EFAVIRENZ

• Cytochrome P450 enzyme substrate: CP3A4 and CYP2B6
• Action to be taken: Caution and close monitoring
• Rationale: Sorafenib inhibits CYP2B6 in vitro. Co-administration with efavirenz is expected to increase systemic exposure of efavirenz, and caution is recommended.

NEVIRAPINE

• Cytochrome P450 enzyme substrate: CYP3A and CYP2B6
• Action to be taken: Caution and close monitoring
• Rationale: Telithromycin is a potent inhibitor of CYP3A4. Nevirapine plasma concentrations and HIV status are to be closely monitored.

RILPIVIRINE

• Cytochrome P450 enzyme substrate: CYP3A
• Action to be taken: Caution and close monitoring
• Rationale: Isoniazid is an inhibitor of CYP3A4.Close clinical monitoring is advised when administering with rilpivirine due to increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Co-administration may lead to increased rilpivirine plasma concentrations.

ETRAVIRINE

• Cytochrome P450 enzyme substrate: CYP3A4, CYP2C9, and CYP2C19
• Action to be taken: Caution with close monitoring
• Rationale: Fluconazole is a potent inhibitor of CYP2C9 and posaconazole is a potent inhibitor of CYP3A4. Careful monitoring is recommended when administered with posaconazole. With concomitant use with fluconazole, etravirine Cmax is increased by 75%, AUC by 86%, and Cmin by 109%. Safety data for increased etravirine serum concentrations is limited, however, the manufacturer of etravirine does not recommend a dose change when co-administered with other inhibitors.

References

1. Nexavar® (sorafenib) package insert. Emeryville, CA; Onyx Pharmaceuticals Inc.,; 2007 Nov.
   
2. Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2016 Mar.
3. Ketek™ (telithromycin) package insert. Kansas City, MO: Aventis Pharmaceuticals; 2005 Feb.
4. Viramune® (nevirapine) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2008 Jun.
5. Wen X, Wang JS, Neuvonen PJ, et al. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol 2002;57:799-804.
6. Desta Z, Soukhova NV, Flockhart DA. Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother 2001;45:382-92.
7. Edurant (rilpivirine) package insert. Titusville, NJ: Janssen Therapeutics; 2015 Aug
8. Intelence (etravirine) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2014 Aug.