Identification
- Summary
Artemether is an antimalarial agent used in combination with lumefantrine for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum.
- Brand Names
- Coartem
- Generic Name
- Artemether
- DrugBank Accession Number
- DB06697
- Background
Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine 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
Structure for Artemether (DB06697)
- Weight
- Average: 298.3746
Monoisotopic: 298.178023942 - Chemical Formula
- C16H26O5
- Synonyms
- (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane
- 10-methoxy-1,5,9-trimethyl-(1R,4S,5R,8S,9R,10S,12R,13R)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
- Artemetero
- Artemether
- Artemetherum
- Artemisininelactol methyl ether
- Dihydroartemisinin methyl ether
- Dihydroqinghaosu methyl ether
- methyl-dihydroartemisinine
- β-artemether
- β-dihydroartemisinin methyl ether
- External IDs
- SM 224
- SM-224
Pharmacology
- Indication
Artemether and lumefantrine 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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Plasmodium infections •••••••••••• ••••••••• Used in combination to treat Acute, uncomplicated malaria caused by plasmodium falciparum Combination Product in combination with: Lumefantrine (DB06708) •••••••••••• - Contraindications & Blackbox Warnings
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In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of P. falciparum by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides 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
Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species.
The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals.
- Absorption
Food increases absorption.
- Volume of distribution
Not Available
- Protein binding
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
Rapidly metablized to its active metabolite, dihydroartemisinin.
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Artemether, 1.6 +/- 0.7 and 2.2 +/- 1.9 hr; Dihydroartemisinin, 1.6 +/- 0.6 and 2.2 +/- 1.5 hr
- Clearance
Not Available
- Adverse Effects
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Animal studies on acute toxicity show that the LD50 of Artemether in mice is a single i.g. administration of 895mg/kg and a single i.m. injection of 296mg/kg dose; in rats, the LD50 is a single i.m. injection of 597mg/kg dose.
- Pathways
Pathway Category Artemether Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Artemether can be increased when it is combined with Abametapir. Abatacept The metabolism of Artemether can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Artemether. Acalabrutinib The metabolism of Artemether can be decreased when combined with Acalabrutinib. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Artemether. - Food Interactions
- Avoid grapefruit products.
- Take with food. Food increases absorption.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Coartem Artemether (20 mg/1) + Lumefantrine (120 mg/1) Tablet Oral Department Of State Health Services, Pharmacy Branch 2009-04-07 2018-02-28 US 
Coartem Artemether (20 mg/1) + Lumefantrine (120 mg/1) Tablet Oral Central Texas Community Health Centers 2009-04-07 Not applicable US Coartem Artemether (20 mg/1) + Lumefantrine (120 mg/1) Tablet Oral Novartis Pharmaceuticals Corporation 2009-04-07 Not applicable US 
COARTEM 20/120 Artemether (20 mg) + Lumefantrine (120 mg) Tablet, orally disintegrating Oral บริษัท โนวาร์ตีส (ประเทศไทย) จำกัด 2017-10-28 Not applicable Thailand 
COARTEM DISPERSIBLE (20/120 MG TABLETS) Artemether (20 MG) + Lumefantrine (120 MG) Tablet, soluble Oral บริษัท โนวาร์ตีส (ประเทศไทย) จำกัด 2017-10-28 Not applicable Thailand
Categories
- ATC Codes
- P01BF01 — Artemether and lumefantrine
- P01BF — Artemisinin and derivatives, combinations
- P01B — ANTIMALARIALS
- P01 — ANTIPROTOZOALS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- Drug Categories
