ELBASVIR/GRAZOPREVIR
Elbasvir and grazoprevir are antiviral medicines that prevent hepatitis C (HCV) from multiplying in your body.
Elbasvir and grazoprevir is a combination medicine used to treat chronic hepatitis C in adults. elbasvir and grazoprevir is sometimes given together with another drug called ribavirin.
Elbasvir and grazoprevir treats specific genotypes of hepatitis C, and only in certain people. Use only the medications prescribed for you. Do not share your medicine with other people.
Elbasvir and grazoprevir is sometimes used in people who also have HIV. This medicine is not a treatment for HIV or AIDS
Elbasvir and grazoprevir is a combination medicine used to treat chronic hepatitis C in adults. elbasvir and grazoprevir is sometimes given together with another drug called ribavirin.
Elbasvir and grazoprevir treats specific genotypes of hepatitis C, and only in certain people. Use only the medications prescribed for you. Do not share your medicine with other people.
Elbasvir and grazoprevir is sometimes used in people who also have HIV. This medicine is not a treatment for HIV or AIDS
Mechanism of effect
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.
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.
Pharmacokinetics
Absorption:
Not affected by meals.
Distribution:
Elbasvir: Distribution into most tissue including hepatic; Grazoprevir: Predominantly hepatic distribution
Vd: Elbasvir: ~680 L; Grazoprevir: ~1,250 L
Metabolism:
Elbasvir, Grazoprevir: Hepatic (partial oxidative metabolism via CYP3A); metabolites not detected in plasma.
Excretion:
Feces (>90%); urine (<1%)
Time to Peak:
Elbasvir: Median: 3 hours (range: 3 to 6 hours); Grazoprevir: Median: 2 hours (range: 30 minutes to 3 hours)
Half-Life Elimination:
Elbasvir: ~24 hours; Grazoprevir: ~31 hours
Protein Binding:
Elbasvir: >99.9% (albumin, alpha-1 acid glycoprotein); Grazoprevir: 98.8% (albumin, alpha-1 acid glycoprotein)
Not affected by meals.
Distribution:
Elbasvir: Distribution into most tissue including hepatic; Grazoprevir: Predominantly hepatic distribution
Vd: Elbasvir: ~680 L; Grazoprevir: ~1,250 L
Metabolism:
Elbasvir, Grazoprevir: Hepatic (partial oxidative metabolism via CYP3A); metabolites not detected in plasma.
Excretion:
Feces (>90%); urine (<1%)
Time to Peak:
Elbasvir: Median: 3 hours (range: 3 to 6 hours); Grazoprevir: Median: 2 hours (range: 30 minutes to 3 hours)
Half-Life Elimination:
Elbasvir: ~24 hours; Grazoprevir: ~31 hours
Protein Binding:
Elbasvir: >99.9% (albumin, alpha-1 acid glycoprotein); Grazoprevir: 98.8% (albumin, alpha-1 acid glycoprotein)
Drug indications
Labeled Indications:
Chronic hepatitis C: Treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults; used with ribavirin in certain patient populations.
Chronic hepatitis C: Treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults; used with ribavirin in certain patient populations.
Dosage
Usual Adult Dose for Chronic Hepatitis C:
1 tablet orally once a day
Recommended Regimen and Duration of Therapy:
-Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced without baseline nonstructural protein 5A (NS5A) polymorphisms: Elbasvir-grazoprevir for 12 weeks
-Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced with baseline NS5A polymorphisms: Elbasvir-grazoprevir plus ribavirin for 16 weeks
-Genotype 1b, therapy-naive or peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir for 12 weeks
-Genotype 1a or 1b, peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Elbasvir-grazoprevir plus ribavirin for 12 weeks
-Genotype 4, therapy-naive: Elbasvir-grazoprevir for 12 weeks
-Genotype 4, peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir plus ribavirin for 16 weeks
1 tablet orally once a day
Recommended Regimen and Duration of Therapy:
-Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced without baseline nonstructural protein 5A (NS5A) polymorphisms: Elbasvir-grazoprevir for 12 weeks
-Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced with baseline NS5A polymorphisms: Elbasvir-grazoprevir plus ribavirin for 16 weeks
-Genotype 1b, therapy-naive or peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir for 12 weeks
-Genotype 1a or 1b, peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Elbasvir-grazoprevir plus ribavirin for 12 weeks
-Genotype 4, therapy-naive: Elbasvir-grazoprevir for 12 weeks
-Genotype 4, peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir plus ribavirin for 16 weeks
Drug contraindications
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.
