atovaquone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
258 95233-18-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • 566C80
  • atovaquone
  • mepron
A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.
  • Molecular weight: 366.84
  • Formula: C22H19ClO3
  • CLOGP: 6.35
  • LIPINSKI: 1
  • HAC: 3
  • HDO: 1
  • TPSA: 54.37
  • ALOGS: -5.66
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
2.25 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 3 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 58.41 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 23 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.15 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 63 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 25, 1992 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malaria 131.80 17.90 23 5294 219 46680526
Jaundice cholestatic 101.45 17.90 33 5284 4996 46675749
Hypomania 85.30 17.90 28 5289 4360 46676385
Schizophrenia 70.41 17.90 29 5288 8539 46672206
Hepatotoxicity 66.03 17.90 39 5278 24970 46655775
Psychotic disorder 61.62 17.90 36 5281 22585 46658160
Pyrexia 58.71 17.90 125 5192 348677 46332068
Cerebellar stroke 51.55 17.90 10 5307 177 46680568
Blood bilirubin increased 50.31 17.90 37 5280 34147 46646598
Congenital absence of cranial vault 45.31 17.90 7 5310 28 46680717
Pancytopenia 41.90 17.90 50 5267 85008 46595737
Neural tube defect 38.92 17.90 8 5309 192 46680553
Hepatocellular injury 36.91 17.90 29 5288 29493 46651252
Cell death 34.23 17.90 12 5305 2276 46678469
Cholelithiasis 32.02 17.90 30 5287 38651 46642094
Plasmodium falciparum infection 28.61 17.90 5 5312 48 46680697
Hepatic enzyme increased 27.70 17.90 40 5277 81747 46598998
Dermatitis acneiform 27.52 17.90 12 5305 4058 46676687
Thrombocytopenia 26.72 17.90 50 5267 126531 46554214
Systemic candida 25.04 17.90 10 5307 2717 46678028
Neutropenia 24.72 17.90 52 5265 143152 46537593
Diarrhoea 24.68 17.90 127 5190 559475 46121270
Toxic skin eruption 24.29 17.90 16 5301 12371 46668374
Cerebral toxoplasmosis 24.16 17.90 7 5310 719 46680026
Rash maculo-papular 23.80 17.90 22 5295 27852 46652893
Pneumocystis jirovecii pneumonia 23.54 17.90 17 5300 15231 46665514
Phyllodes tumour 23.12 17.90 4 5313 36 46680709
Cytokine release syndrome 22.67 17.90 12 5305 6211 46674534
Parasite blood test positive 22.16 17.90 3 5314 3 46680742
Lobular breast carcinoma in situ 21.30 17.90 4 5313 59 46680686
Dermatitis bullous 20.37 17.90 12 5305 7631 46673114
Eosinophilia 20.06 17.90 17 5300 19200 46661545
Agranulocytosis 19.89 17.90 18 5299 22167 46658578
Myeloid maturation arrest 19.42 17.90 3 5314 12 46680733
Hepatitis 19.33 17.90 21 5296 32194 46648551
Nocardiosis 18.65 17.90 7 5310 1610 46679135
Joint vibration 18.01 17.90 3 5314 21 46680724

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Nocardiosis 131.96 17.10 43 6463 3412 29942560
Malaria 117.06 17.10 23 6483 218 29945754
Immune reconstitution inflammatory syndrome 70.54 17.10 36 6470 9065 29936907
Pyrexia 70.20 17.10 179 6327 294310 29651662
Pancytopenia 50.22 17.10 76 6430 84976 29860996
Neutropenia 49.60 17.10 95 6411 128445 29817527
Thrombocytopenia 45.34 17.10 95 6411 136949 29809023
Toxoplasmosis 43.98 17.10 14 6492 1029 29944943
Drug reaction with eosinophilia and systemic symptoms 40.93 17.10 40 6466 28448 29917524
Hepatocellular injury 40.84 17.10 38 6468 25433 29920539
Pneumocystis jirovecii pneumonia 40.66 17.10 32 6474 17088 29928884
Plasmodium falciparum infection 40.40 17.10 7 6499 30 29945942
Mucormycosis 38.39 17.10 20 6486 5248 29940724
Cellulitis staphylococcal 30.98 17.10 10 6496 768 29945204
Febrile neutropenia 28.53 17.10 68 6438 106625 29839347
Parasite blood test positive 27.50 17.10 4 6502 3 29945969
Transaminases increased 23.16 17.10 27 6479 23430 29922542
Chylothorax 20.58 17.10 7 6499 633 29945339
Cholestasis 20.22 17.10 26 6480 24924 29921048
Gamma-glutamyltransferase increased 19.85 17.10 28 6478 29322 29916650
Alanine aminotransferase increased 19.46 17.10 47 6459 74229 29871743
Cutaneous extramedullary haemopoiesis 19.01 17.10 3 6503 6 29945966
Pancreatitis acute 18.10 17.10 25 6481 25670 29920302
Agranulocytosis 17.99 17.10 23 6483 21919 29924053
Aspartate aminotransferase increased 17.55 17.10 41 6465 63381 29882591
Rash 17.40 17.10 85 6421 191804 29754168
Bacteraemia 17.20 17.10 19 6487 15541 29930431
Fusarium infection 17.11 17.10 7 6499 1057 29944915

Pharmacologic Action:

