Table 2.
Predicted drug-drug interaction (DDI) potential of rifamycin antibiotics with therapeutics used to treat HIV, fungal, malarial parasitic infections and cancer in tuberculosis patients.
| Interacting drugs | Drug metabolizing enzymes induced during treatment | DDI pattern | ||
|---|---|---|---|---|
| Rifampin (RIF) | Rifabutin (RFB) | Rifapentine (RPT) | ||
| Antiretroviral Drugs (ARVs) | ||||
| ARV Category I: Integrase Strand Transfer Inhibitors (INSTIs) | ||||
| Dolutegravir | CYP3A4, UGT1A1 | CYP3A4, UGT1A1 | CYP3A4 | RPT < RIF < RFB |
| Bictegravir | CYP3A4, UGT1A1 | CYP3A4, UGT1A1 | CYP3A4 | RPT < RIF < RFB |
| Elvitegravir | CYP3A4, UGT1A1, UGT1A3 | CYP3A4, UGT1A1, UGT1A3 | CYP3A4 | RPT < RIF < RFB |
| Raltegravir | UGT1A1 | UGT1A1 | RPT < RIF < RFB | |
| ARV Category II: Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | ||||
| Efavirenz | CYP2A6, 2B6 | CYP2A6, 2B6, 2C19 | RPT < RIF < RFB | |
| Etravirine | CYP3A4, 2C9 | CYP3A4, 2C9, 2C19 | CYP3A4 | RPT < RIF < RFB |
| Nevirapine | CYP3A4, 2B6 | CYP3A4, 2B6 | CYP3A4 | RPT < RIF/RFB |
| Rilpivirine | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| ARV Category III: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||||
| Abacavir | UGT1A1 | UGT1A1 | RPT < RIF < RFB | |
| ARV Category IV: Protease Inhibitors (PIs) | ||||
| Atazanavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Darunavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Fosamprinavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Lopinavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Saquinavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Tipranavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| ARV Category IV: Entry Inhibitors (EIs) | ||||
| Maraviroc | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| ARV Category V: Pharmacokinetic enhancers (PK boosters) | ||||
| Cobicistat | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Ritonavir | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Antifungals | ||||
| Terbinafine | CYP2B6, 2C8, 2C9, 3A4, 3A5 | CYP2B6, 2C19, 2C8, 2C9, 3A4, 3A5 | CYP2C8, 3A4 | RPT < RIF < RFB |
| Voriconazole | CYP2C9,CYP3A5 | CYP2C9,CYP2C19,CYP3A5 | - | RPT < RIF < RFB |
| Antimalarials | ||||
| Quinine | CYP3A4 | CYP3A4 | CYP3A4 | RPT < RIF < RFB |
| Anticancer Drugs | ||||
| Beta-estradiol | CYP3A4, 3A5, 3A7 | CYP3A4, 3A5, 3A7 | CYP3A4, 3A7 | RPT < RIF < RFB |
| Cyclophosphamide | CYP2A6, 2B6, 2C8, 2C9, 3A4 | CYP2A6, 2B6, 2C19, 2C8, 2C9, 3A4 | CYP2C8, 3A4 | RPT < RIF & RFB |
| Docetaxel | CYP3A4, 3A5 | CYP3A4, 3A5 | CYP3A4 | RPT < RIF < RFB |
| Etoposide | CYP2C9, 3A4, 3A5 | CYP2C9, 3A4, 3A5 | CYP3A4 | RPT < RIF < RFB |
| Ifosfamide | CYP2A6, 2B6, 2C8, 2C9, 3A4 | CYP2A6, 2B6, 2C19, 2C8, 2C9, 3A4 | CYP2C8, 3A4 | RPT < RIF & RFB |
| Omeprazole | CYP2A6, 2C9, 3A4 | CYP2A6, 2C19, 2C9, 3A4 | CYP3A4 | RPT < RIF < RFB |
| Paclitaxel | CYP2B6, 2C8, 3A4, 3A5 | CYP2B6, 2C8, 3A4, 3A5 | CYP2C8, 3A4 | RPT < RIF & RFB |
| Tamoxifen | CYB5A, CYP2B6, 2C9, 3A4, 3A5; UGT2B15 | CYP5A, 2B6, 2C19, 2C9, 3A4, 3A5 | CYP3A4 | RPT < RIF & RFB |
| Thalidomide | CYP2C9, 3A5 | CYP3A5 | RPT < RIF < RFB | |
| Tretinoin | CYP2B6, 2C8, 2C9, 3A4, 3A5, 3A7 | CYP2B6, 2C8, 2C9, 3A4, 3A5, 3A7, RDH16, ALDH8A1 | CYP2C8, 2S1, 3A4,3A7 | ND |
Abbreviations: CYP, cytochrome P450; UGT, UDP glucuronosyl transferase; RDH16, Retinol dehydrogenase 16 and ALDH8A1, aldehyde dehydrogenase 8 family member A1 and ND, not determined.