TABLE 9

Clinically significant inductions

DoseMain Enzyme/Transporter Possibly InvolvedRatioStudy Design/PopulationaLabeling ImpactReference
Victim DrugInducerAUCCmax
DDIs with AUC ratio ≤ 0.5b
 Isavuconazonium sulfatecRifampin (600 mg once daily)CYP3A0.030.25N/PContraindication with strong CYP3A4 inducersFDA (2015i)
 Flibanserin (100 mg SD)cRifampin (600 mg once daily for 9 days)CYP3A4, CYP2C19 (minor)0.040.10Random crossover/23 healthy femalesCYP3A4 inducers not recommendedFDA (2015a)
 Rolapitant (200 mg SD)cRifampin (600 mg once daily for 14 days)CYP3A40.120.68One-sequence/20 healthy subjectsAvoid CYP3A strong inducersFDA (2015za)
 Palbociclib (125 mg SD)cRifampin (600 mg once daily for 12 days)CYP3A0.150.28One-sequence/14 healthy subjectsAvoid moderate and strong CYP3A inducersFDA (2015n)
 Cobimetinib (60 mg SD)cRifampin (600 mg once daily)CYP3A4, P-gp0.17 (PBPK)0.37 (PBPK)PBPK modeling/simulations of healthy subjectsAvoid CYP3A strong inducersFDA (2015h)
 IvacaftorLumacaftorcCYP3A0.20N/PN/PCoadministration with strong CYP3A inducers is not recommendedFDA (2015u)
 Daclatasvir (60 mg SD)cRifampin (600 mg once daily for 9 days)CYP3A, CYP2C8 (minor), P-gp0.210.44One-sequence/14 healthy Asian MalesContraindication with strong CYP3A inducersFDA (2015j)
 Brexpiprazole (4 mg SD)cRifampin (600 mg once daily for 13 days)CYP3A40.240.69One-sequence/16 healthy subjectsIncrease dose with CYP3A strong inducersFDA (2015v)
 Ixazomib citrate (4 mg SD)cRifampin (600 mg once daily for 14 days)CYP3A0.260.46Parallel/16 patientsAvoid CYP3A strong inducersFDA (2015s)
 Cobimetinib (60 mg once daily for 21 days)cEfavirenz (600 mg once daily for 21 days)CYP3A4, P-gp0.27 (PBPK)0.29 (PBPK)PBPK modeling/simulations of healthy subjectsAvoid CYP3A moderate inducersFDA (2015h)
 Alectinib (600 mg SD)cRifampin (600 mg once daily for 13 days)CYP3A0.270.49One-sequence/24 healthy subjectsNoneFDA (2015b)
 Sonidegib (800 mg SD)cRifampin (600 mg once daily for 14 days)CYP3A0.280.46Parallel/16 healthy subjectsAvoid CYP3A strong inducersFDA (2015t)
 Sonidegib (200 mg once daily at steady state)cEfavirenz (600 mg once daily for 120 days)CYP3A0.31 (PBPK)0.4 (PBPK)PBPK modeling/simulations of patientsAvoid CYP3A moderate inducersFDA (2015t)
 Panobinostat (20 mg SD)cRifampin (600 mg once daily for 14 days)CYP3A, P-gp0.35 (PBPK)0.43 (PBPK)PBPK modeling/simulations of 10 trials of 10 healthy subjectsAvoid CYP3A strong inducersFDA (2015l)
 IvabradinecSt. John’s Wort extractCYP3A4, P-gp0.400.50N/PAvoid concomitant use of CYP3A4 inducersFDA (2015g)
DDIs with 0.8 < AUC ratio ≤ 0.5d
 Trabectedin (1.3 mg/m2 SD)c,eRifampin (600 mg once daily for 6 days)CYP3A4, P-gp0.550.77Random crossover/8 patientsAvoid CYP3A strong inducersFDA (2015zf)
 Amlodipine (5 mg once daily for 28 days)Lesinurad (400 mg once daily for 24 days)cCYP3A0.580.61One-sequence/13 healthy malesMonitor for a potential reduction in efficacy of sensitive CYP3A substratesFDA (2015zg)
 BupropionIsavuconazonium sulfate (200 mg once daily)cCYP2B60.580.69N/PCautionFDA (2015i)
 Edoxaban (60 mg SD)cRifampin (600 mg once daily for 7 days)P-gp0.601.00N/PAvoidFDA (2015w)
 Lesinurad (400 mg SD)cRifampin (600 mg once daily for 14 days)CYP2C90.620.76One-sequence/14 healthy malesMonitor for potential reduction in efficacy during concomitant use with moderate CYP2C9 inducerFDA (2015zg)
 Sildenafil (50 mg SD)Lesinurad and allopurinol (300 mg/200 mg once daily for 10 days)cCYP3A0.660.66Random crossover/12 healthy malesMonitor for a potential reduction in efficacy of sensitive CYP3A substratesFDA (2015zg)
 Daclatasvir (60 mg once daily for 14 days and 120 mg once daily for 5 days)cEfavirenz (600 mg once daily for 14 days)CYP3A, P-gp0.680.83One-sequence/17 healthy subjectsIncrease dose with CYP3A moderate inducersFDA (2015j)
 Ritonavir (100 mg twice daily)Isavuconazonium sulfatecCYP3A0.69Not providedN/PCautionFDA (2015i)
 Lopinavir (400 mg twice daily)Isavuconazonium sulfatecCYP3A0.73Not providedN/PCautionFDA (2015i)
 Flibanserin (100 mg SD) cEtravirine (200 mg twice daily for 15 days)CYP3A40.750.97One-sequence/24 healthy femalesCYP3A4 inducers not recommendedFDA (2015a)
  • N/P, not provided; SD, single dose.

  • a The number of subjects listed represents the number of subjects who completed both treatments, as described in the University of Washington Drug Interaction Database.

  • b For victim exposure.

  • c NMEs in 2015.

  • d For victim exposure with dose recommendation.

  • e Drug was given intravenously.