Lumefantrine

Identification

Summary

Lumefantrine is an antimalarial agent used in combination with artemether for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum.

Brand Names
Coartem
Generic Name
Lumefantrine
DrugBank Accession Number
DB06708
Background

Lumefantrine is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 528.94
Monoisotopic: 527.154947772
Chemical Formula
C30H32Cl3NO
Synonyms
  • (±)-2,7-Dichloro-9-((Z)-p-chlorobenzylidene)-α-((dibutylamino)methyl)fluorene-4-methanol
  • 2-Dibutylamino-1-[2,7-dichloro-9-(4-chloro-benzylidene)-9H-fluoren-4-yl]-ethanol
  • 2-Dibutylamino-1-{2,7-dichloro-9-[1-(4-chloro-phenyl)-meth-(Z)-ylidene]-9H-fluoren-4-yl}-ethanol
  • Benflumetol
  • dl-Benflumelol
  • Lumefantrine

Pharmacology

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
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

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.

Absorption

Food increases absorption.

Volume of distribution

Not Available

Protein binding

99.7% bound

Metabolism

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

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Route of elimination

Not Available

Half-life

~ 4.5 days

Clearance

Not Available

Adverse Effects
Adverseeffects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Lumefantrine can be increased when it is combined with Abametapir.
AbirateroneThe metabolism of Lumefantrine can be decreased when combined with Abiraterone.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Lumefantrine.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Lumefantrine.
AcetophenazineThe risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Acetophenazine.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Lumefantrine.
AdenosineThe risk or severity of QTc prolongation can be increased when Adenosine is combined with Lumefantrine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Lumefantrine.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Lumefantrine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Alimemazine.
Interactions
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Food Interactions
  • Avoid grapefruit products.
  • Take with food. Food increases absorption.

Products

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Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ARTEMETERO 20 MG + LUMEFANTRINA 120 MG TABLETALumefantrine (120 mg) + Artemether (20 mg)TabletOralMACLEODS PHARMACEUTICALS LTD2010-03-212021-10-01Colombia flag
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralCentral Texas Community Health Centers2009-04-07Not applicableUS flag
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralNovartis Pharmaceuticals Corporation2009-04-07Not applicableUS flag00078 0568 45 nlmimage10 6c443641
CoartemLumefantrine (120 mg/1) + Artemether (20 mg/1)TabletOralDepartment Of State Health Services, Pharmacy Branch2009-04-072018-02-28US flag
COARTEM 20/120Lumefantrine (120 mg) + Artemether (20 mg)Tablet, orally disintegratingOralบริษัท โนวาร์ตีส (ประเทศไทย) จำกัด2017-10-28Not applicableThailand flag
COARTEM DISPERSIBLE (20/120 MG TABLETS)Lumefantrine (120 MG) + Artemether (20 MG)Tablet, solubleOralบริษัท โนวาร์ตีส (ประเทศไทย) จำกัด2017-10-28Not applicableThailand flag
KOMEFAN 140Lumefantrine (120 mg) + Artemether (20 mg)TabletOralLABORATORIOS VIHCORP LTDA2015-09-14Not applicableColombia flag

Categories

ATC Codes
P01BF01 — Artemether and lumefantrine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as fluorenes. These are compounds containing a fluorene moiety, which consists of two benzene rings connected through either a cyclopentane, cyclopentene, or cyclopenta-1,3-diene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Fluorenes
Sub Class
Not Available
Direct Parent
Fluorenes
Alternative Parents
Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives / Aromatic alcohols
Substituents
1,2-aminoalcohol / Alcohol / Amine / Aralkylamine / Aromatic alcohol / Aromatic homopolycyclic compound / Aryl chloride / Aryl halide / Chlorobenzene / Fluorene
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tertiary amine, secondary alcohol, monochlorobenzenes, fluorenes (CHEBI:156095)
Affected organisms
  • Plasmodium

Chemical Identifiers

UNII
F38R0JR742
CAS number
82186-77-4
InChI Key
DYLGFOYVTXJFJP-MYYYXRDXSA-N
InChI
InChI=1S/C30H32Cl3NO/c1-3-5-13-34(14-6-4-2)19-29(35)28-18-23(33)17-27-25(15-20-7-9-21(31)10-8-20)26-16-22(32)11-12-24(26)30(27)28/h7-12,15-18,29,35H,3-6,13-14,19H2,1-2H3/b25-15-
IUPAC Name
2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl]ethan-1-ol
SMILES
CCCCN(CCCC)CC(O)C1=C2C(=CC(Cl)=C1)\C(=C/C1=CC=C(Cl)C=C1)C1=C2C=CC(Cl)=C1

References

General References
Not Available
Human Metabolome Database
HMDB0015653
KEGG Drug
D03821
PubChem Compound
6437380
PubChem Substance
99443260
ChemSpider
4941944
BindingDB
50238630
RxNav
847728
ChEBI
156095
ChEMBL
CHEMBL38827
PharmGKB
PA165111722
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lumefantrine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailablePlasmodium Infections1
4CompletedBasic ScienceDrug Drug Interaction (DDI)1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
4CompletedBasic SciencePlasmodium Falciparum Clinical Episode / Plasmodium Falciparum Infection / Plasmodium Vivax Clinical Episode / Plasmodium Vivax Infection1
4CompletedOtherPlasmodium Infections1
4CompletedPreventionAnemia / Plasmodium Infections1
4CompletedPreventionPlasmodium Falciparum1
4CompletedScreeningPlasmodium Falciparum, Malaria1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Malaria caused by Plasmodium falciparum1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Tablet, orally disintegratingOral
Tablet, solubleOral
Tablet, film coatedOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.09e-05 mg/mLALOGPS
logP8.34ALOGPS
logP9.19ChemAxon
logS-7.2ALOGPS
pKa (Strongest Acidic)14.1ChemAxon
pKa (Strongest Basic)9.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity160.81 m3·mol-1ChemAxon
Polarizability60.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9363
Caco-2 permeable+0.6319
P-glycoprotein substrateSubstrate0.8389
P-glycoprotein inhibitor IInhibitor0.6854
P-glycoprotein inhibitor IINon-inhibitor0.5475
Renal organic cation transporterInhibitor0.5792
CYP450 2C9 substrateNon-substrate0.7971
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7076
CYP450 1A2 substrateInhibitor0.6872
CYP450 2C9 inhibitorNon-inhibitor0.7112
CYP450 2D6 inhibitorInhibitor0.7727
CYP450 2C19 inhibitorNon-inhibitor0.6525
CYP450 3A4 inhibitorNon-inhibitor0.6983
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7168
Ames testNon AMES toxic0.6424
CarcinogenicityNon-carcinogens0.7629
BiodegradationNot ready biodegradable0.9924
Rat acute toxicity2.4077 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7654
hERG inhibition (predictor II)Inhibitor0.776
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: COARTEM (artemether and lumefantrine) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Lumefantrine inhibits CYP2D6 in vitro.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA Approved Drug Products: COARTEM (artemether and lumefantrine) tablets, for oral use [Link]

Drug created on May 16, 2010 01:04 / Updated on January 24, 2021 06:02