Antimalarial levels sharply lower with rifampin in HIV+ in Uganda
Concentrations of the antimalaria drugs artemether and lumefantrine were sharply lower during rifampin-based anti-TB therapy in Ugandan adults with HIV. The researchers recommend avoiding simultaneous use of artemether-lumefantrine and rifampin.
Rifampin induces CYP3A4 and CYP2C9 liver enzymes and so can affect levels of drugs that use those enzymes for metabolism. Tuberculosis or malaria—and sometimes both—occur in HIV-positive people in regions with high prevalence of these diseases. Treating two infections at the same time can be complicated because of drug interactions and toxicities; treating three infections simultaneously is even more difficult.
This open-label, two-phase drug interaction study involved 6 HIV-positive Ugandan adults receiving rifampin-based anti-TB therapy who did not have malaria. They took artemether-lumefantrine for 3 weeks while continuing rifampin. Blood samples for drug level monitoring were collected during rifampin treatment (phase 1) and at least 3 weeks after people stopped rifampin (phase 2).
Six people completed study phase 1 and 5 completed phase 2. The study group had a median age of 30 years and a median weight of 64 kg.
Artemether 12-hour area under the concentration-time curve (AUC) was 89% lower during than after rifampin therapy (geometric mean ratio [GMR] 0.11, 90% confidence interval [CI] 0.05 to 0.26); 12-hour AUC of dihydroartemisinin (a metabolite of artemether) was 85% lower with rifampin (GMR 0.15, 95% CI 0.10 to 0.23).
Artemether and dihydroartemisinin maximum concentrations were 83% lower (GMR 0.17, 90% CI 0.08 to 0.39) and 78% lower (GMR 0.22, 90% CI 0.15 to 0.33) during than after rifampin therapy. Mean 12-hour concentrations of artemether were 0.5 (±1.0) ng/mL and 5.9 (±2.5) ng/mL during study phases 1 and 2. Mean dihydroartemisinin 12-hour concentrations were 0.3 (±0.4) ng/mL and 4.7 (±2.0) ng/mL in phases 1 and 2.
Compared with concentrations after stopping rifampin, day 8 lumefantrine concentration during rifampin therapy was significantly lower by 84% (GMR 0.16, 90% CI 0.09 to 0.27), and AUCDay3-Day25 was significantly lower by 68% (GMR 0.32, 90% CI 0.21 to 0.49).
The researchers conclude that “pharmacokinetic parameters for artemether-lumefantrine were markedly lower during rifampicin-based tuberculosis treatment,” so the antimalarials should not be given with rifampin.
Source: Mohammed Lamorde, Pauline Byakika-Kibwika, Jonathan Mayito, Lillian Nabukeera, Mairin Ryan, Warune Hanpithakpong, Gilbert Lefèvre, David J. Back, Saye H. Khoo, Concepta Merry. Lower artemether, dihydroartemisinin and lumefantrine concentrations during rifampicin-based tuberculosis treatment. AIDS. 2013; 27: 961-965.
For the study abstract
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Source: IAS
