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

Stem definitionDrug idCAS RN
4634 163451-81-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • HMR1726
  • flucyamide
  • aubagio
  • teriflunomide
Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis. The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.
  • Molecular weight: 270.21
  • Formula: C12H9F3N2O2
  • CLOGP: 2.13
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 73.12
  • ALOGS: -4.34
  • ROTB: 3

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
14 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.16 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.01 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 350 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Aug. 26, 2013 EMA
Sept. 12, 2012 FDA SANOFI AVENTIS US

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
Multiple sclerosis relapse 1600.03 16.88 617 20451 44236 53283762
Alopecia 1183.56 16.88 869 20199 233714 53094284
Multiple sclerosis 732.27 16.88 306 20762 26847 53301151
Paraesthesia 426.76 16.88 373 20695 127142 53200856
Hypoaesthesia 409.25 16.88 371 20697 132624 53195374
Diarrhoea 228.81 16.88 649 20419 624897 52703101
Product dose omission issue 206.98 16.88 312 20756 191308 53136690
Gait disturbance 148.23 16.88 242 20826 158600 53169398
Balance disorder 129.54 16.88 152 20916 73055 53254943
Fall 98.67 16.88 338 20730 358102 52969896
Rheumatoid arthritis 97.41 16.88 7 21061 314524 53013474
Product dose omission in error 95.55 16.88 32 21036 1503 53326495
Optic neuritis 92.53 16.88 49 21019 7286 53320712
Unevaluable event 91.24 16.88 105 20963 49393 53278605
Memory impairment 91.22 16.88 138 20930 84619 53243379
Fatigue 88.56 16.88 540 20528 729966 52598032
Off label use 83.88 16.88 41 21027 472171 52855827
Muscular weakness 73.41 16.88 138 20930 100854 53227144
Bladder disorder 73.03 16.88 43 21025 7845 53320153
Depressed mood 65.74 16.88 77 20991 36887 53291111
JC polyomavirus test positive 64.54 16.88 22 21046 1091 53326907
Acute kidney injury 62.97 16.88 12 21056 253856 53074142
Drug hypersensitivity 60.79 16.88 15 21053 265227 53062771
Central nervous system lesion 60.67 16.88 42 21026 10120 53317878
Toxicity to various agents 59.80 16.88 8 21060 219590 53108408
Depression 58.62 16.88 182 20886 182870 53145128
Headache 57.44 16.88 385 20683 536436 52791562
Magnetic resonance imaging abnormal 56.61 16.88 26 21042 2843 53325155
Visual impairment 54.67 16.88 101 20967 72811 53255187
Limb discomfort 50.16 16.88 56 21012 25466 53302532
Exposure during pregnancy 48.45 16.88 133 20935 124727 53203271
Burning sensation 44.44 16.88 73 20995 47940 53280058
Completed suicide 42.94 16.88 3 21065 138198 53189800
Condition aggravated 42.43 16.88 230 20838 296904 53031094
Hepatic enzyme increased 39.92 16.88 125 20943 126070 53201928
Maternal exposure during pregnancy 39.33 16.88 7 21061 155632 53172366
