Drug Interactions between artemether / lumefantrine and chloroquine

GENERALLY AVOID: Artemether-lumefantrine may cause prolongation of the QT interval. Theoretically, coadministration with other antimalarial agents that can prolong the QT interval (e.g., quinine, quinidine, halofantrine, chloroquine) may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials, asymptomatic prolongation of the Fridericia-corrected QT interval (QTcF) by more than 30 msec from baseline was reported in approximately one-third of patients treated with artemether-lumefantrine, and prolongation by more than 60 msec was reported in more than 5% of patients. A few patients (0.4%) in the adult/adolescent population and no patient in the infant/children population experienced a QTcF greater than 500 msec. However, the possibility that these increases were disease-related cannot be ruled out. A parallel three-group study conducted in 42 healthy male volunteers reported no significant pharmacokinetic interaction when quinine (10 mg/kg, up to 600 mg, intravenously over 2 hours) was given sequentially 2 hours after the last (sixth) dose of artemether-lumefantrine (80 mg-480 mg). Although plasma concentrations of artemether and its active metabolite dihydroartemisinin (DHA) appeared to be lower, these changes were not considered clinically relevant. In this study, administration of artemether-lumefantrine to 14 subjects had no effect on the QTc interval, whereas infusion of quinine alone in another 14 subjects caused a transient prolongation of the QTc interval. This effect was slightly, but significantly, greater (approximate increases of 7 and 15 msec in average and peak QTc interval, respectively) when quinine was infused after artemether-lumefantrine in an additional 14 subjects. Two subjects in this group also experienced a QTc interval greater than 450 msec. These results suggest that the inherent risk of QTc prolongation associated with intravenous quinine may be enhanced by prior administration of artemether-lumefantrine.

MANAGEMENT: Coadministration of artemether-lumefantrine with other drugs that can prolong the QT interval should be avoided. Moreover, artemether-lumefantrine should generally not be used in combination with other antimalarial agents due to limited safety data. Caution and close monitoring of the ECG are advised when QT-prolonging antimalarial agents are used following treatment with artemether-lumefantrine because of the long elimination half-life of lumefantrine (3 to 6 days). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

GENERALLY AVOID: Artemether-lumefantrine may cause prolongation of the QT interval. Theoretically, coadministration with other antimalarial agents that can prolong the QT interval (e.g., quinine, quinidine, halofantrine, chloroquine) may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials, asymptomatic prolongation of the Fridericia-corrected QT interval (QTcF) by more than 30 msec from baseline was reported in approximately one-third of patients treated with artemether-lumefantrine, and prolongation by more than 60 msec was reported in more than 5% of patients. A few patients (0.4%) in the adult/adolescent population and no patient in the infant/children population experienced a QTcF greater than 500 msec. However, the possibility that these increases were disease-related cannot be ruled out. A parallel three-group study conducted in 42 healthy male volunteers reported no significant pharmacokinetic interaction when quinine (10 mg/kg, up to 600 mg, intravenously over 2 hours) was given sequentially 2 hours after the last (sixth) dose of artemether-lumefantrine (80 mg-480 mg). Although plasma concentrations of artemether and its active metabolite dihydroartemisinin (DHA) appeared to be lower, these changes were not considered clinically relevant. In this study, administration of artemether-lumefantrine to 14 subjects had no effect on the QTc interval, whereas infusion of quinine alone in another 14 subjects caused a transient prolongation of the QTc interval. This effect was slightly, but significantly, greater (approximate increases of 7 and 15 msec in average and peak QTc interval, respectively) when quinine was infused after artemether-lumefantrine in an additional 14 subjects. Two subjects in this group also experienced a QTc interval greater than 450 msec. These results suggest that the inherent risk of QTc prolongation associated with intravenous quinine may be enhanced by prior administration of artemether-lumefantrine.

MANAGEMENT: Coadministration of artemether-lumefantrine with other drugs that can prolong the QT interval should be avoided. Moreover, artemether-lumefantrine should generally not be used in combination with other antimalarial agents due to limited safety data. Caution and close monitoring of the ECG are advised when QT-prolonging antimalarial agents are used following treatment with artemether-lumefantrine because of the long elimination half-life of lumefantrine (3 to 6 days). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.