Elbasvir-Grazoprevir

Elbasvir-Grazoprevir is a combination medication used for the treatment of chronic hepatitis C virus genotype 1 or 4 infections in adults and pediatric patients aged 12 years and above and weighing 30 kg and more or for use with ribavirin in certain patient populations.

• Elbasvir-Grazoprevir is available under the following different brand names: Zepatier

Common side effects of Elbasvir-Grazoprevir include:

• fatigue
• headache
• nausea
• abdominal pain
• diarrhea
• shortness of breath
• rash or itching
• irritability
• joint pain
• depression
• anemia

Serious side effects of Elbasvir-Grazoprevir include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat

Rare side effects of Elbasvir-Grazoprevir include:

• right-sided upper stomach pain or swelling
• nausea
• vomiting
• loss of appetite
• confusion
• tiredness
• feeling light-headed
• easy bruising or bleeding
• vomiting blood
• diarrhea
• black or bloody stools
• dark urine
• clay-colored stools
• yellowing of the skin or eyes

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 50 mg/100 mg

Chronic hepatitis C virus infection

Adult and pediatric dosage

• 1 tablet orally once daily; treatment duration and whether to take with or without ribavirin are dependent on genotypes and other patient variables
• Treatment regimen and duration of therapy in patients with or without cirrhosis
• Genotypes 1a
  • Treatment-naïve or PegIFN/RBV-experienced without baseline NS5A polymorphisms: Elbasvir-Grazoprevir for 12 wk
  • Treatment-naïve or PegIFN/RBV-experienced WITH baseline NS5A polymorphisms: Elbasvir-Grazoprevir plus weight-based ribavirin for 16 wk
• Genotype 1b
  • Treatment-naïve or PegIFN/RBV-experienced: Elbasvir-Grazoprevir for 12 wk
• Genotypes 1a or 1b
  • PegIFN/RBV/PI-experienced: Elbasvir-Grazoprevir plus weight-based ribavirin for 12 wk
• Genotype 4
  • Treatment-naïve: Elbasvir-Grazoprevir for 12 wk
  • Peg/IFN/RBV-experienced: Elbasvir-Grazoprevir plus weight-based ribavirin for 16 wk

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Elbasvir-Grazoprevir has severe interactions with at least 25 other drugs.
• Elbasvir-Grazoprevir has serious interactions with at least 38 other drugs.
• Elbasvir-Grazoprevir has moderate interactions with at least 26 other drugs.
• Elbasvir-Grazoprevir has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib
  • voclosporin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk for hepatic decompensation
• If administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen (refer to ribavirin prescribing information)
• Coadministration with OATP1B1/3 inhibitors
• Not a comprehensive list
• May increase the risk for ALT elevations owing to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition
• HIV medications: atazanavir, darunavir, lopinavir, saquinavir, tipranavir
• Immunosuppressants: cyclosporine
• Coadministration with strong CYP3A inducers
• Not a comprehensive list; may lead to loss of virologic response to Elbasvir-Grazoprevir owing to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction
• Anticonvulsants: carbamazepine, phenytoin
• Antimycobacterials: rifampin
• Herbals: St John’s wort
• HIV medications: efavirenz

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Elbasvir-Grazoprevir?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Elbasvir-Grazoprevir?"

Cautions

• Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)
• May increase ALT levels; measure liver enzymes prior to therapy, at treatment week 8, and as clinically indicated; for patients receiving 16 wk of therapy, additional hepatic laboratory testing should be performed at treatment week 12
• Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, reported; in patients with compensated cirrhosis (Child-Pugh A) or evidence of advanced liver disease, such as portal hypertension, more frequent hepatic laboratory testing may be warranted; patients should be monitored for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage; discontinue therapy in patients who develop evidence of hepatic decompensation/failure
• Warnings and precautions (including pregnancy) for ribavirin apply if coadministered
• Risk for adverse reactions or reduced therapeutic effect caused by drug interactions (see Contraindications and Drug Interactions)
• Drug interaction overview
  • Grazoprevir is an OATP1B1/3 substrate, CYP3A4 substrate, and P-gp substrate
  • Elbasvir is a CYP3A4 and P-gp substrate
  • Coadministration with OATP1B1/3 inhibitors that are known or expected to significantly increase grazoprevir plasma concentrations is contraindicated
  • Intestinal P-gp in the absorption of elbasvir and grazoprevir appears to be minimal
  • Coadministration with moderate or strong CYP3A4 inducers may decrease elbasvir and grazoprevir plasma concentrations, leading to the reduced therapeutic effect of Elbasvir-Grazoprevir
  • Coadministration with strong CYP3A inducers or efavirenz is contraindicated
  • Coadministration with moderate CYP3A inducers is not recommended
  • Coadministration with strong CYP3A inhibitors may increase elbasvir and grazoprevir concentrations and is not recommended

Pregnancy and Lactation

• No adequate human data are available
• In animal reproduction studies, no evidence of adverse developmental outcomes was observed with elbasvir or grazoprevir at exposures greater than those in humans at the recommended human dose
• Note: Ribavirin is contraindicated in pregnant women and men whose female partners are pregnant
• Lactation
  • Unknown if distributed in human breast milk
  • Consider the developmental and health benefits of breastfeeding, along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition