What are the drug interactions with non-nucleoside reverse transcriptase inhibitors (NNRTIs) in antiretroviral therapy?

Updated: Jul 12, 2021
  • Author: Shahab Qureshi, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
  • Print
Answer

Answer

All non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized in the liver by CYP3A isoenzymes. Efavirenz (EFV) and nevirapine (NVP) are also substrates of CYP2B6 enzymes, and etravirine (ETR) is a substrate of CYP2C9 and CYP2C19 enzymes. Coadministration with drugs that induce or inhibit these enzymes can alter NNRTI drug concentrations, resulting in virologic failure or adverse effects. [3]

All NNRTIs (except rilpivirine [RPV]) induce or inhibit CYP isoenzymes. EFV acts as a mixed inducer and inhibitor, but, similarly to NVP, it primarily induces CYP3A and 2B6 enzymes. ETR also induces CYP3A but inhibits CYP2C9 and 2C19 enzymes.

Examples of medications that interact with NNRTIs include azole antifungals (ketoconazole, itraconazole), rifamycins (eg, rifabutin, rifampin), benzodiazepines (eg, midazolam, triazolam), HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin), and methadone.

For more information, see the NIH Guidelines for Drug Interactions between NNRTIs and Other Drugs.

Table 1. NNRTIs Drugs and Their Metabolic Pathways [3] (Open Table in a new window)

Generic (Brand)

Metabolized by (ie, Substrate of)

Induces

Inhibits

Doravirine (Pifeltro)

DOR

CYP3A4, 3A5

- -

Delavirdine (Rescriptor)

DLV

CYP3A4 (primarily)

CYP2D6 (possibly)

-

CYP3A4 (potent)

CYP2D6

CYP2C9

CY2C19

Efavirenz (Sustiva)

EFV

CYP2B6 (primarily)

CYP2A6

CYP3A4

CYP3A4 (stronger inducer than inhibitor)

CYP2B6

CYP3A4

CYP2C9

CYP2C19

Etravirine (Intelence)

ETR

CYP3A4

CYP2C9

CYP2C19

CYP3A4

P-gp

CYP2C9

CYP2C19

Nevirapine (Viramune, Viramune XR)

NVP

CYP3A4

CYP2B6

CYP3A4

CYP2B6

-

Rilpivirine

RPV

CYP3A4

-

-


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!