Introduction
Efficacious and Effective
Drug regimen | Paritaprevir/ritonavir/ombitasvir/dasabuvir | Ledipasvir/sofosbuvir | Simeprevir/sofosbuvir | Daclatasvir/sofosbuvir | Grazoprevir/elbasvir |
---|---|---|---|---|---|
Drug classes | NS3/4A protease inhibitor/CYP3A pharmacoenhancing agent/NS5A inhibitor/non-nucleoside NS5B palm polymerase inhibitor | NS5A protein inhibitor/NS5B polymerase inhibitor | NS3/A4 protease inhibitor/NS5B polymerase inhibitor | NS5A inhibitor/NS5B polymerase inhibitor | NS3/4A protease inhibitor/NS5A replication complex inhibitor |
Efficacy | |||||
Genotypes | 1 | 1, 4, 5, 6 | 1 | 1, 2, 3 | 1, 4 |
Treatment-naïve non-cirrhotics | SVR = 96–97% | GT 1 SVR = 94–99% GT 4, 5, or 6 SVR = 93–96% | SVR = 93% | GT1 SVR = 96% GT3 SVR = 97% | GT1a SVR = 92% GT1b SVR = 99% |
Treatment-naïve cirrhotics | GT1a SVR = 92% GT1b SVR = 100% | GT 1 SVR = 94% GT 4, 5, or 6 SVR = 93–96% | SVR = 95% | GT3 SVR = 58% | SVR = 97% |
Treatment experienced non-cirrhotics | GT1a SVR = 96% GT1b SVR = 100% | GT 1 SVR = 95% GT 4, 5, or 6 SVR = 93–96% | SVR = 93% | GT3 SVR = 91–100% | SVR = 94% |
Treatment experienced cirrhotics | GT1a SVR = 80–100% GT1b SVR = 86–100% | GT 1 SVR = 86–100% GT 4, 5, or 6 SVR = 93–96% | SVR = 86% (12 weeks) SVR = 100% (24 weeks) | GT3 SVR = 86% | SVR = 95% |
HIV coinfection | GT1a SVR = 91% GT1b SVR = 100% | GT 1 or 4 SVR = 96% | SVR = 77% from observational effectiveness study | GT 1 no cirrhosis SVR = 98% GT 1 cirrhosis SVR = 91% GT3 SVR = 100% | SVR = 96% |
Convenience | |||||
Dosing | Two tablets daily (75/50/12.5 mg) and 250 mg tablet twice daily | One tablet daily (90 mg/400 mg) | 150 mg daily/400 mg daily | 60 mg daily/400 mg daily With strong CYP3A inhibitors—30 mg daily of daclatasvir With moderate CYP3A inducers—90 mg daily of daclatasvir | 100 mg/50 mg daily |
Food requirement | With food | With or without food | With food | With or without food | With or without food |
Need for ribavirin | Use ribavirin except in non-cirrhotic GT1B patients | Can be considered in treatment experienced GT 1 patients with cirrhosis who are eligible or patients with decompensated cirrhosis | No | Can be considered in presence of cirrhosis | Use ribavirin if baseline NS5A resistance-associated variants |
Duration | 12 weeks, except for GT1a with cirrhosis is 24 weeks | Treatment naïve without cirrhosis and baseline HCV RNA <6 million GT1 = 8 weeks Treatment naive with or without cirrhosis GT 1, 4, 5 or 6 = 12 weeks Treatment experienced without cirrhosis GT 1, 4, 5 or 6 = 12 weeks Treatment experienced with compensated cirrhosis GT 1 = 24 weeks or 12 weeks with ribavirin GT 4, 5, 6 = 12 weeks Decompensated cirrhosis GT 1 or 4 = 12 weeks | Treatment naive or experienced without cirrhosis 12 weeks Treatment naive or experienced with cirrhosis 24 weeks | 12 weeks Cirrhosis: GT1: 24 weeks GT2: 16–24 weeks GT3: 24 weeks | 12 weeks 16 weeks in the presence of NS5A resistance-associated variants |
Single tablet regimen | No (first 3 drugs are a combination tablet in addition to dasabuvir tablets) | Yes | No | No | Yes |
Safety | |||||
Adverse events | Common-fatigue, nausea, pruritus, skin reactions, insomnia, asthenia Hepatic decompensation and heart failure in patients with cirrhosis Increased risk of ALT elevations | Common-fatigue, headache, nausea, diarrhea, insomnia Serious symptomatic bradycardia when coadministered amiodarone If administered with RBV-diarrhea, N/V, loss of appetite, asthenia, neutropenia, dizziness, hemolytic anemia (serious) | Common-fatigue, headache, nausea Serious symptomatic bradycardia when the combo is administered with amiodarone Hepatic decompensation and heart failure have also been seen in patients with advanced or decompensated cirrhosis Photosensitivity and rash | Common-fatigue, nausea, headache, diarrhea Serious symptomatic bradycardia when the combo is administered with amiodarone | Common-fatigue, headache, nausea With ribavirin—anemia and headache Serious—ALT elevations |
Special notes | Numerous drug interactions due to ritonavir component | No dosage recommendation can be given for patients with severe renal impairment (CrCl <30 mL/min) or with ESRD due to high exposures of sofosbuvir metabolite | Safety and efficacy has not been established with sofosbuvir in patients with CrCl <30 ml/min or patients on hemodialysis | Safety and efficacy has not been established with sofosbuvir in patients with CrCl <30 ml/min or patients on hemodialysis Dose of daclatasvir may need to be altered when concomitantly used with other CYP3A inhibitors or inducers | Can be used in chronic kidney disease (CKD) stages 4 and 5, including patients on hemodialysis |
