IDI Groundbreaking Research Leads to Change in Product Label of Coartem®

A study conducted at the Infectious Diseases Institute (IDI) found that rifampicin – a key drug for treating tuberculosis – can dramatically reduce blood levels of the antimalarial drug, artemether-lumefantrine, commonly known as Coartem®.The findings of this study, which have been accepted by the manufacturer (Novartis) and the United States Food and Drug Administration, have led to a change in the product label for Coartem®.   In the revised label, the manufacturer indicates that Coartem® should not be used among patients receiving rifampicin. The work was part of the doctoral thesis of IDI scholar, Dr. Mohammed Lamorde. Funding for the study was obtained from the Health Research Board of Ireland through a grant (GHRA06/02) awarded to Academic Alliance member Dr. Concepta Merry.

Malaria and tuberculosis are major causes of illness and death in developing countries but there is inadequate information to guide simultaneous treatment for malaria among patients receiving treatment for tuberculosis. Artemether-lumefantrine is one of the most widely used drugs for treating malaria. When patients already receiving tuberculosis treatment with rifampicin were given a full course of artemether-lumefantrine tablets, artemether levels in blood were lower by 89% compared to levels that were seen in the same patients after stopping rifampicin treatment.  Furthermore, artemether is converted to another drug in the body called dihydroartemisinin (DHA) which is also active against malaria. However, DHA levels were also markedly lower by 85% during treatment with rifampicin-containing tuberculosis drugs. Lumefantrine levels in blood were lower by 68% during treatment with tuberculosis treatment containing rifampicin. The findings are important because previous studies suggest that low blood concentrations of artemether and lumefantrine may increase the risk of treatment failure for malaria. The main concern is that artemether-lumefantrine may not work as well among patients receiving rifampicin.

This is the first study investigating the effect of rifampicin on artemether-lumefantrine. The clinical study was conducted by IDI investigators with collaborators from Makerere University, Trinity College Dublin and University of Liverpool. The study enrolled seven patients without malaria. Blood levels of artemether, DHA and lumefantrine were measured at Mahidol University in Thailand. Training and logistics support was obtained from the INTERACT program. The study team members included Dr. Pauline Byakika-Kibwika, Dr. Lillian Nabukeera, Dr. Jonathan Mayito, Harriet Tibakabikoba, Jamila Nakku, Deborah Ekusai and Johnson Magoola.

As a result of this work, the European and Developing Countries Clinical Trials Partnership has awarded to Dr. Lamorde a Senior Fellowship grant (TA.2011.40200.047) to study the impact of rifampicin treatment on the blood levels of other drugs that are recommended for the treatment of malaria. Dr. Lamorde currently works within the IDI Research Department, heading the Clinical Trials Training Unit. He is also coordinating an interest group for health economics and outcomes research based at IDI.

Dr. Mohammed Lamorde specialises in Internal Medicine and Clinical Pharmacology, and is a Sewankambo Post-doctoral Research Fellow – The Sewankambo Clinical Scholar Programme was created in 2005, and is named in honor of founding Ugandan member of the Academic Alliance and Principal of the Makerere University College of Health Sciences, Professor Nelson Sewankambo.The Programme aims to train new, internationally recognized clinical investigators at Makerere University.