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.
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.
Side effects
Side effects requiring immediate medical attention
Along with its needed effects, elbasvir / grazoprevir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking elbasvir / grazoprevir:
Incidence not known
⦁ Dark urine
⦁ fever with or without chills
⦁ light-colored stools
⦁ loss of appetite
nausea and vomiting
⦁ unusual tiredness
⦁ upper stomach pain
⦁ yellow eyes or skin
Side effects not requiring immediate medical attention
Some side effects of elbasvir / grazoprevir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Headache
Along with its needed effects, elbasvir / grazoprevir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking elbasvir / grazoprevir:
Incidence not known
⦁ Dark urine
⦁ fever with or without chills
⦁ light-colored stools
⦁ loss of appetite
nausea and vomiting
⦁ unusual tiredness
⦁ upper stomach pain
⦁ yellow eyes or skin
Side effects not requiring immediate medical attention
Some side effects of elbasvir / grazoprevir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Headache
Interactions
Mibefradil , Delavirdine , pexidartinib , Itraconazole , Bosentan , Primidone , Posaconazole , Gemfibrozil , Rifampin , st. john's wort , Troleandomycin , Ceritinib , conivaptan , nafcillin , ozanimod , cenobamate , Pazopanib , olaparib , lenvatinib , midostaurin , Cerivastatin , Lorlatinib , Simeprevir , Etravirine , Dabrafenib , Eltrombopag , red yeast rice , cobicistat , Fosphenytoin , Idelalisib , Abiraterone , Efavirenz , Tipranavir , Telaprevir , Amprenavir , Fosamprenavir , Eluxadoline , Telithromycin , boceprevir , Indinavir , teriflunomide , Nefazodone , ritonavir , saquinavir , nelfinavir , mitotane , Rosuvastatin , Daclatasvir , Rifabutin , Rifapentine , Darunavir , fluvastatin , Modafinil , Voriconazole , Carbamazepine , Ketoconazole , Clarithromycin , Enzalutamide , Simvastatin , Cyclosporine , Phenobarbital , Phenytoin , Lapatinib , LovastatinAlerts
Oral route (Tablet):
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with elbasvir / grazoprevir. HBV reactivation has been reported in 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 post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
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.
you should not use this medicine if you have moderate or severe liver disease.
Tell your doctor about all your current medicines and any you start or stop using.
Many drugs can interact, and some drugs should not be used together.
If you've ever had hepatitis B, using elbasvir and grazoprevir can cause this virus to
become active or get worse. Tell your doctor if you don't feel well and you have right-sided upper stomach pain, vomiting, loss of appetite, or yellowing of your skin or eyes.
Before taking this medicine
You should not use elbasvir and grazoprevir if you are allergic to elbasvir or grazoprevir, or if you have:
⦁ moderate or severe liver disease.
If you take elbasvir and grazoprevir with ribavirin: There may be other reasons you should not take this combination treatment. Tell your doctor about all your medical conditions.
Many drugs can interact and cause dangerous effects. Some drugs should not be used together with elbasvir and grazoprevir. Your doctor may change your treatment plan if you also use:
cyclosporine;
rifampin;
St. John's wort
HIV or AIDS medication--⦁ atazanavir, darunavir, efavirenz, lopinavir, saquinavir, tipranavir; or
seizure medicine-- carbamazepine, phenytoin.
