TABLE 8

Metabolism-based clinically significant inductions, NMEs as substrates or perpetrators

Victim Drug (Dose)Inducer (Dose)Enzyme(s) Possibly InvolvedMax AUC DecreaseStudy Design/PopulationReference (NDA#)
%
Ibrutiniba (dose not available)Rifampin (dose not available)CYP3A92.0bNot available(FDA, 2013j)
Macitentana (30 mg on day 1; 10 mg once daily 11 days)Rifampin (600 mg once daily 7 days)CYP3A79.0One-sequence/10 healthy subjects(Bruderer et al., 2012; FDA, 2013s)
Midazolam (3 mg SD)Dabrafeniba (150 mg twice daily repeated dosing)CYP3A74.1Not provided/12 patients(FDA, 2013w)
Simeprevira (150 mg once daily 14 days)Efavirenz (600 mg once daily 14 days)CYP3A70.6Random Crossover/23 healthy subjects(FDA, 2013r)
Dolutegravira (50 mg once daily 19 days)Etravirine (200 mg twice daily 14 days)UGT1A1, CYP3A70.5One-sequence/15 healthy subjects(FDA, 2013y)
Dabrafeniba (150 mg twice daily 21 days)Phenytoin (300 mg twice daily)CYP3A, CYP2C862.01 patient receiving dabrafenib with phenytoin (control data from 8 patients)(FDA, 2013w)
Ospemifenea (60 mg SD)Rifampin (600 mg once daily 5 days)CYP3A, CYP2C9, CYP2C1959.5Random Crossover/12 postmenopausal healthy women(FDA, 2013t)
Vortioxetinea (20 mg SD)Rifampin (600 mg once daily 11 days)CYP3A, Other P450s54.6One sequence/14 healthy subjects(Chen et al., 2013; FDA, 2013e)
Canagliflozina (300 mg SD)Rifampin (600 mg once daily 8 days)UGT (2B4/1A9)51.0Not provided/healthy subjects(FDA, 2013k)
Simvastatin (80 mg SD)Eslicarbazepine (acetate)a (800 mg once daily 14 days)CYP3A49.4Random Crossover/24 healthy subjects(Falcão et al., 2013; FDA, 2013c)
  • Maximum changes in the victim AUC are presented.

  • a 2013 NMEs are underlined.

  • b Preliminary data.