Lumefantrine/Artemether

ACTs are currently recommended artemether-lume-fantrine, artesunate + amodiaquine, artesunate + mefloquine, artesunate + sulfadoxine-pyrimethamine [1, 5]. In areas with amodiaquine and sulfadoxine-pyrimethamine resistance exceeding 20%, i.e., SE Asia, artesunate + mefloquine or artemether-lumefantrine should be used [1,5]. 

Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C et al. Amodiaquine alone, amodiaquine-i-sulfadoxine-pyrimethamine, amodi-aquine-i-artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children a four-arm randomised effectiveness trial. Lancet 2005 365(9469) 1474-80. 

Three currently-used artemisinin based combination therapies (ACT) artesunate-mefloquine, artemether-lumefantrine and dihydroartemisinin-piperaquine, have been proven highly simple, safe and effective in the treatment of multidrug resistant P. falciparum malaria. 

Artemether-lumefantrine has been the unique GMP product (Coartem) among ACT drugs and has mostly been used in Africa but the absorption of lumefantrine is dependent on co-administration with fat may limit its effectiveness. For adults four tablets (1 tablet 20 mg artemether -p 120 mg lumefantrine) twice daily for 3 days is used. 

Omari AAA, Gamble C, Garner P. Artemether-lumefantrine (four-dose regimen) for treating un-comphcated falciparum malaria. Cochrane Database Syst Rev 2006. 

Artemether-lumefantrine (Coartem, Riamet) Coformulated first-line therapy in many African countries... 

FLECAINIDE ARTEMETHER/ LUMEFANTRINE Risk of arrhythmias Additive effect Avoid co-administration... 

SSRIs ANTIMALARIALS- ARTEMETHER/ LUMEFANTRINE This antimalarial may cause dose-related dangerous arrhythmias A substrate, mainly of CYP3A4, which may be inhibited by high doses of fluvoxamine and to a lesser degree by fluoxetine Manufacturers recommend avoidance of antidepressants... 

SNRIs ANTIMALARIALS - ARTEMETHER/ LUMEFANTRINE t artemether/lumefantrine levels with risk of toxicity, including arrhythmias Venlafaxine inhibits CYP3A4, which is partly responsible for the metabolism of artemether Avoid co-administration with venlafaxine and caution with duloxetine... 

Bakshi R, Hermehng-Fritz I, Gathmann 1, Alter E. An integrated assessment of the clinical safety of artemether-lumefantrine a new oral fixed-dose combination antimalar-ial drug. Trans R Soc Trop Med Hyg 2000 94(4) 419-24. 

Lefevre G, Carpenter P, Souppart C, Schmidli H, Martin JM, Lane A, Ward C, Amakye D. Interaction trial between artemether-lumefantrine (Riamet) and quinine in healthy subjects. J Chn Pharmacol 2002 42(10) 1147-58. 

In a clinical trial in patients with malaria, intake of a light meal within one hour of Iumefantrine increased the bioavailability by 48%, and intake of a normal meal increased absorption twofold, when compared with liquids alone. After 24 to 48 hours in this study, most patients were eating normally. Artemether/lumefantrine should be taken with food. However, patients with acute uncomplicated malaria are unlikely to tolerate food.The manufacturer notes that patients should be encouraged to take artemether/lumefantrine with food as soon as this can be tolerated. They say that patients who remain averse to food during treatment should be closely monitored since they may be at greater risk of recrudescence (reappearance of the disease after a period of inactivity). ... 

Riamet (Artemether/Lumefantrine) Novartis Pharmaceuticals UK Ltd UK Summary of product characteristics, December 2006... 

Bindschedler M, Lefevre G, Ezzet F, Schaeffer N, Meyer I, Thomsen MS. Cardiac effects of co-artemetiier (artemether/lumefantrine) and mefloquine given alone or in combination to healtiiy volunteers. EurJ Clin Pharmacol (2000) 56,375-81. 

In a study in patients with acute uncomplicated falciparum malaria 15 patients were given a single 300-mg dose of artemether, with a single 750-mg dose of mefloquine 24 hours later. The AUC of mefloquine in these patients was found to be 27% lower than the AUC of 7 patients receiving mefloquine alone. However, the addition of artemether improved the rate of parasite clearance, and cure rates were similar between the groups. For discussion of a study that found mefloquine pharmacokinetics did not appear to be altered when artemether/lumefantrine was given 12 hours after mefloquine treatment, see Co-artemether + Mefloquine , p.224. Note that co-artemether (artemether with lumefantrine) is one of the recommended treatment options in the WHO guidelines for the treatment of uncomplicated falciparum malaria. ... 

Artemisinin derivatives (artemisinin, artemether/lumefantrine - S% of patients had an asymptomatic prolongation of QTc intervals by greater than 30 milliseconds, with an actual QTc of greater than 450 milliseconds in males and greater than 470 milliseconds in females) Levofloxacin (rare case reports of torsade de pointes)... 

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