Tell your doctor if you have ever had:
hepatitis B;
liver problems other than hepatitis C;
HIV (human immunodeficiency virus);
a liver transplant, or if you are waiting to have a liver transplant; or
if you use a blood thinner ( warfarin, Coumadin, Jantoven) and you have routine "INR" or prothrombin time tests.
It is not known whether elbasvir and grazoprevir will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
Elbasvir and grazoprevir is sometimes used in combination with ribavirin. Ribavirin can cause birth defects or death in an unborn baby if the mother or father is using this medicine.
If you are a woman, do not use ribavirin if you are pregnant. You may need to have a negative pregnancy test before taking ribavirin and every month during your treatment.
If you are a man, do not use ribavirin if your sexual partner is pregnant. An unborn baby could be harmed if you have sex with a pregnant woman while you are taking ribavirin.
Both men and women should use at least 2 effective forms of birth control to prevent pregnancy. Keep using 2 forms of birth control for at least 6 months after your last dose of ribavirin.
Tell your doctor right away if a pregnancy occurs while either the mother or the father is using ribavirin.
It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.
Elbasvir and grazoprevir is not approved for use by anyone younger than 18 years old.
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with elbasvir / grazoprevir. HBV reactivation has been reported in 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 post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
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.
you should not use this medicine if you have moderate or severe liver disease.
Tell your doctor about all your current medicines and any you start or stop using.
Many drugs can interact, and some drugs should not be used together.
If you've ever had hepatitis B, using elbasvir and grazoprevir can cause this virus to
become active or get worse. Tell your doctor if you don't feel well and you have right-sided upper stomach pain, vomiting, loss of appetite, or yellowing of your skin or eyes.
Before taking this medicine
You should not use elbasvir and grazoprevir if you are allergic to elbasvir or grazoprevir, or if you have:
⦁ moderate or severe liver disease.
If you take elbasvir and grazoprevir with ribavirin: There may be other reasons you should not take this combination treatment. Tell your doctor about all your medical conditions.
Many drugs can interact and cause dangerous effects. Some drugs should not be used together with elbasvir and grazoprevir. Your doctor may change your treatment plan if you also use:
cyclosporine;
rifampin;
St. John's wort
HIV or AIDS medication--⦁ atazanavir, darunavir, efavirenz, lopinavir, saquinavir, tipranavir; or
seizure medicine-- carbamazepine, phenytoin.
Tell your doctor if you have ever had:
hepatitis B;
liver problems other than hepatitis C;
HIV (human immunodeficiency virus);
a liver transplant, or if you are waiting to have a liver transplant; or
if you use a blood thinner ( warfarin, Coumadin, Jantoven) and you have routine "INR" or prothrombin time tests.
It is not known whether elbasvir and grazoprevir will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
Elbasvir and grazoprevir is sometimes used in combination with ribavirin. Ribavirin can cause birth defects or death in an unborn baby if the mother or father is using this medicine.
If you are a woman, do not use ribavirin if you are pregnant. You may need to have a negative pregnancy test before taking ribavirin and every month during your treatment.
If you are a man, do not use ribavirin if your sexual partner is pregnant. An unborn baby could be harmed if you have sex with a pregnant woman while you are taking ribavirin.
Both men and women should use at least 2 effective forms of birth control to prevent pregnancy. Keep using 2 forms of birth control for at least 6 months after your last dose of ribavirin.
Tell your doctor right away if a pregnancy occurs while either the mother or the father is using ribavirin.
It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.
Elbasvir and grazoprevir is not approved for use by anyone younger than 18 years old.
Points of recommendation
Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using elbasvir and grazoprevir.
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.
You may take elbasvir and grazoprevir with or without food.
Take the medicine at the same time each day.
You will need frequent blood tests to check your liver function.
If you've ever had hepatitis B, using elbasvir and grazoprevir can cause this virus to become active or get worse. You may need frequent liver function tests while using this medicine and for several months after you stop.
You should not stop using elbasvir and grazoprevir suddenly. Stopping suddenly could make your hepatitis C harder to treat with antiviral medicine.