Lymphopenia 38.44 16.88 40 21028 16803 53311195
Mobility decreased 37.63 16.88 89 20979 76182 53251816
Sensory disturbance 37.60 16.88 35 21033 12851 53315147
Urinary incontinence 35.72 16.88 52 21016 30769 53297229
COVID-19 35.37 16.88 57 21011 36831 53291167
Electric shock sensation 35.37 16.88 9 21059 157 53327841
Breast cancer 35.27 16.88 67 21001 49291 53278707
Cognitive disorder 33.51 16.88 62 21006 44716 53283282
Drug interaction 33.21 16.88 23 21045 219306 53108692
Therapeutic product effect decreased 33.20 16.88 5 21063 125650 53202348
Death 32.59 16.88 57 21011 357175 52970823
Micturition urgency 32.38 16.88 27 21041 8575 53319423
Hyponatraemia 31.95 16.88 3 21065 108604 53219394
Synovitis 31.69 16.88 3 21065 107890 53220108
Injection site pain 31.16 16.88 4 21064 113387 53214611
Incontinence 31.00 16.88 29 21039 10714 53317284
Hypotension 30.75 16.88 33 21035 254043 53073955
Overdose 29.12 16.88 4 21064 107732 53220266
Feeling abnormal 28.23 16.88 117 20951 135184 53192814
Muscle spasticity 28.17 16.88 35 21033 17803 53310195
Decreased interest 28.10 16.88 17 21051 3256 53324742
Weight decreased 27.10 16.88 172 20896 234776 53093222
Joint swelling 26.73 16.88 32 21036 234606 53093392
Lipase increased 26.45 16.88 25 21043 9353 53318645
Anaemia 26.28 16.88 43 21025 276675 53051323
Hair texture abnormal 25.20 16.88 17 21051 3925 53324073
Heteroplasia 23.31 16.88 4 21064 7 53327991
Liver function test increased 22.65 16.88 39 21029 26589 53301409
Walking aid user 22.50 16.88 19 21049 6139 53321859
Pneumonia 22.39 16.88 84 20984 407085 52920913
Systemic lupus erythematosus 22.01 16.88 11 21057 125403 53202595
Blood pressure increased 21.54 16.88 111 20957 140368 53187630
Vision blurred 21.07 16.88 78 20990 85526 53242472
Muscle spasms 20.31 16.88 106 20962 134689 53193309
Pain in extremity 20.10 16.88 186 20882 284864 53043134
Haemoglobin decreased 19.98 16.88 15 21053 137292 53190706
Nausea 19.87 16.88 413 20655 755678 52572320
Paternal exposure timing unspecified 19.58 16.88 4 21064 24 53327974
Abortion 19.57 16.88 12 21056 2354 53325644
Lower respiratory tract infection 19.21 16.88 6 21062 90975 53237023
Band sensation 18.95 16.88 8 21060 715 53327283
Respiratory failure 18.90 16.88 8 21060 100504 53227494
Pharyngeal abscess 18.84 16.88 6 21062 240 53327758
Cardiac failure congestive 18.07 16.88 7 21061 92750 53235248
Onychoclasis 18.05 16.88 16 21052 5517 53322481
Progressive multiple sclerosis 17.99 16.88 8 21060 811 53327187
Temperature intolerance 17.95 16.88 19 21049 8134 53319864
Therapeutic product effect incomplete 17.76 16.88 7 21061 91777 53236221
Dysstasia 17.61 16.88 29 21039 19070 53308928
Granuloma annulare 17.55 16.88 7 21061 541 53327457
Pancytopenia 17.48 16.88 7 21061 90921 53237077
Hypertension 17.37 16.88 150 20918 225281 53102717
Encephalitis autoimmune 17.32 16.88 9 21059 1287 53326711
Secondary progressive multiple sclerosis 17.09 16.88 9 21059 1323 53326675

