Drug information of Ombitasvir, Paritaprevir, and Ritonavir

Ombitasvir, Paritaprevir, and Ritonavir

Drug group:

It is used to treat hepatitis C infection.

Mechanism of effect

Combines 2 direct-acting hepatitis C virus antiviral agents with distinct mechanisms of action. Ombitasvir inhibits HCV NS5A, and interferes with viral RNA replication and virion assembly. Paritaprevir inhibits HCV NS3/4A protease and interferes with HCV coded polyprotein cleavage necessary for viral replication.

Ritonavir is not active against HCV. Ritonavir is a potent CYP3A inhibitor that increases peak and trough plasma drug concentrations of paritaprevir and overall drug exposure.

Pharmacokinetics

Absorption

Well absorbed when administered with food

Distribution

Ombitasvir: Vd: 173 L

Paritaprevir: Vd: 103 L

Ritonavir: Vd: 21.5 L

Metabolism

Ombitasvir: Metabolized by amide hydrolysis and oxidative metabolism

Paritaprevir: Metabolized by CYP3A4 and to a lesser extent CYP3A5

Ritonavir: Metabolized by CYP3A and to a lesser extent CYP2D6

Excretion

Ombitasvir: Feces (90.2%, mainly as unchanged drug); urine (1.91%, mainly as unchanged drug)

Paritaprevir: Feces (88%, mainly as metabolites); urine (8.8%, mainly as metabolites)

Ritonavir: Feces (86.4%); urine (11.3%)

Time to Peak

Ombitasvir, paritaprevir, ritonavir: 4 to 5 hours

Half-Life Elimination

Ombitasvir: 21 to 25 hours; Paritaprevir: 5.5 hours; Ritonavir: 4 hours

Protein Binding

Ombitasvir: 99.9%; Paritaprevir: ~98%; Ritonavir: >99%

Drug indications

Chronic hepatitis C

Dosage

Treatment of chronic hepatitis C virus (HCV) genotype 4 infection without cirrhosis or with compensated cirrhosis, in combination with ribavirin:

Two tablets once daily (every morning) for 12 weeks, in combination with ribavirin.

Drug contraindications

Hypersensitivity to this drug , Concurrent use of strong CYP3A inducers

-Hypersensitivity to ritonavir (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome) or any component of the formulation;
-moderate to severe hepatic impairment (Child-Pugh class B or C);
-concurrent use of drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events; -concurrent use of moderate or strong inducers of CYP3A.
-Concurrent use of drugs that are contraindicated include, but are not necessarily limited to: Alfuzosin, apalutamide, atorvastatin, colchicine (in patients with renal and/or hepatic impairment), carbamazepine, cisapride, dronedarone, ergot derivatives (ergonovine, ergotamine, dihydroergotamine, methylergonovine), ethinyl estradiol-containing products, efavirenz, everolimus, lomitapide, lovastatin, lurasidone, midazolam (oral), phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (when used for the treatment of pulmonary arterial hypertension [eg, Revatio]), simvastatin, sirolimus, St John's wort, tacrolimus, triazolam. 

Side effects

anemia , Insomnia , nausea , Hypersensitivity , liver failure , itching , tiredness , allergic reactions

Asthenia, Fatigue , insomnia , Allergic skin reaction , pruritus ,Nausea, Anemia, decreased hemoglobin,Increased serum alanine aminotransferase, Anaphylaxis, erythema multiforme, hepatic failure (in patients with underlying cirrhosis; FDA Safety Alert, October 22, 2015), hypersensitivity reaction (including angioedema), liver decompensation (in patients with underlying cirrhosis;), reactivation of HBV

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Alerts

-Hepatic decompensation and hepatic failure, including liver transplantation and fatal cases, have been reported with ombitasvir, paritaprevir, and ritonavir, with or without ribavirin;

-Elevations of ALT (>5 × ULN) have been reported. 

-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.

-Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy;

- Risk of HIV-1 protease inhibitor drug resistance: Ritonavir, a component of the product, is also an HIV-1 protease inhibitor. In HCV/HIV co-infected patients, ritonavir can select for HIV-1 protease inhibitor resistance-associated substitutions. Any HCV/HIV-1 co-infected patients should also be taking a suppressive antiretroviral regimen to reduce resistance risk.

Points of recommendation

-Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modifications of antidiabetic therapy may be necessary .

-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.

-Hepatitis B surface antigen and hepatitis B core antibody prior to initiation; in patients with serologic evidence of hepatitis B virus (HBV) infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during posttreatment follow-up.

Pregnancy level

HAVE NOT BEEN ESTABLISHED

 No adequate data available on use of this drug in pregnant women to inform a drug-related risk.

Breast feeding warning

-Neither ombitasvir nor paritaprevir has 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 product.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this product or the mother's underlying condition should be considered.

Drug forms

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