Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults

  • Byakika-Kibwika P
  • Lamorde M
  • Mayito J
 et al. 
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Abstract

OBJECTIVES: Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine.

METHODS: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.

RESULTS: Efavirenz significantly reduced artemether maximum concentration (C(max)) and plasma AUC (median 29 versus 12 ng/mL, P 
CONCLUSIONS: Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed.

Author-supplied keywords

  • Antimalarial
  • Antiretroviral
  • Drugs
  • Malaria

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Authors

  • Pauline Byakika-Kibwika

  • Mohammed Lamorde

  • Jonathan Mayito

  • Lillian Nabukeera

  • Rhoda Namakula

  • Harriet Mayanja-Kizza

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