Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection

Figures & data

Table 1 Phase III clinical trials of PrOD

Trial name and design	Genotype, treatment history	N	Interventions	SVR12 rate (%)	Virologic failure (%)	Discontinuation due to ADEs (%)	Serious adverse events (%)
Noncirrhotic patients
PEARL-II^Citation19 Open-label	1b, experienced	179	PrOD + RBV ×12 weeks	Overall: 96.6 Prior relapse: 100 Prior partial response: 96.0 Prior null response: 93.5	During treatment: 0 Relapse: 0	2.2	2.2
PEARL-III^Citation18 Double-blind, placebo-controlled	1b, naïve	419	PrOD + RBV ×12 weeks	99.5	During treatment: 0.5 Relapse: 0	0	1.9
			PrOD + placebo ×12 weeks	99.0	During treatment: 0 Relapse: 0	0	1.9
PEARL-IV^Citation18 Double-blind, placebo-controlled	1a, naïve	305	PrOD + RBV ×12 weeks	97.0	During treatment: 1.0 Relapse: 1.0	0	3.0
			PrOD + placebo ×12 weeks	90.2	During treatment: 2.9 Relapse: 5.2	1	0.5
SAPPHIRE-I^Citation16 Double-blind, placebo-controlled	1a and 1b, naïve	631	PrOD + RBV ×12 weeks Placebo ×12 weeks	Overall: 96.2 1a: 95.3 1b: 98.0	During treatment: 0.2 Relapse: 1.5	0.6 (placebo: 0.6)	2.1 (placebo: 0)
SAPPHIRE-II^Citation17 Double-blind, placebo-controlled	1a and 1b, experienced	394	PrOD + RBV ×12 weeks Placebo ×12 weeks	Overall: 96.3 1a: 96.0 1b: 96.7 Prior relapse: 95.3 Prior partial response: 100 Prior null response: 95.2	During treatment: 0 Relapse: 2.4	1.0 (placebo: 0)	2.0 (placebo: 1.0)
GIFT-I (substudy 1)^Citation20 Double-blind, placebo-controlled	1b, naïve and experienced	321	PrOD ×12 weeks Placebo ×12 weeks	Overall: 94.9 Naïve: 94.2 Experienced: 96.1	During treatment: 0.5 Relapse: 2.3	0.9 (placebo: 0)	3.3 (placebo: 1.9)
Cirrhotic patients
TURQUOISE-II^Citation21 Open-label	1a and 1b, naïve and experienced	380	PrOD + RBV ×12 weeks	1a, naïve: 92.2 1b, naïve: 100 1a, prior relapse: 93.3 1a, prior partial response: 100 1a, prior null response: 80.0 1b, prior relapse: 100 1b, prior partial response: 85.7 1b, prior null response: 100	During treatment: 0.5 Relapse: 5.9	2	6.2
			PrOD + RBV ×24 weeks	1a, naïve: 92.9 1b, naïve: 100 1a, prior relapse: 100 1a, prior partial response: 100 1a, prior null response: 92.9 All 1b prior treatment: 100	During treatment: 1.7 Relapse: 0.6	2	4.7
GIFT-I (substudy 2)^Citation20 Open-label	1b, naïve and experienced	42	PrOD ×12 weeks	Overall: 90.5 Naïve: 100 Experienced: 87.9	During treatment: 2.4 Relapse: 4.8	2.4	4.8

Abbreviations: ADEs, adverse drug events; RBV, ribavirin; SVR12, sustained virologic response at 12 weeks after the end of treatment; PrOD, paritaprevir/ritonavir/ombitasvir plus dasabuvir.

