Victim Drug (Dose) | Inhibitor (Dose) | Enzymes/ Transporters Possibly Involved | Max AUC Ratio | Max Cmax Ratio | Study Design/Populationb | 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 | Nc | 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 Cmax 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.