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
Multiple sclerosis relapse 676.88 25.30 178 3976 11603 32497769
Multiple sclerosis 351.14 25.30 97 4057 7547 32501825
Alopecia 182.41 25.30 76 4078 20654 32488718
Product dose omission issue 89.55 25.30 86 4068 102489 32406883
Gait disturbance 86.89 25.30 76 4078 80332 32429040
Hypoaesthesia 85.80 25.30 66 4088 58287 32451085
Paraesthesia 78.72 25.30 63 4091 58881 32450491
Diarrhoea 69.70 25.30 147 4007 364655 32144717
Balance disorder 56.55 25.30 44 4110 39415 32469957
Product dose omission in error 47.75 25.30 11 4143 404 32508968
Fatigue 42.72 25.30 119 4035 350582 32158790
Fall 35.95 25.30 78 4076 196123 32313249
Headache 34.81 25.30 77 4077 196120 32313252
Memory impairment 31.58 25.30 32 4122 40447 32468925
Meningoencephalitis herpetic 30.80 25.30 9 4145 848 32508524
Visual impairment 27.49 25.30 27 4127 32861 32476511
Unevaluable event 27.02 25.30 27 4127 33559 32475813

Pharmacologic Action:

SourceCodeDescription
ATC L04AA31 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
MeSH PA D000700 Analgesics
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D000894 Anti-Inflammatory Agents, Non-Steroidal
MeSH PA D018501 Antirheumatic Agents
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
FDA MoA N0000185501 Dihydroorotate Dehydrogenase Inhibitors
FDA EPC N0000185502 Pyrimidine Synthesis Inhibitor
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drugs
CHEBI has role CHEBI:38637 protein tyrosine kinase inhibitor
CHEBI has role CHEBI:49103 drug metabolites
CHEBI has role CHEBI:50908 agente hepatotoxico
CHEBI has role CHEBI:68542 DHODH inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple sclerosis indication 24700007 DOID:2377

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.59 acidic
pKa2 10.61 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
14MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL 6794410 Sept. 12, 2026 TREATMENT OF PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS
7MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL 6794410 Sept. 12, 2026 TREATMENT OF PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS
14MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL 9186346 Feb. 4, 2034 TREATMENT OF PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS WHILE MANAGING THE RISK OF TERIFLUNOMIDE AND ROSUVASTATIN INTERACTION BY LIMITING THE ROSUVASTATIN DOSE TO NO MORE THAN 10MG AND/OR ADMINISTERING ABOUT HALF THE NORMAL DOSE
7MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL 9186346 Feb. 4, 2034 TREATMENT OF PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS WHILE MANAGING THE RISK OF TERIFLUNOMIDE AND ROSUVASTATIN INTERACTION BY LIMITING THE ROSUVASTATIN DOSE TO NO MORE THAN 10MG AND/OR ADMINISTERING ABOUT HALF THE NORMAL DOSE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
14MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL April 30, 2024 REVISIONS TO LABELING BASED ON DATA SUBMITTED IN RESPONSE TO PEDIATRIC WRITTEN REQUEST
7MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL April 30, 2024 REVISIONS TO LABELING BASED ON DATA SUBMITTED IN RESPONSE TO PEDIATRIC WRITTEN REQUEST
14MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL Oct. 30, 2024 PEDIATRIC EXCLUSIVITY
7MG AUBAGIO SANOFI AVENTIS US N202992 Sept. 12, 2012 RX TABLET ORAL Oct. 30, 2024 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme INHIBITOR Ki 7.52 CHEMBL CHEMBL
Dihydrofolate reductase Enzyme IC50 6.41 CHEMBL
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme IC50 8.05 CHEMBL
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme IC50 7.16 CHEMBL
Dihydroorotate dehydrogenase Enzyme Ki 4.66 CHEMBL
Dihydroorotate dehydrogenase Enzyme IC50 4.30 CHEMBL

External reference:

IDSource
D10172 KEGG_DRUG
4031717 VANDF
CHEBI:68540 CHEBI
A26 PDB_CHEM_ID
CHEMBL973 ChEMBL_ID
C527525 MESH_SUPPLEMENTAL_RECORD_UI
6844 IUPHAR_LIGAND_ID
7761 INN_ID
DB08880 DRUGBANK_ID
1C058IKG3B UNII
54684141 PUBCHEM_CID
1310520 RXNORM
193228 MMSL
28846 MMSL
d07905 MMSL
014643 NDDF
703785006 SNOMEDCT_US
703786007 SNOMEDCT_US
C1718383 UMLSCUI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 0115-1565 TABLET, FILM COATED 14 mg ORAL ANDA 20 sections
Aubagio HUMAN PRESCRIPTION DRUG LABEL 1 58468-0210 TABLET, FILM COATED 14 mg ORAL NDA 32 sections
Aubagio HUMAN PRESCRIPTION DRUG LABEL 1 58468-0211 TABLET, FILM COATED 7 mg ORAL NDA 32 sections
teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 68462-311 TABLET, FILM COATED 7 mg ORAL ANDA 29 sections
teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 68462-312 TABLET, FILM COATED 14 mg ORAL ANDA 29 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69238-1303 TABLET, FILM COATED 7 mg ORAL ANDA 23 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69238-1304 TABLET, FILM COATED 14 mg ORAL ANDA 23 sections
Teriflunomide Human Prescription Drug Label 1 69539-032 TABLET, FILM COATED 7 mg ORAL ANDA 27 sections
Teriflunomide Human Prescription Drug Label 1 69539-033 TABLET, FILM COATED 14 mg ORAL ANDA 27 sections