There are no significant changes in concentration of either Dolutegravir or Artemether-Lumefantrine. Standard doses of an antimalarial regimen containing Artemether-Lumefantrine can be used in patients receiving Dolutegravir 50mg once daily.
Dolutegravir vs Artemether/Lumefantrine
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Study Design
Healthy Ugandan volunteers were given standard clinical treatment doses of Artemether-Lumefantrine (AL) and 50mg of dolutegravir (DTG) once daily given with food. Rich PK sampling was performed after the final dose of AL. Two-way cross-over study design (n=16) with 1:1 randomization. Subjects received either 3 days of AL dosing or 6 days of DTG (to reach steady state) plus 3 days AL+DTG. Following washout (21 days), the opposite regimen was given. Clinical and laboratory adverse events (AE) were reported using DAIDS criteria. Artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DLF)were measured over 0-264 h (study A) using LC-MS. Noncompartmental analysis was performed (WinNonlin). Geometric mean ratios (GMR; 90% CI) for antimalarials +/- DTG for Cmax, Tmax and AUC to last measurable time point (AUClast) were computed.
Study Results
For ARM, GMR of Cmax without (N=7) and with DTG (N=7) was 0.87 (0.67-1.14), of Tmax was 1.06 (0.84-1.34) and of AUClast was 1.05 (0.84-1.32). For DHA, GMR of Cmax was 0.92 (0.79-1.07), for Tmax was 1.17 (0.92-1.49) and for AUClast was 0.92 (0.79-1.07). For LF, GMR of Cmax was 1.12 (0.97-1.29), for Tmax was 1.65 (1.02-2.69) and for AUClast was 1.10 (0.96-1.27). For DLF, GMR of Cmax was 0.96 (0.80-1.15), Tmax was 3.00 (2.06-4.36) and for AUClast was 0.96 (0.80-1.15).
Study Conclusions
Standard doses of the antimalarial combination Artemether/Lumefantrine can be used in patients receiving Dolutegravir 50mg once daily.
References
Walimba SI, Lamorde M, Waitt C. Dolutegravir interactions with artemether-lumefantrine and amodiaquine-artesunate. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. ; March 2018.
Dolutegravir vs Artemether/Lumefantrine
^
Study Design
Healthy Ugandan volunteers were given standard clinical treatment doses of Artemether-Lumefantrine (AL) and 50mg of dolutegravir (DTG) once daily given with food. Rich PK sampling was performed after the final dose of AL. Two-way cross-over study design (n=16) with 1:1 randomization. Subjects received either 3 days of AL dosing or 6 days of DTG (to reach steady state) plus 3 days AL+DTG. Following washout (21 days), the opposite regimen was given. Clinical and laboratory adverse events (AE) were reported using DAIDS criteria. Artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DLF)were measured over 0-264 h (study A) using LC-MS. Noncompartmental analysis was performed (WinNonlin). Geometric mean ratios (GMR; 90% CI) for antimalarials +/- DTG for Cmax, Tmax and AUC to last measurable time point (AUClast) were computed.
Study Results
For ARM, GMR of Cmax without (N=7) and with DTG (N=7) was 0.87 (0.67-1.14), of Tmax was 1.06 (0.84-1.34) and of AUClast was 1.05 (0.84-1.32). For DHA, GMR of Cmax was 0.92 (0.79-1.07), for Tmax was 1.17 (0.92-1.49) and for AUClast was 0.92 (0.79-1.07). For LF, GMR of Cmax was 1.12 (0.97-1.29), for Tmax was 1.65 (1.02-2.69) and for AUClast was 1.10 (0.96-1.27). For DLF, GMR of Cmax was 0.96 (0.80-1.15), Tmax was 3.00 (2.06-4.36) and for AUClast was 0.96 (0.80-1.15).
Study Conclusions
Standard doses of the antimalarials AL can be used in patients receiving DTG 50mg once daily.
References
Walimba SI, Lamorde M, Waitt C. Dolutegravir interactions with artemether-lumefantrine and amodiaquine-artesunate. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. ; March 2018.
Dolutegravir vs Artemether/Lumefantrine
^
Study Design
Healthy Ugandan volunteers were given standard clinical treatment doses of Artemether-Lumefantrine (AL) and 50mg of dolutegravir (DTG) once daily given with food. Rich PK sampling was performed after the final dose of AL. Two-way cross-over study design (n=16) with 1:1 randomization. Subjects received either 3 days of AL dosing or 6 days of DTG (to reach steady state) plus 3 days AL+DTG. Following washout (21 days), the opposite regimen was given. Clinical and laboratory adverse events (AE) were reported using DAIDS criteria. Artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DLF)were measured over 0-264 h (study A) using LC-MS. Noncompartmental analysis was performed (WinNonlin). Geometric mean ratios (GMR; 90% CI) for antimalarials +/- DTG for Cmax, Tmax and AUC to last measurable time point (AUClast) were computed.
Study Results
For ARM, GMR of Cmax without (N=7) and with DTG (N=7) was 0.87 (0.67-1.14), of Tmax was 1.06 (0.84-1.34) and of AUClast was 1.05 (0.84-1.32). For DHA, GMR of Cmax was 0.92 (0.79-1.07), for Tmax was 1.17 (0.92-1.49) and for AUClast was 0.92 (0.79-1.07). For LF, GMR of Cmax was 1.12 (0.97-1.29), for Tmax was 1.65 (1.02-2.69) and for AUClast was 1.10 (0.96-1.27). For DLF, GMR of Cmax was 0.96 (0.80-1.15), Tmax was 3.00 (2.06-4.36) and for AUClast was 0.96 (0.80-1.15).
Study Conclusions
Standard doses of the antimalarials AL can be used in patients receiving DTG 50mg once daily.
References
Walimbwa, SI, Larmode, M, Waitt, C, Kapoggoza, JP, Else, L, Amara, A. Dolutegravir interactions with artemether-lumefantrine and amodiaquine-artesunate. Conference On Retroviruses And Opportunistic Infections. Boston. ; March 2018.
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