Treatment of (with or without ribavirin) genotype 1 chronic hepatitis C infection (HCV) including those with compensated cirrhosis.
Ombitasvir–is an inhibitor of HCV NS5A which is necessary for RNA replication and virion assembly. Paritaprevir–is an inhibitor of NS3/4A protease an enzyme necessary for viral replication. Ritonavir is not active against HCV, but inhibits CYP3A resulting in ↑ blood levels and effectiveness of paritaprevir. Dasabuvir–inhibits RNA-dependent RNA polymerase necessary for viral genome replication.
Decreased levels of HCV with sustained virologic response and lessened sequelae of chronic HCV infection.
Absorption: Well absorbed following oral administration: ombitasvir–48%, paritaprevir–53%, dasabuvir–70%.
Distribution: Ritonavir–poor CNS penetration.
Protein Binding: Ombitasvir–99.9%, paritaprevir–97–98.6%, ritonavir–>99%, dasabuvir–>99.5%.
Metabolism and Excretion: Ombitasvir–metabolized by amide hydrolysis and then oxidative metabolism, excreted mainly in feces mostly as unchanged drug, minimal urinary excretion; paritaprevir–primarily metabolized by CYP3A, 88% excreted in feces mostly as metabolites; negligible urinary excretion; ritonavir–highly metabolized by CYP3A and CYP2D6, 86% excreted in feces (mostly as metabolites), 11.8% excreted in urine, dasabuvir–mostly metabolized by CYP2C8 and smaller amounts by CYP3A, 95% excreted in feces (26% as unchanged drug), minimal urinary excretion.
May cause fluctuations in INR when used with warfarin; closely monitor INR.
Levels and antiviral effectiveness are ↓ by St. John's wort; concurrent use contraindicated.
PO (Adults) Genotype 1a without cirrhosis–Two tablets (each tablet containing ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg) once daily with dasabuvir 250 mg twice daily with ribavirin for 12 wk; Genotype 1a with compensated cirrhosis–Two tablets (each tablet containing ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg) once daily with dasabuvir 250 mg twice daily with ribavirin for 24 wk (some patients may respond to 12 wk); Genotype 1b with or without compensated cirrhosis–Two tablets (each tablet containing ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg) once daily with dasabuvir 250 mg twice daily for 12 wk; Liver transplant patients–Two tablets (each tablet containing ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg) once daily with dasabuvir 250 mg twice daily with ribavirin for 24 wk.
Tablets (Viekira Pak): ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg (copackaged with dasabuvir 250 mg in a 28–day convenience pak separated into weekly amounts)
Monitor signs of hepatitis (jaundice, fatigue, anorexia, pruritus) during therapy.
Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or Toxic Epidermal Necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of worsening liver disease (ascites, hepatic encephalopathy, variceal hemorrhage, increases in direct serum bilirubin).
Monitor for signs and symptoms of hepatitis B reactivation (jaundice, dark urine, light colored stools, fatigue, weakness, loss of appetite, nausea, vomiting, stomach pain) during therapy.
Lab Test Considerations:
Determine current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV therapy. In patients with HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation (rapid ↑ in serum HBV DNA level) during HCV therapy and during post-therapy follow-up.
For patients with compensated cirrhosis: Monitor liver function tests including direct bilirubin levels at baseline and during first 4 wk of therapy and as clinically indicated. Signs of hepatic decompensation usually include ↑ bilirubin without ↑ ALT, and ascites, hepatic encephalopathy, variceal hemorrhage. Discontinue therapy if signs of hepatic decompensation occur.
Monitor liver function tests prior to and during first 4 wks of therapy. If ALT is ↑, repeat test and monitor closely. Discontinue therapy if ALT levels are persistently ↑ >10 × upper limit of normal or if accompanied by signs of liver inflammation or ↑ direct bilirubin, alkaline phosphatase, or INR.
May cause ↑ serum bilirubin; peaks by wk 1 of therapy and not associated with ↑ ALT.
PO Administer 2 ombitasvir/paritaprevir/ritonavir 12.5/75/50 mg tablets once daily (in the morning) and 1 dasabuvir 250 mg tablet twice daily (morning and evening) with a meal without regard to fat or calorie content. Usually given in combination with ribavirin.
Instruct patient to take Viekira Pak as directed. Take missed doses of ombitasvir/paritaprevir/ritonavir within 12 hrs or of dasabuvir within 6 hrs; if more than 12 hrs or 6 hrs, respectively, since missed dose, skip dose and take next dose at scheduled time; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional promptly if signs and symptoms of liver dysfunction (fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, discolored feces) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products, especially St. John's wort. Medications containing ethinyl estradiol must be stopped; if taking for birth control, another method must be used.
Rep: Inform patient about teratogenic effects of Viekira Pak and ribavirin. Instruct women with childbearing potential, and men, to use 2 forms of effective non-hormonal contraception (ethinyl estradiol-containing medications including oral hormonal contraceptives are contraindicated due to ↑ risk of liver impairment; effective alternative contraception is recommended) during and for at least 2 mo following conclusion of therapy. Men must use a condom. Avoid breast feeding during use. Advise patient to notify health care professional if pregnancy occurs.
Protection from liver damage caused by chronic hepatitis C infection; decreases viral load.
ombitasvir/paritaprevir/ritonavir/dasabuvir is a sample topic from the Davis's Drug Guide.
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