indication

Lumefantrine and artemether combination therapy is indicated for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum, including malaria acquired in chloroquine-resistant areas. May also be used to treat uncomplicated malaria when the Plasmodium species has not been identified. Indicated for use in adults and children greater than 5 kg.

pharmacology

Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of β-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

toxicity

Common side effects of combination artemether/lumefantrine therapy in adults include headache, anorexia, dizziness, and asthenia. Common side effects in children include pyrexia, cough, vomiting, anorexia, and headache. Possible serious adverse effects include QT prolongation, bullous eruption, urticaria, splenomegaly (9%), hepatomegaly (adults, 9%; children, 6%), hypersensitivty reaction, and angioedema.

biotransformation

Extensively metabolized in the liver primarily by cytochrome P450 3A4. The major metabolite found in plasma is desbutyl-lumefantrine.

absorption

Food increases absorption.

half life

~ 4.5 days

drug interactions

Amiodarone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Amitriptyline: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Amoxapine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Apomorphine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Arsenic trioxide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Azithromycin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Bepridil: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Chloroquine: Chloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Chlorpromazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Cisapride: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Citalopram: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Dapsone: Concomitant therapy may increase the risk of adverse hemolytic reactions. Monitor patients closely for symptoms of hemolytic reactions during concomitant therapy. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, methoglobulin reductase deficiency or hemoglobin M are at higher risk of experiencing hemolytic reactions.

Doxepin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Droperidol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Erythromycin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Escitalopram: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Flecainide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Fluconazole: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Fluoxetine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Flupenthixol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Foscarnet: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Gadobutrol: Additive QTc-prolongation may occur. Consider alternate therapy or monitor closely for QTc-prolongation.

Gadofosveset trisodium: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Halofantrine: Halofantrine may increase the adverse effects of lumefantrine. Additive QTc-prolongation may occur. Combination therapy is contraindicated and therapies should not be administered within one month of each other due to the long half-life of lumefantrine.

Haloperidol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Hydroxychloroquine: Hydroxychloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Ibutilide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Imipramine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Indapamide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Isradipine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Lapatinib: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Levofloxacin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Loxapine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Mefloquine: Mefloquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Mesoridazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Methadone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Methotrimeprazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Moxifloxacin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Nilotinib: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Norfloxacin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Nortriptyline: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Octreotide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Pentamidine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Perflutren: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Pimozide: Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.

Primaquine: Primaquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Probucol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Procainamide: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Proguanil: Proguanil may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Propafenone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Protriptyline: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Pyrimethamine: Pyrimethamine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Quetiapine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Quinidine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Quinine: Quinine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.

Ranolazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Risperidone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Sotalol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Sparfloxacin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Sunitinib: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Tacrolimus: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Tamoxifen: Lumefantrine, a moderate CYP2D6 inhibitor, may decrease the formation of highly potent tamoxifen metabolites. Concomitant therapy may decrease the effectiveness of tamoxifen. Consider alternate therapy.

Telithromycin: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Tetrabenazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Thioridazine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Thiothixene: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Toremifene: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Trimipramine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Voriconazole: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Vorinostat: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Ziprasidone: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.