SourceCodeDescription
ATC P01AX06 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
AGENTS AGAINST AMOEBIASIS AND OTHER PROTOZOAL DISEASES
Other agents against amoebiasis and other protozoal diseases
FDA EPC N0000175482 Antimalarial
FDA EPC N0000175485 Antiprotozoal
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000962 Antimalarials
MeSH PA D000977 Antiparasitic Agents
MeSH PA D000981 Antiprotozoal Agents
MeSH PA D004791 Enzyme Inhibitors
CHEBI has role CHEBI:35718 antifungal drug
CHEBI has role CHEBI:38068 antimalarials
CHEBI has role CHEBI:38503 nadh-coenzyme q oxidoreductase inhibitors
CHEBI has role CHEBI:77103 ec 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitors
CHEBI has role CHEBI:77106 quinol--cytochrome-c reductase (ec 1.10.2.2) inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Falciparum malaria indication 62676009 DOID:14067
Pneumocystosis jiroveci pneumonia indication 415125002 DOID:11339
Chloroquine-Resistant Plasmodium Falciparum Malaria Prevention indication
Plasmodium Falciparum Malaria Prevention indication
Pneumocystis Carinii Pneumonia Prevention indication
Babesiosis off-label use 21061004 DOID:9643
Vivax malaria off-label use 27052006 DOID:12978
Toxoplasmosis off-label use 187192000 DOID:9965
Toxoplasmosis associated with acquired immunodeficiency syndrome off-label use 421666009
Toxoplasmosis Prevention off-label use
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Hyperglycemia contraindication 80394007 DOID:4195
Anemia due to enzyme deficiency contraindication 111577008
Disease of liver contraindication 235856003 DOID:409
Chronic diarrhea contraindication 236071009
Vomiting contraindication 422400008
Malabsorption States contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.18 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme IC50 5.03 WOMBAT-PK
Cytochrome b Enzyme INHIBITOR CHEMBL CHEMBL
Ubiquinol-cytochrome-c reductase complex core protein I, mitochondrial Enzyme WOMBAT-PK
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme IC50 6.15 CHEMBL
Dihydroorotate dehydrogenase Unclassified Ki 4.57 CHEMBL

External reference:

IDSource
Y883P1Z2LT UNII
4020594 VUID
N0000148284 NUI
D00236 KEGG_DRUG
4020594 VANDF
C0700939 UMLSCUI
CHEBI:575568 CHEBI
AOQ PDB_CHEM_ID
CHEMBL1450 ChEMBL_ID
74989 PUBCHEM_CID
DB01117 DRUGBANK_ID
D053626 MESH_DESCRIPTOR_UI
6914 INN_ID
9695 IUPHAR_LIGAND_ID
114972 RXNORM
1907 MMSL
213467 MMSL
4227 MMSL
d01120 MMSL
004112 NDDF
108718008 SNOMEDCT_US
386899002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 0121-0888 SUSPENSION 750 mg ORAL ANDA 29 sections
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 0121-0898 SUSPENSION 750 mg ORAL ANDA 29 sections
MEPRON HUMAN PRESCRIPTION DRUG LABEL 1 0173-0547 SUSPENSION 750 mg ORAL NDA 25 sections
MEPRON HUMAN PRESCRIPTION DRUG LABEL 1 0173-0665 SUSPENSION 750 mg ORAL NDA 25 sections
MALARONE HUMAN PRESCRIPTION DRUG LABEL 2 0173-0675 TABLET, FILM COATED 250 mg ORAL NDA 24 sections
MALARONE HUMAN PRESCRIPTION DRUG LABEL 2 0173-0676 TABLET, FILM COATED 62.50 mg ORAL NDA 24 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 0378-4160 TABLET, FILM COATED 62.50 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 0378-4162 TABLET, FILM COATED 250 mg ORAL ANDA 27 sections
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 0904-7064 SUSPENSION 750 mg ORAL ANDA 24 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 10544-909 TABLET, FILM COATED 250 mg ORAL ANDA 26 sections
Atovaquone Oral Suspension HUMAN PRESCRIPTION DRUG LABEL 1 10702-223 SUSPENSION 750 mg ORAL ANDA 21 sections
atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 16714-900 SUSPENSION 750 mg ORAL ANDA 25 sections
Atovaquone Human Prescription Drug Label 1 31722-629 SUSPENSION 750 mg ORAL ANDA 24 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 33261-900 TABLET, FILM COATED 250 mg ORAL ANDA 22 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 42254-150 TABLET 250 mg ORAL ANDA 20 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 43063-393 TABLET, FILM COATED 250 mg ORAL ANDA 26 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 43063-522 TABLET, FILM COATED 250 mg ORAL NDA authorized generic 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 50090-1302 TABLET, FILM COATED 250 mg ORAL ANDA 26 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 50090-2980 TABLET, FILM COATED 250 mg ORAL NDA authorized generic 27 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 50090-2980 TABLET, FILM COATED 250 mg ORAL NDA authorized generic 27 sections
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 50268-086 SUSPENSION 750 mg ORAL ANDA 24 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 54868-6393 TABLET, FILM COATED 250 mg ORAL ANDA 22 sections
MALARONE HUMAN PRESCRIPTION DRUG LABEL 2 55289-747 TABLET, FILM COATED 250 mg ORAL NDA 24 sections
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 60687-534 SUSPENSION 750 mg ORAL ANDA 24 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 60760-498 TABLET, FILM COATED 250 mg ORAL ANDA 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 63187-879 TABLET, FILM COATED 250 mg ORAL ANDA 26 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 63629-5531 TABLET, FILM COATED 250 mg ORAL NDA authorized generic 26 sections
ATOVAQUONE HUMAN PRESCRIPTION DRUG LABEL 1 65162-693 SUSPENSION 750 mg ORAL ANDA 22 sections
Atovaquone HUMAN PRESCRIPTION DRUG LABEL 1 66689-062 SUSPENSION 750 mg ORAL ANDA 25 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 66993-060 TABLET, FILM COATED 250 mg ORAL NDA authorized generic 26 sections