- Anti-Infective Agents
- Antimalarials
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Artemisinin and derivatives
- Artemisinins
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (weak)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Free Radicals
- Highest Risk QTc-Prolonging Agents
- Peroxides
- QTc Prolonging Agents
- Reactive Oxygen Species
- Sesquiterpenes
- Terpenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as artemisinins. These are sesquiterpenoids originally isolated from the herb Artemisia annua. Their structure is based on artemisinin, a tetracyclic compound that contains a 1,2-dioxepane fused to an octahydrobenzopyran moiety. The internal peroxide bridge is believed to be a key to the mode of action of artemisinins.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Prenol lipids
- Sub Class
- Sesquiterpenoids
- Direct Parent
- Artemisinins
- Alternative Parents
- Oxepanes / Trioxanes / Oxanes / Dialkyl peroxides / Oxacyclic compounds / Acetals / Hydrocarbon derivatives
- Substituents
- 1,2,4-trioxane / Acetal / Aliphatic heteropolycyclic compound / Artemisinin skeleton / Dialkyl peroxide / Hydrocarbon derivative / Organic oxygen compound / Organoheterocyclic compound / Organooxygen compound / Oxacycle
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- semisynthetic derivative, sesquiterpenoid, artemisinin derivative, cyclic acetal, organic peroxide (CHEBI:195280)
- Affected organisms
- Plasmodium
Chemical Identifiers
- UNII
- C7D6T3H22J
- CAS number
- 71963-77-4
- InChI Key
- SXYIRMFQILZOAM-HVNFFKDJSA-N
- InChI
- InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1
- IUPAC Name
- (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane
- SMILES
- [H][C@@]12CC[C@@H](C)[C@]3([H])CC[C@@]4(C)OO[C@@]13[C@]([H])(O[C@H](OC)[C@@H]2C)O4
References
- Synthesis Reference
Haynes RK, Vonwiller SC: Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues. Trans R Soc Trop Med Hyg. 1994 Jun;88 Suppl 1:S23-6. Pubmed.
- General References
- Makanga M, Krudsood S: The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009 Oct 12;8 Suppl 1:S5. doi: 10.1186/1475-2875-8-S1-S5. [Article]
- Mutabingwa TK, Adam I: Use of artemether-lumefantrine to treat malaria during pregnancy: what do we know and need to know? Expert Rev Anti Infect Ther. 2013 Feb;11(2):125-35. doi: 10.1586/eri.12.169. [Article]
- Haynes RK, Vonwiller SC: Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues. Trans R Soc Trop Med Hyg. 1994 Jun;88 Suppl 1:S23-6. [Article]
- External Links
- Human Metabolome Database
- HMDB0015643
- KEGG Drug
- D02483
- PubChem Compound
- 68911
- PubChem Substance
- 99443251
- ChemSpider
- 62138
- BindingDB
- 50022886
- 18343
- ChEBI
- 195280
- ChEMBL
- CHEMBL566534
- ZINC
- ZINC000014263142
- PharmGKB
- PA165111698
- PDBe Ligand
- D8Z
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Artemether
- PDB Entries
- 6fgd
- FDA label
- Download (1.73 MB)
- MSDS
- Download (566 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Uncomplicated Malaria caused by Plasmodium falciparum 1 4 Completed Not Available Malaria 1 4 Completed Basic Science Drug Drug Interaction (DDI) 1 4 Completed Basic Science Plasmodium Falciparum Clinical Episode / Plasmodium Falciparum Infection / Plasmodium Vivax Clinical Episode / Plasmodium Vivax Infection 1 4 Completed Other Malaria 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Tablet Oral Tablet, orally disintegrating Oral Tablet, soluble Oral Tablet, film coated Oral Tablet Oral 20 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 86-90 Not Available water solubility Insoluble # http://www.rxlist.com/coartem-drug.htm logP 3.53 AVERY,MA ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.457 mg/mL ALOGPS logP 3.02 ALOGPS logP 3.48 Chemaxon logS -2.8 ALOGPS pKa (Strongest Basic) -3.