Coadministration of artemether/lumefantrine (80/480 mg twice daily) and efavirenz (600 mg once daily) decreased the AUC and Cmax of artemether by 51% and 21% and those of dihydroartemisinin by 46% and 38%. Lumefantrine AUC decreased by 21% but there was no change in Cmax. Efavirenz AUC decreased by 17%, with no change in Cmax. This was due to CYP3A4 induction. Since decreased concentrations of artemether, dihydroartemisinin, or lumefantrine may result in a decrease of antimalarial efficacy, caution is recommended when efavirenz and artemether/lumefantrine tablets are coadministered.
Sustiva Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, May 2023.

Coadministration of artemether/lumefantrine (80/480 mg twice daily) and efavirenz (600 mg once daily) was studied in 12 subjects. Coadministration decreased the Cmax and AUC of artemether by 21% and 51% and those of dihydroartemisinin by 38% and 46%. Lumefantrine AUC decreased by 21% but there was no change in Cmax. Efavirenz AUC decreased by 17%, with no change in Cmax. Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation.
Efavirenz US Prescribing Information, Aurobindo Pharma Limited, October 2021.

The pharmacokinetics of artemether, DHA, lumefantrine and efavirenz were determined in 12 HIV- negative and malaria-uninfected subjects who received artemether/lumefantrine (80/480 mg twice daily) for 3 days before and during efavirenz co-administration (600 mg daily for 26 days). The AUCs of artemether, DHA, and lumefantrine were lower with efavirenz, compared with when administered alone (decreases of 51%, 46% and 21% respectively). Day 7 lumefantrine levels, previously deemed predictive of treatment success, were 46% lower with efavirenz, but half-life was unchanged. Efavirenz AUC decreased by 17% after artemether/lumefantrine co-administration. The authors suggest that the observed modest changes probably do not warrant dosage adjustment during co-administration.Concomitant efavirenz reduces pharmacokinetic exposure to the antimalarial drug artemether-lumefantrine in healthy volunteers. Huang L, Parikh S, Rosenthal PJ, et al. J Acquir Immune Defic Syndr, 2012, 61(3): 310-6.

 

In a cross-over study, 30 HIV-infected adults received standard six-dose artemether/lumefantrine before and at efavirenz steady state.  Efavirenz significantly reduced artemether exposure by 79%, dihydroartemisinin exposure by 75% and lumefantrine exposure by 56%.  Lumefantrine did not affect efavirenz exposure. 
Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults. Byakika-Kibwika P, Lamorde M, Mayito J, et al.  J Antimicrob Chemother, 2012, 67(9): 2213-2221.