Artemether + Lumefantrine


Concise Prescribing Info
Indications/Uses
Acute uncomplicated falciparum malaria.
Dosage/Direction for Use
Adult : PO Each tab contains artemether 20 mg and lumefantrine 120 mg: ≥35 kg: Initial: 4 tab, followed by 4 tab given at 8, 24, 36, 48, and 60 hours thereafter to a total of 24 tab over 3 days.
Dosage Details
Oral
Acute uncomplicated falciparum malaria
Adult: Available preparation:
Artemether 20 mg and lumefantrine 120 mg

≥35 kg: Initially, 4 tab, followed by 4 tab given at 8, 24, 36, 48, and 60 hours thereafter to a total of 24 tab over 3 days.
Child: ≥2 months to ≤16 years 5-<15 kg: Initially 1 tab, followed by 1 tab given at 8, 24, 36, 48, and 60 hours thereafter; 15-<25 kg: Initially 2 tab, followed by 2 tab given at 8, 24, 36, 48, and 60 hours thereafter; 25-<35 kg: Initially 3 tab, followed by 3 tab given at 8, 24, 36, 48, and 60 hours thereafter. >16 years weighing ≥35 kg: Same as adult dose.
Administration
Should be taken with food.
Contraindications
Hypersensitivity, history of sudden death or congenital prolongation of QT interval, history of cardiac arrhythmias, bradycardia, CHF with reduced left ventricle ejection fraction, electrolyte disturbances (e.g. hypokalaemia, hypomagnesemia). Concomitant use with strong CYP3A4 inducers, and with drugs known to prolong QT interval.
Special Precautions
Severe renal and hepatic impairment. Children. Pregnancy and lactation. Not indicated for the prevention and treatment of severe or complicated malaria.
Adverse Reactions
Blood and lymphatic system disorders: Anaemia, splenomegaly.
Cardiac disorders: Palpitations, QT prolongation.
Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhoea.
General disorders and administration site conditions: Asthenia, fatigue, fever, malaise.
Hepatobiliary disorders: Hepatomegaly.
Infections and infestations: Malaria.
Investigations: Increased serum AST.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Arthralgia, chills, myalgia.
Nervous system disorders: Dizziness, headache, paraesthesia, clonus, gait disturbance vertigo.
Psychiatric disorders: Sleep disorder, insomnia.
Respiratory, thoracic and mediastinal disorders: Cough, rhinitis.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Potentially Fatal: Anaphylaxis.
Patient Counseling Information
This drug may cause dizziness, and fatigue, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor adequate food consumption during treatment.
Drug Interactions
May reduce effectiveness of hormonal contraceptives.
Potentially Fatal: Decreased plasma concentration with strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin). Additive QT prolongation effect with antiarrhythmics Class I and II (e.g. quinidine, amiodarone), antipsychotics (e.g. pimozide, ziprasidone), neuroleptics, antidepressants, antibiotics (e.g. macrolide, fluoroquinolone), triazole antifungals, non-sedating antihistamines (e.g. terfenadine, astemizole), cisapride, flecainide, halofrantine.
Food Interaction
Increased plasma level with grapefruit juice. Increased absorption with high fat meal. Decreased plasma concentration with St. John’s wort.
Action
Description: Artemether and lumefantrine exert their antimalarial action in the food vacuole of the parasite. They interfere with the conversion of haem (a toxic intermediate produced during haemoglobin breakdown) to the nontoxic haemozoin, malarial pigment. Both inhibit nucleic acid and protein synthesis.
Artemether and its active metabolite dihydroartemisinin (DHA) are rapid schizontocides. Its anti-malarial activity is attributed to their endoperoxide moiety.
Lumefantrine is a dichlorobenzylidine derivative. The exact mechanism of action of is still unknown, but it is thought to inhibit the formation of β-hematin by complexing with hemin.
Synonym: benflumentol.
Pharmacokinetics:
Absorption: Artemether: Rapidly absorbed from the gastrointestinal tract. Food, particularly high fat meal, increases absorption. Time to peak plasma concentration: Approx 2 hours.
Lumefantrine: Absorbed from the gastrointestinal tract after a lag-time of up to 2 hours. Food, particularly high fat meal, increases absorption. Time to peak plasma concentration: Approx 6-8 hours.
Distribution: Artemether: Plasma protein binding: Approx 95% (artemether); 47-76% (DHA).
Lumefantrine: Plasma protein binding: 99.7%.
Metabolism: Artemether: Metabolised in the liver by CYP3A4/5 enzymes via demethylation to its active metabolite, dihydroartemisinin (DHA) and to lesser extent by CYP2B6, C9, C19.
Lumefantrine: Metabolised in the liver by CYP3A4 enzyme to metabolite, desbutyl-lumefantrine.
Excretion: Artemether: Via urine (<0.01% as DHA). Elimination half-life: Approx 2 hours.
Lumefantrine: Via faeces as unchanged drug; urine (small amount). Elimination half-life: 3-6 days.
Chemical Structure

Chemical Structure Image
Artemether

Source: National Center for Biotechnology Information. PubChem Database. Artemether, CID=68911, https://pubchem.ncbi.nlm.nih.gov/compound/Artemether (accessed on Jan. 21, 2020)


Chemical Structure Image
Lumefantrine

Source: National Center for Biotechnology Information. PubChem Database. Lumefantrine, CID=6437380, https://pubchem.ncbi.nlm.nih.gov/compound/Lumefantrine (accessed on Jan. 21, 2020)

Storage
Store at 25°C.
MIMS Class
ATC Classification
P01BF01 - artemether and lumefantrine ; Belongs to the class of artemisinin and derivatives, combinations. Used in the management of malaria.
References
Anon. Artemether and Lumefantrine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/03/2018.

Buckingham R (ed). Artemether. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2018.

Buckingham R (ed). Lumefantrine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2018.

Coartem Tablets for Oral Use (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/03/2018.

Joint Formulary Committee. Artemether with Lumefantrine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/03/2018.

Disclaimer: This information is independently developed by MIMS based on Artemether + Lumefantrine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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