genotype 1 or 4 infection in adults and pediatric patients ≥12 years of age or ≥30 kg; used with ribavirin in certain patient populations.
Substrate of CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP3A4 (weak), OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification
Atorvastatin: Elbasvir and Grazoprevir may increase the serum concentration of Atorvastatin. Management: Limit the adult dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Use the lowest atorvastatin dose necessary and monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Risk D: Consider therapy modification
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Cobicistat: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fluvastatin: Elbasvir and Grazoprevir may increase the serum concentration of Fluvastatin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Lopinavir: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Lovastatin: Elbasvir and Grazoprevir may increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Red Yeast Rice: Elbasvir and Grazoprevir may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
RifAMPin: May increase the serum concentration of Elbasvir and Grazoprevir. RifAMPin may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Rosuvastatin: Elbasvir and Grazoprevir may increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day during coadministration with elbasvir/grazoprevir. Monitor closely for evidence of rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
Saquinavir: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Simvastatin: Elbasvir and Grazoprevir may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
St John's Wort: May decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Tacrolimus (Systemic): Direct Acting Antiviral Agents (HCV) may decrease the serum concentration of Tacrolimus (Systemic). Direct Acting Antiviral Agents (HCV) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Tipranavir: May increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Patients with hepatitis C virus (HCV) infection should be treated before considering pregnancy to optimize maternal health and reduce the risk of HCV transmission (AASLD/IDSA 2021).
If used in combination with ribavirin, all warnings related to the use of ribavirin and contraception should be followed. Refer to the ribavirin monograph for additional information.
Outcome data following maternal use of direct-acting antiviral (DAA) medications during pregnancy are limited. Use of a DAA is not currently recommended for the purpose of reducing mother to child transmission of hepatitis C virus due to a lack of safety and efficacy data. The decision to continue treatment in a patient who becomes pregnant while taking a DAA should be individualized after considering the potential benefits and risks of therapy. DAA medications should not be initiated during pregnancy outside of clinical trials until safety and efficacy data are available (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).
If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy should be followed. Refer to the ribavirin monograph for additional information.
It is not known if elbasvir or grazoprevir are present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
Breastfeeding is not linked to the spread of hepatitis C virus; however, if nipples are cracked or bleeding, breastfeeding is not recommended (milk should be expressed and discarded) (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).
Pretreatment assessment: Evaluate for advanced hepatic fibrosis and hepatocellular carcinoma. Confirm vaccination against hepatitis A and B (AASLD/IDSA 2021). Assess for potential drug-drug interactions and patient's readiness for adherence.
Laboratory tests recommended at any time before starting therapy:
Quantitative hepatitis C virus (HCV) RNA (HCV viral load), HCV genotype and subtype, HIV antigen/antibody (AASLD/IDSA 2021).
Assessment for active hepatitis B virus (HBV) coinfection: HBV surface antigen (HBsAg); HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs); if evidence of hepatitis B viral coinfection, HBV DNA level should be drawn. HBsAg-positive patients not already receiving HBV suppressive therapy should be either: Initiated on prophylactic HBV antiviral therapy (for those with low or undetectable HBV DNA levels), which should be continued until 12 weeks after completion of HCV therapy, OR monitor HBV DNA levels monthly during and immediately after HCV therapy (AASLD/IDSA 2021).
Laboratory tests recommended within 6 months prior to starting therapy: CBC, INR, hepatic function panel (serum albumin, total and direct bilirubin, ALT, AST, alkaline phosphatase), eGFR (AASLD/IDSA 2021).
Laboratory tests immediately prior to starting therapy:
Serum pregnancy test for patients of childbearing potential.
Patients with genotype 1a require baseline NS5A resistance-associated substation testing for presence of high-fold changes (eg, changes at amino acid positions 28, 30, 31, and 93) (AASLD/IDSA 2021).
On-treatment monitoring:
LFTs should be monitored at 8 weeks and again at 12 weeks if receiving 16 weeks of treatment along with periodic monitoring of liver function if required, and assessment for presence of symptoms of liver dysfunction (eg, weakness, nausea, vomiting, jaundice, or significantly elevated bilirubin, alkaline phosphatase, or INR) (AASLD/IDSA 2021).
In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (AASLD/IDSA 2021; Ciancio 2018; Dawood 2017; Hum 2017); in patients taking warfarin, monitor INR during and post therapy (AASLD/IDSA 2021).
Post treatment assessment of cure: Quantitative HCV viral load testing 12 or more weeks after completion of therapy to document sustained virologic response and liver transaminases (AASLD/IDSA 2021).
Elbasvir is an inhibitor of HCV NS5A, which is essential for viral replication and virion assembly.
Grazoprevir is an inhibitor of HCV NS3/4A protease, necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication.
Absorption: Not affected by meals.
Bioavailability: Elbasvir: 32%; Grazoprevir: 27%
Distribution: Elbasvir: Distribution into most tissue including hepatic; Grazoprevir: Predominantly hepatic distribution
Vd: Elbasvir: ~680 L; Grazoprevir: ~1,250 L
Protein binding: Elbasvir: >99.9% (albumin, alpha-1 acid glycoprotein); Grazoprevir: 98.8% (albumin, alpha-1 acid glycoprotein)
Metabolism: Elbasvir, Grazoprevir: Hepatic (partial oxidative metabolism via CYP3A); metabolites not detected in plasma
Half-life elimination: Elbasvir: ~24 hours; Grazoprevir: ~31 hours
Time to peak: Elbasvir: Median: 3 hours (range: 3 to 6 hours); Grazoprevir: Median: 2 hours (range: 30 minutes to 3 hours)
Excretion: Feces (>90%); urine (<1%)
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