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 46.15 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 74.66 m3·mol-1 Chemaxon Polarizability 32.12 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9012 Blood Brain Barrier + 0.9393 Caco-2 permeable + 0.7876 P-glycoprotein substrate Substrate 0.6031 P-glycoprotein inhibitor I Inhibitor 0.8918 P-glycoprotein inhibitor II Non-inhibitor 0.7056 Renal organic cation transporter Non-inhibitor 0.8178 CYP450 2C9 substrate Non-substrate 0.8665 CYP450 2D6 substrate Substrate 0.5341 CYP450 3A4 substrate Substrate 0.7023 CYP450 1A2 substrate Inhibitor 0.6829 CYP450 2C9 inhibitor Non-inhibitor 0.9413 CYP450 2D6 inhibitor Non-inhibitor 0.9474 CYP450 2C19 inhibitor Non-inhibitor 0.8733 CYP450 3A4 inhibitor Non-inhibitor 0.9434 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9672 Ames test Non AMES toxic 0.7285 Carcinogenicity Non-carcinogens 0.9179 Biodegradation Not ready biodegradable 0.9956 Rat acute toxicity 2.2114 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9502 hERG inhibition (predictor II) Non-inhibitor 0.7601
Spectra
- Mass Spec (NIST)
- Download (7.86 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 172.2723995 predictedDarkChem Lite v0.1.0 [M-H]- 172.3726995 predictedDarkChem Lite v0.1.0 [M-H]- 170.1053 predictedDeepCCS 1.0 (2019) [M+H]+ 173.2558995 predictedDarkChem Lite v0.1.0 [M+H]+ 172.8537995 predictedDarkChem Lite v0.1.0 [M+H]+ 172.0007 predictedDeepCCS 1.0 (2019) [M+Na]+ 172.2998995 predictedDarkChem Lite v0.1.0 [M+Na]+ 179.03966 predictedDeepCCS 1.0 (2019)
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- 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
- van Agtmael MA, Gupta V, van der Graaf CA, van Boxtel CJ: The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999 Oct;66(4):408-14. doi: 10.1053/cp.1999.v66.a101946. [Article]
- van Agtmael MA, Gupta V, van der Wosten TH, Rutten JP, van Boxtel CJ: Grapefruit juice increases the bioavailability of artemether. Eur J Clin Pharmacol. 1999 Jul;55(5):405-10. doi: 10.1007/s002280050648. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- 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 oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Mutagonda RF, Kamuhabwa AAR, Minzi OMS, Massawe SN, Asghar M, Homann MV, Farnert A, Aklillu E: Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267. doi: 10.1186/s12936-017-1914-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Elsherbiny DA, Asimus SA, Karlsson MO, Ashton M, Simonsson US: A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens. J Pharmacokinet Pharmacodyn. 2008 Apr;35(2):203-17. doi: 10.1007/s10928-008-9084-6. Epub 2008 Mar 19. [Article]
- Hedrich WD, Hassan HE, Wang H: Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425. doi: 10.1016/j.apsb.2016.07.016. Epub 2016 Aug 9. [Article]
- COARTEM® (artemether and lumefantrine) tablets, for oral use - FDA Label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Kakuda TN, DeMasi R, van Delft Y, Mohammed P: Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9. doi: 10.1111/hiv.12019. Epub 2013 Feb 26. [Article]
- COARTEM® (artemether and lumefantrine) tablets, for oral use - FDA Label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- Curator comments
- There is limited data confirming enzyme induction of CYP2C19 in the literature [A16806, F1516].
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Elsherbiny DA, Asimus SA, Karlsson MO, Ashton M, Simonsson US: A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens. J Pharmacokinet Pharmacodyn. 2008 Apr;35(2):203-17. doi: 10.1007/s10928-008-9084-6. Epub 2008 Mar 19. [Article]
- Giao PT, de Vries PJ: Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet. 2001;40(5):343-73. doi: 10.2165/00003088-200140050-00003. [Article]
- COARTEM® (artemether and lumefantrine) tablets, for oral use - FDA Label [Link]
Drug created at May 05, 2010 18:03 / Updated at February 21, 2021 18:52