Treatment of genotype 4 chronic hepatitis C infection (HVC) with compensated cirrhosis or without cirrhosis (with ribavirin unless patient is treatment-naïve or cannot tolerate ribavirin).
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.
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%
Distribution: Ritonavir– poor CNS penetration.
Protein Binding: Ombitasvir– 99.9%, paritaprevir– 97–98.6%, ritonavir– >99%
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; negligable urinary excretion; ritonavir– highly metabolized by CYP3A and CYP2D6, 86% excreted in feces (mostly as metabolites), 11.8% excreted in urine.
Half-life: Ombitasvir– 21–25 hr, paritaprevir– 5.5 hr, ritonavir– 4 hr.
TIME/ACTION PROFILE (blood levels)
|ombitasvir PO||unknown||4–5 hr||24 hr|
|paritaprevir PO||unknown||4–5 hr||24 hr|
|ritonavir PO||rapid||4 hr||24 hr|
- Hypersensitivity to any components including previous history of Stevens-Johnson syndrome or toxic epidermal necrolysis from ritonavir;
- Concurrent use of medications that are metabolized by CYP3A4 or strong/moderate inducers of CYP3A4;
- Moderate or severe hepatic impairment;
- OB: When used with ribavirin should not be used in pregnant patients or male patients whose partners are pregnant.
Use Cautiously in:
- Diabetes mellitus;
- Hemophilia (↑ risk of bleeding);
- Structural heart disease, conduction abnormalities, ischemic heart disease, or heart failure (↑ risk of heart block);
- Females with reproductive potential (ethinyl estradiol-containing medications including oral hormonal contraceptives are contraindicated due to ↑ risk of liver impairment; effective alternative contraception is recommended);
- Concurrent HIV infection (additional HIV-suppressive regimen required);
- Receiving immunosuppressant or chemotherapy medications (↑ risk of hepatitis B virus reactivation);
- OB: If used without ribavirin consider maternal benefits and possible adverse effects on the fetus;
- Lactation: Consider maternal benefits and possible adverse effects on infants; breast feeding not recommended in concurrently HIV-infected patients;
- Rep: Women of reproductive potential;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: fatigue (↑ when used with ribavirin), insomnia (↑ when used with ribavirin), weakness (↑ when used with ribavirin)
GI: nausea, HEPATOTOXICITY, ↑ bilirubin
Metabolic: HYPERSENSITIVITY REACTIONS INCLUDING ANGIOEDEMA
Misc: hepatitis B virus reactivation
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- ↑ levels and risk of serious adverse reactions with alfuzosin (hypotension); dihydroergotamine, ergotamine, or methylergonovine (ergot toxicity); atorvastatin, lovastatin, or simvastatin (myopathy/rhabdomyolysis); pimozide (arrhythmias); efavirenz (↑ liver enzymes); sildenafil (when used for pulmonary hypertension ↑ risk of visual disturances/hypotension/priapism/syncope); triazolam (↑ sedation/respiratory depression); ethinyl estradiol containing preparations including oral hormonal contraceptives (↑ liver enzymes); colchicine (serious or life-threatening reactions in patients with renal or hepatic impairment); ranolazine (serious or life-threatening reactions); dronedarone (arrhythmias); everolimus, sirolimus, or tacrolimus (serious or life-threatening immunosuppressant adverse reactions); and lurasidone (serious or life-threatening reactions); concurrent use contraindicated.
- Levels and antiviral effectiveness are ↓ by carbamazepine, phenobarbital, phenytoin, and rifampin; concurrent use contraindicated.
- ↑ levels and risk of digoxin toxicity; ↓ digoxin dose by 30–50%, monitor carefully.
- ↑ levels and risk of adverse cardiovascular reactions with amiodarone, disopyramide, flecainide, lidocaine, mexiletine, propafenone, and quinidine; careful monitoring recommended.
- ↑ levels and risk of adverse reactions with ketoconazole (daily dose of ketoconazole should not exceed 200 mg).
- ↓ levels and effectiveness of voriconazole; concurrrent use is not recommended.
- ↑ levels and risk of adverse reactions with quetiapine; ↓ quetiapine dose to ⅙th and monitor carefully, consider alternative anti-HCV treatments).
- ↑ levels and risk of hypotension with amlodipine, nifedipine, diltiazem, and verapamil; ↓ dose of amlodipine by ≥50%.
- ↑ levels and effects of furosemide; monitor and adjust dose.
- Concurrent use with atazanavir, atazanavir/ritonavir, or lopinair/ritonavir ↑ levels of paritaprevir; concurrent use is not recommended.
- ↓ levels and may ↓ effectiveness of darunavir; darunavir (800 mg once daily) without ritonavir should be taken at the same time as ombitasvir/paritaprevir/ritonavir.
- ↑ levels and risk of adverse cardiovascular reactions with rilpivirine; concurrent use is not recommended.
- ↑ levels and risk of adverse muscular reactions with pravastatin; pravastatin dose should not exceed 40 mg/day.
- ↑ levels and risk of adverse reactions with cyclosporine; ↓ cyclosporine dose to ⅕th, monitor and readjust carefully.
- ↑ levels and risk of adverse cardiovascular reactions with salmeterol; Concurrent use is not recommended.
- ↑ levels of buprenorphine; monitor for sedation/cognitive impairment.
- ↑ levels of hydrocodone; ↓ hydrocodone dose by 50% and monitor for sedation and respiratory depression.
- ↓ levels and effectiveness of omeprazole; ↑ dose of omeprazole if necesssary, but should not exceed 40 mg/day.
- ↑ levels and effects of alprazolam; monitor for sedation/cognitive impairment and adjust dose.
- ↓ levels and effectiveness of diazepam; ↑ dose of diazepam, if necesssary.
- ↑ levels of valsartan, losartan, and candesartan; ↓ dose of angiotensin II receptor blocker and monitor for hypotension and renal impairment.
- ↑ risk of lactic acidosis with metformin; concomitant use in patients with renal or hepatic impairment not recommended.
- May ↓ levels and effectiveness of carisoprodol or cyclobenzaprine; ↑ dose of carisoprodol or cyclobenzaprine, if necesssary.
Levels and antiviral effectiveness are ↓ by St. John's wort ; concurrent use contraindicated.
PO: (Adults) Two tablets (each tablet containing ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg) once daily for 12 wk given concurrently with ribavirin 500 mg twice daily in patients <75 kg or 600 mg twice daily in patients ≥75kg; may be used without ribavirin in treatment-naïve patients without cirrhosis or patients who do not tolerate ribavarin.
Tablets: ombitasvir 12.5 mg/paritaprevir 75 mg/ritonavir 50 mg
- Monitor signs of hepatitis (jaundice, fatigue, anorexia, pruritus, weakness, nausea, vomiting, discolored feces) 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 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.
- May cause ↓ hemoglobin requiring dose reduction.
- Risk for injury (Indications)
- PO: Administer 2 tablets once daily, in the morning, with a meal without regard to fat or calorie content. Usually given in combination with ribavirin.
- Instruct patient to take Technivie as directed. Take missed dose within 12 hrs; if more than 12 hrs 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 Technivie 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 6 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.
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