Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
Status:
Unknown status
Trial end date:
2011-07-01
Target enrollment:
Participant gender:
Summary
There are increasing numbers of HIV-infected patients in sub-Saharan Africa receiving
antiretroviral drugs and/or rifampicin based antituberculous therapy. HIV infected patients
are at an increased risk of contracting malaria. Increasing resistance to anti-malarials such
as chloroquine, amodiaquine, fansidar, sulphadoxine-pyrimethamine in East and West Africa has
led the WHO to recommend artemether-lumefantrine (Coartem®- Novartis) as first line therapy
for malaria for adults and children. As early as 2004, fourteen countries in sub-Saharan
Africa had adopted this guideline as national policy.
There are no data on the interaction between Coartem® and any of the antiretroviral agents.
Both components of Coartem® are substrates for the 3A4 isoform of cytochrome P450. Despite
the lack of data, antiretroviral drugs and/or antituberculous drugs in addition to Coartem®
are of necessity co-prescribed daily in the African setting. Nevirapine, efavirenz and
rifampicin are known inducers of cytochrome P450 3A4. A technical consultation convened by
WHO in June, 2004 concluded that additional research on interactions between antiretroviral
and antimalarial drugs is urgently needed.
We propose to perform a suite of pharmacokinetic studies to evaluate these interactions in
HIV infected Ugandan patients. The aim of these studies is to evaluate the pharmacokinetic
interaction between Coartem® and commonly co-prescribed inducers of 3A4 i.e. nevirapine,
efavirenz and rifampicin.
1. Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior
to commencement of nevirapine and at nevirapine steady state
2. Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior
to commencement of efavirenz and at efavirenz steady state
3. Comparison of steady state pharmacokinetics of Coartem® in Ugandan patients at
rifampicin steady state and without rifampicin