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: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Makerere University
• Collaborator: Health Research Board, Ireland
• Treatments: Artemether; Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination; Artemisinins; Efavirenz; Lumefantrine; Nevirapine; Rifampin

Criteria

Inclusion Criteria:

• Age over eighteen years

• Ability to provide full written informed consent

• Confirmed diagnosis of HIV infection

Exclusion Criteria:

• Haemoglobin < 8g/dl

• Liver and renal function tests > 3 times the upper limit of normal

• Pregnancy

• Use of known inhibitors or inducers of cytochrome P450 or P-glycoprotein.

• Use of herbal medications (information will be obtained from patients' medication history through interview with the patient)

• Abnormal EKG ie QTc (Rate adjusted QT interval) >450ms (men) or >470ms (women)

• Intercurrent Illness including malaria

• Known hypersensitivity to artemisinin-derivatives, halofantrine or lumefantrine

• History of cardiac disease