Table 1 A comparison of the final in vivo DDI guidance documents from NMPA, FDA, PMDA and EMA
NMPA | FDA | PMDA | EMA | |
|---|---|---|---|---|
Index substrates for CYP enzymes | ||||
CYP1A2 | Caffeine, Tizanidine | Caffeine, Tizanidine | Caffeine, Tizanidine | Caffeine |
CYP2B6 | - | - | - | Bupropion |
CYP2C8 | Repaglinide | Repaglinide | Repaglinide | Repaglinide |
CYP2C9 | S-warfarin*, Tolbutamide* | S-warfarin*, Tolbutamide* | S-warfarin, Tolbutamide | Flurbiprofen*, S-warfarin* |
CYP2C19 | Lansoprazole*, Omeprazole | Lansoprazole, Omeprazole, | Lansoprazole*, Omeprazole | Omeprazole |
CYP2D6 | Desipramine, Dextromethorphan, Metoprolol, Nebivolol | Desipramine, Dextromethorphan, Nebivolol | Desipramine, Dextromethorphan, Nebivolol | Desipramine, Dextromethorphan, Nebivolol |
CYP3A | Midazolam, Triazolam | Midazolam, Triazolam | Midazolam, Triazolam | Midazolam, Triazolam |
Index inhibitors for CYP enzymes | ||||
CYP1A2 | Enoxacin, Fluvoxamine, Ticlopidine | Fluvoxamine | Fluvoxamine | Fluvoxamine |
CYP2B6 | - | - | - | - |
CYP2C8 | Clopidogrel*, Gemfibrozil | Clopidogrel, Gemfibrozil | Clopidogrel, Gemfibrozil | Gemfibrozil |
CYP2C9 | Fluconazole* | Fluconazole* | Fluconazole* | Fluconazole* |
CYP2C19 | Fluconazole*, Fluvoxamine, Fluoxetine, Ticlopidine | Fluvoxamine | Fluvoxamine | Fluconazole, Fluvoxamine |
CYP2D6 | Fluoxetine, Paroxetine, Quinidine | Fluoxetine, Paroxetine | Fluoxetine, Mirabegron*, Paroxetine | Fluoxetine, Paroxetine |
CYP3A | Clarithromycin, Itraconazole, Ketoconazole, Ritonavir | Clarithromycin, Itraconazole | Clarithromycin, Erythromycin*, Fluconazole*, Itraconazole, Verapamil* | Clarithromycin, Itraconazole |
Inducers for CYP enzymes | ||||
CYP1A2 | Phenytoin*, Rifampicin | - | - | Phenytoin*, Rifampicin*, Smoking* |
CYP 2B6 | Carbamazepine, Rifampicin* | Rifampicin* | Rifampicin* | Carbamazepine, Efavirenz*, Rifampicin*, |
CYP2C8 | Rifampicin* | Rifampicin* | Rifampicin* | Rifampicin* |
CYP2C9 | Rifampicin* | Rifampicin* | Rifampicin* | Rifampicin* |
CYP2C19 | Rifampicin, Phenytoin* | Rifampicin | Rifampicin | Rifampicin |
CYP3A | Carbamazepine, Phenytoin, Rifampicin | Phenytoin, Rifampicin | Phenytoin, Rifampicin | Carbamazepine, Efavirenz*, Phenytoin, Rifampicin |