Drug interactions with etravirine (TMC-125)

Simon Collins, HIV i-Base

An overview of drug interactions with the investigational NNRTI etravirine (TMC-125) was presented by Thomas Kakuda. Etravirine is a substrate and inducer of CYP3A4 and a substrate and inhibitor of CYP2C, and has a different interaction profile compared to nevirapine and efavirenz.

Two-way PK interaction studies at steady-state were conducted with TMC125 and didanosine (ddI), tenofovir (TDF), the ritonavir (rtv)-boosted PIs darunavir (DRV), fosamprenavir (FPV) and tipranavir (TPV). The 1-way effect of omeprazole (OME) and ranitidine (RAN) on TMC125, and the 1-way effect of TMC125 on lopinavir (LPV) with saquinavir (SQV), methadone (MET) and sildenafil (SIL) were also studied.

Table 2: Summary of drug interaction studies with etravirine (TMC-125)

TMC-125 Recommendation
Fosamprenavir FPV increased by 69%. TMC-125 no change Consider dose reduction of FPV using TDM
Atazanavir TMC-125 Cmin, Cmax, AUC all increased by 50% (30% with ATV/r). ATZ Cmin reduced 47%, AUC by 17% (ATZ/r by 38% and 14%) Do not use unboosted ATZ. Use 300mg ATZ/100mg RTV
Sildenafil, N-desmethyl-SIL SIL reduced by 57%. N-sSIL reduced by 41%. No significant effect on TMC-125 Consider increasing dose of SIL
Tipranavir/r TMC-125 reduced by 75%.No significant effect on TPV Do not administer together
Darunavir/r TMC-125 reduced by 37%. No significant effect on DRV Not clinically relevant
Omeprazole TMC-125 increased by 41% Not clinically relevant

Results are summarised in Table 1. TMC-125 should not be coadministered with nevirapine, efavirenz, tipranavir/r, full dose ritonavir or unboosted PIs. Fosamprenavir and sildenafil may require dose adjustment. Coadministration with clarithromycin is not recommended for treatment of MAI. No significant effect on levels of either drug were seen with ddI, tenofovir, lopinavir/r, saquinavir/r, methadone, and oral contraceptives ethnylestradiol (exposure slightly increased) and norethindrone (similar PK with slighlly lower Cmin by 22%).


This overview highlight the complexity of drug interactions and the important of expert interpretation.

Effects on individual drugs need to be interpreted in the context of the pharmacokinetics of that compound – a 25% reduction for example may have clinical implications for one drug and not another.

Although both TMC-125 is relatively free of clinically important interactions, it is essential to be aware of the few contraindications with this new agent, and of the potential interactions that may require monitoring or dose modification.


Kakuda T, Schöller-Gyüre M, Woodfall B et al. TMC125 in combination with other medications: summary of drug-drug interaction studies. 8th International Congress on Drug Therapy in HIV Infection, 12-16 November 2006, Glasgow. Oral presentation PL5.2.

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