Table 2 PrOD drug–drug interactions and recommendations

Drug class	Studied medications	Recommendation with PrOD regimen coadministration
Contraindications
Alpha-1 adrenergic antagonists	Alfuzosin	Contraindicated due to risk of hypotension
Anticonvulsants	Carbamazepine, phenobarbital, phenytoin	Strong CYP3A4 inducers are contraindicated
Antihyperlipidemics	Gemfibrozil	Strong CYP2C8 inhibitors are contraindicated
	Lovastatin, simvastatin	Contraindicated due to risk of myopathy
Antimycobacterials	Rifampin	Strong CYP3A4 inducers contraindicated
Antipsychotics	Pimozide	Contraindicated due to risk of QT prolongation
Antiretrovirals	Darunavir/ritonavir	Not recommended due to decreased darunavir concentrations
	Efavirenz	Contraindicated due to liver enzyme elevations
	Lopinavir/ritonavir	Not recommended due to increased paritaprevir concentrations
	Rilpivirine	Not recommended due to risk of QT prolongation
Anxiolytics	Oral midazolam, triazolam	Contraindicated due to increased risk of serious side effects including sedation and respiratory depression
Ergot derivatives	Ergotamine, dihydroergotamine, ergonovine, methylergonovine	Contraindicated due to risk of ergot toxicity
Herbal products	St John’s wort	Strong CYP3A4 inducers contraindicated
Long-acting beta-adrenergic agonists	Salmeterol	Contraindicated due to risk of cardiovascular adverse effects such as QT prolongation
Oral contraceptives	Ethinyl estradiol-containing products	Contraindicated due to liver enzyme elevations
Phosphodiesterase-5 inhibitors	Sildenafil (for treatment of pulmonary arterial hypertension)	Contraindicated due to increased risk of sildenafil-associated adverse effects
Dose adjustments recommended
Angiotensin II receptor blockers	Valsartan, olmesartan, telmisartan	Increased concentrations of OATP1B substrates; lower doses recommended
Antifungals	Ketoconazole	Increased concentrations of CYP3A substrates; limit ketoconazole and itraconazole to ≤200 mg/day
		Lower doses for posaconazole
		Voriconazole not recommended
Antihyperlipidemics	Pravastatin, rosuvastatin	Increased concentrations of OATPB1 substrates
		Maximum dose pravastatin 40 mg/day
		Maximum dose rosuvastatin 10 mg/day
		Lower doses of pitavastatin and fluvastatin
Antiretrovirals	Atazanavir/ritonavir	Administer atazanavir (without ritonavir) in the morning
Calcium channel blockers	Amlodipine	Increased concentrations of CYP3A4 substrates
		Reduce amlodipine by 50%
		Lower doses for other calcium channel blockers and monitor
		Avoid felodipine and nisoldipine
Immunosuppressants	Cyclosporine	Reduce cyclosporine dose to 20% of current dose
		Subsequent dose modifications based on blood concentrations
		Monitor renal function and side effects frequently
	Tacrolimus	Do not administer tacrolimus on day of PrOD initiation
		Reduce tacrolimus based on blood concentrations
		Typical dose is 0.5 mg every 7 days
		Monitor renal function and side effects frequently
Caution warranted, therapeutic monitoring recommended
Antiarrhythmics	Amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine	Increased concentrations of antiarrhythmics
		Therapeutic concentration monitoring recommended
Antiretrovirals	Atazanavir/ritonavir	Administer atazanavir (without ritonavir) in the morning
Anxiolytics	Alprazolam	Consider a decrease in alprazolam dose based on clinical response
Corticosteroids (inhaled/nasal)	Fluticasone	Reduced concentrations of cortisol
		Consider alternative corticosteroids
Diuretics	Furosemide	Increased concentrations of furosemide
		Adjust dose based on patient response
Proton-pump inhibitors	Omeprazole	Consider omeprazole dose increase if symptoms are uncontrolled and avoid >40 mg/day of omeprazole
No clinically significant interactions
Antiaddictives	Buprenorphine, methadone, naloxone	No dose adjustments are required
Antiarrhythmics	Digoxin
Anticoagulants	Warfarin
Antidepressants	Escitalopram, citalopram, duloxetine, fluoxetine, paroxetine, desipramine
Antiretrovirals	Emtricitabine/tenofovir disoproxil fumarate, raltegravir
Oral contraceptives	Norethindrone-only products
Sleep aids	Zolpidem

Notes: Information adapted from previously published tables with permission from the publisher. This article was published in J Hepatol, 63(1), Menon RM, et al., Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir, 20–29.²⁹ Copyright ©2015 Elsevier.

Abbreviation: PrOD, paritaprevir/ritonavir/ombitasvir with dasabuvir.

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