TABLE 8

Clinically significant inhibition interactions, NMEs as victims or perpetrators

Victim Drug (Dose)	Inhibitor (Dose)	Enzymes/ Transporters Possibly Involved	Max AUC Ratio	Max C_max Ratio	Study Design/Population^{^b}	Labeling Impact	Reference
Tacrolimus (2 mg alone and 0.5 mg with perpetrators SD)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 28 d)	CYP3A, P-gp	57.07	16.48	One-sequence/12 healthy subjects	Y	FDA, 2014ai
Paritaprevir (300 mg SD)^{^a}	Ritonavir (100 mg SD)	CYP3A, OATP1B1	47.43	28.07	Parallel/6 healthy subjects per group	Y	FDA, 2014ai
Naloxegol (25 mg SD)^{^a}	Ketoconazole (400 mg once daily for 5 d)	CYP3A, P-gp	12.42	9.12	One-sequence/22 healthy subjects	Y	FDA, 2014t
Eliglustat (100 mg twice daily for 14–17 d)^{^a}	Paroxetine (30 mg once daily for 10 d)	CYP2D6	10.00	8.20	One-sequence/24 healthy subjects (CYP2D6 EMs)	Y	FDA, 2014e
Dasabuvir (400 mg SD)^{^a}	Gemfibrozil (600 mg twice daily for 5 d)	CYP2C8	9.90	1.91	One-sequence/11 healthy subjects	Y	FDA, 2014ai
Tasimelteon (5 mg SD)^{^a}	Fluvoxamine (50 mg once daily for 7 d)	CYP1A2 (3A, 2C9, 2C19)	6.87	2.28	One-sequence/24 healthy subjects	Y	FDA, 2014l
Pirfenidone (801 mg SD)^{^a}	Fluvoxamine (50–100 mg once daily or twice daily for 10 d)	CYP1A2	6.81 (smokers), 3.97 (nonsmokers)	2.24 (smokers), 1.69 (nonsmokers)	One-sequence/healthy subjects (26 smokers and 25 nonsmokers)	Y	FDA, 2014i
Cyclosporine (100 mg SD alone, 10 mg SD with inhibitors)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 21 d)	CYP3A, P-gp	5.80	15.73	One-sequence/12 healthy subjects	Y	FDA, 2014ai
Midazolam (5 mg SD)	Idelalisib (150 mg twice daily for 8 d)^{^a}	CYP3A	5.15	2.31	One-sequence/11 healthy subjects	Y	FDA, 2014an
Eliglustat (100 mg twice daily for 14 d)^{^a}	Ketoconazole (400 mg once daily for 7 d)	CYP3A	4.40	4.25	One-sequence/24 healthy subjects (CYP2D6 EMs)	Y	FDA, 2014e
Ceritinib (450 mg SD)^{^a}	Ketoconazole (200 mg twice daily for 14 d)	CYP3A	2.88	1.23	One-sequence/19 healthy subjects	Y	FDA, 2014ao
Simeprevir (150 mg once daily for 10 d)	Ledipasvir (30 mg once daily for 10 d)^{^a}	P-gp	2.84	2.56	Random Crossover/28 healthy subjects	Y	FDA, 2014k
Suvorexant (4 mg SD)^{^a}	Ketoconazole (400 mg once daily for 11 d)	CYP3A	2.79	1.23	One-sequence/11 healthy males	Y	FDA, 2014c
Ritonavir (100 mg once daily for 28 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 250 mg twice daily for 14 d)	CYP3A, P-gp	2.78	2.54	One-sequence/12 healthy subjects	Y	FDA, 2014ai
Norgestimate (250 µg once daily for 21 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 250 mg twice daily for19 d)	CYP3A, UGT	Norelgestromin: 2.75; norgestrel: 2.64	Norelgestromin: 2.30; norgestrel: 2.46	One-sequence/3 healthy females	N^{^c}	FDA, 2014ai
Rosuvastatin (5 mg once daily for 21 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 14 d)	OATP1B1/3, BCRP	2.59	7.15	One-sequence/12 healthy subjects	Y	FDA, 2014ai
Rilpivirine (25 mg once daily for 28 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 14 d)	CYP3A	2.59	2.20	One-sequence/9 healthy subjects	Y	FDA, 2014ai
Olaparib (100 mg SD)^{^a}	Itraconazole (200 mg once daily for 8 d)	CYP3A	2.59	1.36	One-sequence/56 patients with advanced solid tumors	Y	FDA, 2014s
Amlodipine (5 mg SD)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 250 mg twice daily for 24 d)	CYP3A	2.57	1.26	One-sequence/14 healthy subjects	Y	FDA, 2014ai
Midazolam (7.5 mg SD)	Netupitant (300 mg SD)^{^a}	CYP3A	2.44	1.40	Random crossover/20 healthy subjects	Y	FDA, 2014a
Netupitant (300 mg SD)^{^a}	Ketoconazole (400 mg once daily for 12 d)	CYP3A	2.42	1.19	Random crossover/18 healthy subjects	Y	FDA, 2014a
Metoprolol (50 mg SD)	Eliglustat (150 mg twice daily for 5 d)^{^a}	CYP2D6	2.33	1.72	One-sequence/8 healthy subjects (CYP2D6 EMs)	Y	FDA, 2014e
Raltegravir (400 mg twice daily for 17 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 14 d)	UGT1A1	2.26	2.27	One-sequence/12 healthy subjects	N	FDA, 2014ai
Ketoconazole (400 mg once daily for 6 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir/ombitasvir 150/100/25 mg + dasabuvir 250 mg SD)	CYP3A	2.15	1.13	One-sequence/12 healthy subjects	Y	FDA, 2014ai
Buprenorphine (median 16 mg once daily for 25 d)	Ombitasvir,^{^a} paritaprevir,^{^a} dasabuvir,^{^a} and ritonavir (paritaprevir/ritonavir 150/100 once daily + ombitasvir 25 mg once daily + dasabuvir 400 mg twice daily for 14 d)	CYP3A	2.05	2.00	One-sequence/10 patients	Y	FDA, 2014ai
Ledipasvir (90 mg once daily for 10 d)^{^a}	Atazanavir/ritonavir (atazanavir/ritonavir 300/100 mg once daily for 10 d)	P-gp	2.05	1.93	Random crossover/30 healthy subjects	N	FDA, 2014k
Droxidopa (not provided)^{^a}	DOPA decarboxylase inhibitors (not specified)	Catechol-O-methyl transferase	2.00	NA	Not provided	Y	FDA, 2014w

Maximum AUC and C_max ratios of the victim drug are presented.
SD, single dose.
↵^a 2014 NMEs.
↵^b The number of subjects listed represents the number of subjects who completed the study, as described in the DIDB.
↵^c Although there is no labeling recommendation specific to norgestimate, ethinyl estradiol–containing oral contraceptives are contraindicated with Viekira Pak due to potential alanine aminotransferase elevation.