Etravirine + Artemether/Lumefantrine = Precautionary

Effect on Concentration

Etravirine
No change
Applies within class?
No
Artemether/Lumefantrine
Decrease
Applies within class?
No

Pharmacologic Effects

Etravirine
Effect
N/A
Applies within class?
No
Artemether/Lumefantrine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 17-Jul-2018

Summary

Sources

Etravirine versus Artemether/Lumefantrine ^

Study Design

In a single-center, randomized, two-way, two-period cross-over study, 16 healthy volunteers divided into two groups. One group (n=8) received treatment A followed by treatment B with a washout period of 4 weeks; the other group (n=8) received treatment B followed by treatment A with a washout period of 4 weeks. treatment A: artemether/lumefantrine 80/480 mg alone for 3 days (6 doses of 4 tablets [20/120 mg] at 0, 8, 24, 36, 48, and 60h) treatment B: etravirine (ETR) 200 mg twice a day for 21 days (Day 1 to 21) with artemether/lumefantrine 80/480 mg (6 doses of 4 tablets [20/120 mg] at 0, 8, 24, 36, 48, and 60h) on Day 8 to 11, then single dose of ETR 200mg in the morning on Day 22.

Study Results

Coadministration of ETR with artemether/lumefantrine decreased the maximum concentration (Cmax) and AUC of both artemether and active metabolite of artemether, dihydroartemisinin (DHA). Geometric mean ratios (GMRs; ETR + artemether/lumefantrine / artemether/lumefantrine) [90% CIs] of Cmax, AUC and Cmin for artemether were 0.72 [0.55,0.94], 0.62 [0.48,0.80] and 0.82 [0.67,1.01], respectively; GMRs for DHA (ETR + artemether/lumefantrine / artemether/lumefantrine) [90% CIs] of Cmax, AUC and Cmin were 0.84 [0.71,0.99], 0.85 [0.75,0.97] and 0.83 [0.71,0.97], respectively. ETR administration modestly decreased lumefantrine exposure; GMR for lumefantrine (ETR + artemether/lumefantrine / artemether/ lumefantrine) [90% CIs] AUC was 0.87 [0.77, 0.98]. Artemether/lumefantrine administration did not have a clinically important effect on ETR plasma concentrations and AUC; GMRs (ETR + artemether/lumefantrine / ETR) [90% CIs] of Cmax, AUC and Cmin for ETR were 1.11 [1.06,1.17], 1.10 [1.06, 1.15] and 1.08 [1.04,1.14], respectively.

Study Conclusions

Concomitant use of artemether/lumefantrine and ETR may decrease plasma concentrations and AUC of artemether, active metabolite of artemether (DHA), and lumefantrine. Since clinical significance is unknown whether the decreased artemether or dihydroartemisinin exposure results in decreased antimalarial efficacy, closely monitor antimalarial efficacy of artemether/lumefantrine. Dosage adjustment for ETR is not needed as concomitant use of these two drugs does not have a clinically important effect on ETR plasma concentration or AUC.

References

Demasi R, Van delft Y, Mohammed P. Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. Hiv Medicine. 2013; 7: 421-429.