Inhibitors of CYP3A4 , TCADs, fecanide, metoprolol, protease inhibitors, grape friut juice, class I A and III antiarrhythmics, Drugs prolonging QT intervals, neuroleptics, azole antifungals, Antidepressants, macrolides, Fluroquinololnes, cisapride, other anti malarials

Headache, dizziness, Sleep disturbances, Palpitations, GI upset, anorexia, Pruritus, rash, Arthalgia, myalgia, Asthenia, fatigue, Cough, QT prolongation, Paraesthesia, Gait disturbances, Raised liver enzymes

Cardiac disease, history or family of sudden death, or QT elongation History of cardiac arrhyhmia,, Electrolyte imbalance Bradycardia, congestive heart failure with reduced LVEF Not tob used as prpophylaxis. Complicated malaria after plasmodium infections. Lactation

Special precautions- Severe cardiac , renal, or hepatic impairment, Monitor ECG,potassium, pregnancy

Each tablet containing Arthemether and Lumefantrine should be taken with high fat food or drink such as milk. twice for 3 concecutive days Based on patients weight dose is divided as follows- 5to 15 kg- 20mg +120mg > 15kg to 25kg- 40mg + 240mg > 25kg to 35kg - 60mg + 360mg > 35kg - 80mg + 480mg on 1st day two doses has to be given 8 hours apart and from 2nd day 12 hours apart.

Rationale for the Combination- According to the 2006 and 2010 WHO malaria treatment guidlines, uncomplicated falciparum malaria must be treated with ACT and not by Artemisinin alone or any other monotherapy Artemisinin when used correctly in combination with other antimalarial drugs is not only effective in treating malaria, but also prevents parasite developing drug resistence . Artemther is a fast acting Artemisinin drug with short half-life while Lumefanthine has a longer half-life. Artemether rapidly reduces parasite biomass and quiclky resolves clinical symptoms . Added to this .Lumefantrines longer duration of activity is thought to prevent recrudescence. This dual effect also appears to reduce the selective pressure on the parasite to develop resistence.

Pharmacokinetics

Both Arthemether and Lumefanthrine act as as blood scizontocides. The site of antiparasitic action of both components of the combination is the food vacuole of the malarial parasite, where they are thought to intefere with the conversion of heme, a toxic intermediate produced during hemoglobin breakdown to the non toxic hemozoin, malaria pigment. Parasites in the infected erythrocuytes ingest and degrade hemoglobin and concentrate iron in a vacuole in the form of toxic heme. normally heme is then made harmless by conversion into hemozin

Each tablet containing Arthemether and Lumefantrine should be taken with high fat food or drink such as milk, twice for 3 concecutive days

Artemether and Lumfantrine tablests are contrindicated during the first trimester of pregnancy. During the second and third trimeser treatment shpuld only be considered if the expected benefit to the mother outweighs the risk to the fetus.