Safe
Non-Toxic
Devoid of Drug–Drug Interactions
Paritaprevir/ritonavir/ombitasvir/dasabuvir | Ledipasvir/sofosbuvir | Simeprevir/sofosbuvir | Daclatasvir/sofosbuvir | Grazoprevir/elbasvir | |
---|---|---|---|---|---|
Avoid combination | Alpha 1-antagonist (alfluzosin); Anticonvulsants; antifungals (voriconazole); Antihyperlipidemic (gemfibrozil); Antimycobacterial (rifampin); beta adrenoceptor agonist (salmeterol); corticosteroids (fluticasone); ergot derivatives; ethinyl estradiol containing products; herbal products (St. John’s Wort); HMG-CoA reductase inhibitors (lovastatin and simvastatin); neuroleptic (pimozide); phosphodiesterase-5 inhibitor (sildenafil when used for pulmonary arterial hypertension); sedative/hypnotics (midazolam, triazolam); integrase inhibitors (elvitegravir, dolutegravir); NNRTIs (efavirenz, etravirine, nevirapine, rilpivirine, zidovudine, didanosine); protease inhibitors (darunavir/r, fosamprenavir, ritonavir, lopinavir/r, tipranavir, saquinavir) | Antiarrythmics (amiodarone); anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin); antimycobacterials (rifampin, rifabutin, rifapentine); herbal products (St. John’s Wort); simeprevir; elvitegravir when coadministered with tenofovir disoproxil fumarate, emtricitabine and cobicistat; tipranavir/r | Antiarrythmics (amiodarone); antibiotics (clarithromycin, erythromycin, telithromycin); anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin); antifungals (fluconazole, itraconazole, ketoconazole, osaconazole, voriconazole); Antimycobacterials (rifampin, rifabutin, rifapentine); corticosteroids (dexamethasone); herbal products (milk thistle, St. John’s Wort); GI motility agents (cisapride); elvitegravir; NNRTIs (efavirenz, etravirine, nevirapine); protease inhibitors (atazanavir, fosamprenavir, indinavir, lopinavir/r, ritonavir, saquinavir, tipranavir, darunavir/r) | Antiarrythmics (amiodarone); anticoagulant (dabigatran—depends on renal group); anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin); antimycobacterials (rifampin, rifabutin, rifapentine); herbal products (St. John’s Wort); Tipranavir/r | Anticonvulsants (phenytoin, carbamazepine); antimycobacterials (rifampin); herbal products (St. John’s Wort); NNRTIs (efavirenz, etravirine); protease inhibitors (atazanavir, lopinavir, saquinavir, tipranavir, darunavir); immunosuppressants (cyclosporine); antibiotics (nafcillin); antifungals (ketoconazole); endothelian antagonists (bosentan); integrase inhibitors (elvitegravir coformulated with either tenofovir disoproxil fumarate or alafenamide with emtricitabine and cobicistat); wakefulness agents (modafinil) |
Requires enhanced monitoring | Antiarrythmics (amiodarone, bepredil, disopyramide, flecainide, lidocaine, mexilitine, propafenone, quinidine); diuretic (furosemide); narcotic analgesics (naloxone); proton pump inhibitors; sedative/hypnotic (alprazolam) | Digoxin; NNRTIs (etravirine, nevirapine, efavirenz) | CCBs; Digoxin | Antiarrythmics (digoxin); HMG-CoA reductase inhibitors | HMG-CoA reductase inhibitors (fluvastatin, lovastatin, simvastatin); Immunosuppressants (tacrolimus) |
Requires modification of dose or administration of one or both agents | Antifungal (fluconazole); calcium channel blocker (amlodipine); HMG-CoA reductase inhibitors (atorvastatin, rosuvastatin, and pravastatin); immunosuppressants (cyclospirone, tacrolimus); Phosphodiesterase-5 inhibitor (when used for ED) | H2-receptor antagonists; proton-pump inhibitors; antacids (separate by 4 h); HMG-CoA reductase inhibitors (atorvastatin, rosuvastatin) | HMG-CoA reductase inhibitors; sedative/hypnotics (midazolam, triazolam) | Antibiotics (clarithromycin, erythromycin, nafcillin); antifungals (itraconazole, ketoconazole; posaconazole; voriconazole); antimycobacterials (rifapentine); endothelian antagonists (bosentan); INSTI (elvitegravir with tenofovir disoproxil fumarate, emtricitabine and cobicistat); NNRTIs (efavirenz, etravirine, nevirapine); protease inhibitors (atazanavir boosted with either cobicistat or ritonavir, indinavir, nelfinavir and saquinavir); wakefulness agents (modafinil) | HMG-CoA reductase inhibitors (atorvastatin, rosuvastatin) |