Artemether & Lumefantrine
Artemether with Lumefantrine tablet, a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively, is an antimalarial agent. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. The exact mechanism by which lumefantrine, exerts its anti-malarial effect is not well defined. Available data suggest lumefantrine inhibits the formation of β-hematin by forming a complex with hemin. Both artemether and lumefantrine were shown to inhibit nucleic acid and protein synthesis.
Absorption: Food enhances the absorption of both artemether and lumefantrine. Artemether is absorbed with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with plasma concentrations about 6 to 8 hours after administration.
Distribution: Artemether and Lumefantrine are both highly bound to human serum proteins in vitro (95.4% and 99.7% respectively). Dihydroartemisinin is also bound to human serum proteins (47% to 76%).
Metabolism: The metabolism of artemether is catalyzed predominantly by CYP3A4/5. Dihydroartemisinin (DHA) is an active metabolite of artemether. The metabolism of artemether is also catalyzed to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. Lumefantrine is metabolized mainly by CYP3A4 to desbutyl-lumefantrine. The systemic exposure to the metabolite desbutyl-lumefantrine is less than 1% of the exposure to the parent compound.
Excretion: Artemether and ADH are cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated more slowly, with a terminal half-life of 3-6 days in healthy volunteers and in patients with falciparum malaria.
Artemether with Lumefantrine tablet is indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum including malaria acquired in areas where chloroquine resistance has been reported.
Hypersensitivity to artemether, lumefantrine or any ingredient in the formulation
Special precautions and warning
Avoid use in patients with known QT prolongation, those with hypokalemia or hypomagnesemia and those taking other drugs that prolongs the QT interval
Antimalarial should not be given concomitantly, unless there is no other treatment option, due to limited safety data. QT prolonging drugs, including quinine and quinidine, should be used cautiously following artemether with lumefantrine tablets.
Substrate inhibitors or inducers of CYP34A, including antiretroviral medications, should be used cautiously with artemether with Lumefantrine tablets due to a potential loss of efficacy of the concomitant drug or additive QT prolongation.
Pregnancy: Pregnancy category C. The efficacy of this tablet in the treatment of acute, uncomplicated malaria in pregnant women has not been established. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: It is not known whether artemether or Lumefantrine is excreted in human milk. Caution should be exercised when artemether with lumefantrine tablet administered to a nursing woman. Animal data suggest both artemether and lumefantrine are excreted into breast milk. The benefits of breastfeeding to mother and infant should be weighed against potential risk from infant exposure to Artemether and lumefantrine through breast milk.
Pediatric use: The safety and effectiveness of Artemether with lumefantrine tablet have been established for the treatment of acute, complicated malaria in children 2 months of age and older with a body weight of 5kg and greater.
Hepatic and renal impairment: No specific pharmacokinetic studies have been performed in patients with either hepatic or renal impairment. No dosing adjustment is necessary in patients with mild or moderate hepatic impairment and renal impairment.
Nervous system disorders: Headache, dizziness
Metabolism and nutrition disorders: anorexia
Gastrointestinal disorders: vomiting, abdominal pain, diarrhea, nausea
Psychiatric disorders: sleep disorder, insomnia
Skin and subcutaneous tissue disorders: pruritus, rash
Respiratory, thoracic and mediastinal disorders: cough
General disorders and administration site conditions: pyrexia, chills, asthenia, fatigue.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia
Hepatobiliary disorders: hepatomegaly
Blood and lymphatic system disorders: splenomegaly, anemia
Dosage and directions for use
Artemether/lumefantrine tablet should be administering orally with food. A 3-day treatment schedule with a total of 6 doses is recommended as below
|Weight||Age (in years)||Day 1 0 hrs 8 hrs after||Day 2 morning evening||Day 3 morning evening|
|5 to less than 15kg||< 3||1 tablet (am) 1 tablet (pm)||1 tablet (am) 1 tablet (pm)||1 tablet (am) 1 tablet (pm)|
|15 to less than 25kg||≥ 3-8||2 tablets (am) 2 tablets (pm)||2 tablets (am) 2 tablets (pm)||2 tablets (am) 2 tablets (pm)|
|Adults & children 25kg less than 35kg||≥ 9-14||3 tablets (am) 3 tablets (pm)||3 tablets (am) 3 tablets (pm)||3 tablets (am) 3 tablets (pm)|
|> 35kg||> 14||4 tablets (am) 4 tablets (pm)||4 tablets (am) 4 tablets (pm)||4 tablets (am) 4 tablets (pm)|
There is no information on overdoses of artemether/lumefantrine tablets higher than the doses recommended for treatment. In cases of suspected overdosage, symptomatic and supportive therapy, which would include ECG and blood electrolyte monitoring, should be given as appropriate.
CYP3A4 Inhibitors (Ketoconazole): use cautiously due to potential for QT prolongation
Mefloquine: if used immediately before treatment, monitor for decreased efficacy of artemether/lumefantrine tablet and encourage food consumption.
Hormonal contraceptives: it may reduce effectiveness may be reduced; use an additional method of birth control.
Anti-Retrovirals: Use cautiously due to potential for QT prolongation, loss of anti-viral efficacy, or loss of anti-malarial efficacy of artemether/lumefantrine tablet.
CYP2D6 Substrates: Monitor for adverse reactions and potential QT prolongation.