Coadministration has not been studied but could potentially decrease the levels of tamoxifen and metabolites via induction of CYP3A4 and thereby reduce the efficacy of tamoxifen. Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4. Coadministration of rifampicin, an inducer of cytochromes, markedly reduced tamoxifen and its metabolites concentrations and a similar effect may be expected with efavirenz. Tamoxifen has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on the metabolic profiles of both drugs there is little potential for pharmacokinetic interaction. Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. Endoxifen is formed from N-desmethyltamoxifen via CYP2D6 and from 4-hydroxytamoxifen via CYP3A4.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and clearance a clinically significant interaction with emtricitabine is unlikely. Coadministration of emtricitabine and efavirenz in the presence of didanosine was studied in 9 treatment naive, HIV+ patients. When compared to historical data for each drug alone, the pharmacokinetics of emtricitabine were not affected, didanosine AUC and Cmax were higher than expected and efavirenz Cmax, Cmin and AUC were lower than expected. However, efavirenz concentrations may have been underestimated as dosing was delayed by 12 hours for ease of sampling. Coadministration of tenofovir-DF and efavirenz decreased efavirenz AUC and Cmax both by 4%; tenofovir AUC decreased by 1% and Cmax increased by 7%. No dosage adjustment of efavirenz is necessary.