Use all hepatitis C medications as directed and read all medication guides you receive. Do not change your dose or dosing schedule without your doctor's advice.
Every person with chronic hepatitis C should remain under the care of a doctor.
Store at room temperature away from moisture and heat. Keep each tablet in the foil blister pack until you are ready to take it.
Using elbasvir and grazoprevir will not prevent your disease from spreading. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in original blister pack until time of use; protect from moisture.
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.
You may take elbasvir and grazoprevir with or without food.
Take the medicine at the same time each day.
You will need frequent blood tests to check your liver function.
If you've ever had hepatitis B, using elbasvir and grazoprevir can cause this virus to become active or get worse. You may need frequent liver function tests while using this medicine and for several months after you stop.
You should not stop using elbasvir and grazoprevir suddenly. Stopping suddenly could make your hepatitis C harder to treat with antiviral medicine.
Use all hepatitis C medications as directed and read all medication guides you receive. Do not change your dose or dosing schedule without your doctor's advice.
Every person with chronic hepatitis C should remain under the care of a doctor.
Store at room temperature away from moisture and heat. Keep each tablet in the foil blister pack until you are ready to take it.
Using elbasvir and grazoprevir will not prevent your disease from spreading. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in original blister pack until time of use; protect from moisture.
Pregnancy level
HAVE NOT BEEN ESTABLISHEDCombination therapy: Use of a ribavirin-containing regimen is contraindicated in pregnant women and in the male partners of women who are pregnant.
Monotherapy: This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
For combination therapy:
-pregnancy category: X
For monotherapy:
-AU TGA pregnancy category: B1
-US FDA pregnancy category: Not assigned.
Risk summary: No data available on use of this drug in pregnant women to inform a drug-related risk.
Comments:
-If applicable, the manufacturer product information for ribavirin should be consulted regarding use during pregnancy and use in females and males of reproductive potential.
-Effective contraception is required during ribavirin therapy and for 6 months after the last dose; local protocol should be consulted regarding contraception timing.
Animal studies have failed to reveal evidence of teratogenicity or fetal harm. Both components have been shown to cross the placenta in rats and rabbits. There are no controlled data in human pregnancy.
Monotherapy: This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
For combination therapy:
-pregnancy category: X
For monotherapy:
-AU TGA pregnancy category: B1
-US FDA pregnancy category: Not assigned.
Risk summary: No data available on use of this drug in pregnant women to inform a drug-related risk.
Comments:
-If applicable, the manufacturer product information for ribavirin should be consulted regarding use during pregnancy and use in females and males of reproductive potential.
-Effective contraception is required during ribavirin therapy and for 6 months after the last dose; local protocol should be consulted regarding contraception timing.
Animal studies have failed to reveal evidence of teratogenicity or fetal harm. Both components have been shown to cross the placenta in rats and rabbits. There are no controlled data in human pregnancy.
Breast feeding warning
Amounts of each component in breast milk are most likely very low as both components are highly bound to maternal plasma proteins.
LactMed: If the mother requires this drug, it is not a reason to discontinue breastfeeding; some experts recommend against breastfeeding when this drug is used with ribavirin.
-According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the child.
Excreted into human milk: Unknown
Excreted into animal milk: Yes (both components)
Comments:
-The 2 active components have not been studied in nursing mothers receiving treatment for hepatitis C virus infection.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-The manufacturer product information for ribavirin should be consulted (if applicable).
LactMed: If the mother requires this drug, it is not a reason to discontinue breastfeeding; some experts recommend against breastfeeding when this drug is used with ribavirin.
-According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the child.
Excreted into human milk: Unknown
Excreted into animal milk: Yes (both components)
Comments:
-The 2 active components have not been studied in nursing mothers receiving treatment for hepatitis C virus infection.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-The manufacturer product information for ribavirin should be consulted (if applicable).
Related drugs
Sofosbuvir and velpatasvirDrug forms
Zepatier
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