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
Alopecia 2472.16 32.93 649 3825 21352 2332259
Diarrhoea 1081.15 32.93 490 3984 83074 2270537
Multiple sclerosis relapse 1028.84 32.93 283 4191 10660 2342951
Paraesthesia 754.48 32.93 263 4211 21825 2331786
Hypoaesthesia 718.29 32.93 248 4226 19967 2333644
Fatigue 514.79 32.93 301 4173 84572 2269039
Nausea 454.33 32.93 308 4166 111881 2241730
Headache 447.95 32.93 270 4204 79909 2273702
Gait disturbance 333.88 32.93 147 4327 22398 2331213
Fall 331.88 32.93 185 4289 46914 2306697
Multiple sclerosis 294.25 32.93 94 4380 5840 2347771
Rash 264.30 32.93 174 4300 59384 2294227
Product dose omission 262.85 32.93 148 4326 38109 2315502
Hepatic enzyme increased 248.06 32.93 94 4380 9708 2343903
Pain 239.19 32.93 166 4308 61691 2291920
Unevaluable event 238.53 32.93 89 4385 8802 2344809
Weight decreased 234.12 32.93 124 4350 28247 2325364
Condition aggravated 228.40 32.93 127 4347 31852 2321759
Exposure during pregnancy 201.67 32.93 108 4366 25111 2328500
Asthenia 193.02 32.93 131 4343 46795 2306816
Balance disorder 192.00 32.93 78 4396 9669 2343942
Muscular weakness 184.75 32.93 86 4388 14811 2338800
Pruritus 182.98 32.93 123 4351 43217 2310394
Pain in extremity 177.82 32.93 120 4354 42420 2311191
Dizziness 175.51 32.93 135 4339 58530 2295081
Drug ineffective 172.46 32.93 169 4305 101455 2252156
Abdominal discomfort 162.97 32.93 83 4391 17373 2336238
Depression 161.40 32.93 97 4377 28035 2325576
Hypertension 158.67 32.93 95 4379 27266 2326345
Abdominal pain upper 141.91 32.93 82 4392 22018 2331593
Memory impairment 139.95 32.93 68 4406 12855 2340756
Vomiting 138.08 32.93 128 4346 71474 2282137
Urinary tract infection 131.00 32.93 87 4387 29855 2323756
Burning sensation 125.05 32.93 54 4420 7774 2345837
Malaise 118.05 32.93 105 4369 55480 2298131
Alanine aminotransferase increased 117.31 32.93 62 4412 13970 2339641
Blood pressure increased 116.95 32.93 66 4408 16920 2336691
Abdominal pain 113.32 32.93 84 4390 34290 2319321
Neuropathy peripheral 111.38 32.93 56 4418 11376 2342235
Visual impairment 109.90 32.93 56 4418 11699 2341912
Central nervous system lesion 107.03 32.93 34 4440 2060 2351551
Dyspnoea 106.13 32.93 116 4358 78617 2274994
Feeling abnormal 104.22 32.93 69 4405 23512 2330099
Vision blurred 103.68 32.93 58 4416 14610 2339001
Breast cancer 102.85 32.93 50 4424 9445 2344166
Back pain 101.26 32.93 76 4398 31583 2322028
Insomnia 93.97 32.93 67 4407 25720 2327891
Contusion 91.46 32.93 51 4423 12759 2340852
Optic neuritis 89.41 32.93 28 4446 1618 2351993
Decreased appetite 84.97 32.93 66 4408 28825 2324786
Nasopharyngitis 79.62 32.93 57 4417 21999 2331612
Muscle spasms 78.46 32.93 56 4418 21510 2332101
Depressed mood 76.93 32.93 34 4440 5164 2348447
Gastrointestinal disorder 76.17 32.93 40 4434 8877 2344734
Lymphopenia 74.67 32.93 27 4447 2427 2351184
Magnetic resonance imaging abnormal 72.18 32.93 20 4454 751 2352860
Liver function test increased 72.05 32.93 28 4446 3073 2350538
Pyrexia 70.21 32.93 78 4396 53630 2299981
Limb discomfort 69.72 32.93 28 4446 3351 2350260
Erythema 66.49 32.93 54 4420 25105 2328506
Arthralgia 66.11 32.93 76 4398 54209 2299402
Hot flush 60.63 32.93 32 4442 7167 2346444
Urinary incontinence 60.42 32.93 27 4447 4206 2349405
Migraine 59.02 32.93 36 4438 10617 2342994
Loss of personal independence in daily activities 54.57 32.93 27 4447 5284 2348327
Dry skin 54.41 32.93 29 4445 6623 2346988
Cognitive disorder 54.24 32.93 27 4447 5354 2348257
Abortion spontaneous 53.71 32.93 37 4437 13408 2340203
Incontinence 51.84 32.93 18 4456 1436 2352175
Pneumonia 50.11 32.93 63 4411 49233 2304378
Chest pain 49.55 32.93 48 4426 28089 2325522
Hepatocellular injury 48.87 32.93 23 4451 4032 2349579
Blister 48.39 32.93 27 4447 6744 2346867
Influenza 47.84 32.93 34 4440 12944 2340667
Anxiety 47.82 32.93 48 4426 29311 2324300
Heart rate increased 47.78 32.93 32 4442 11073 2342538
Micturition urgency 46.53 32.93 16 4458 1240 2352371
Drug intolerance 46.15 32.93 34 4440 13683 2339928
JC polyomavirus test positive 45.20 32.93 11 4463 245 2353366
Product use issue 45.13 32.93 32 4442 12137 2341474
Palpitations 44.87 32.93 36 4438 16420 2337191
Skin exfoliation 43.88 32.93 24 4450 5766 2347845
Rash pruritic 43.10 32.93 26 4448 7509 2346102
Walking aid user 41.87 32.93 13 4461 729 2352882
Bronchitis 41.70 32.93 32 4442 13682 2339929
White blood cell count decreased 41.69 32.93 36 4438 18172 2335439
Hair texture abnormal 41.33 32.93 12 4462 534 2353077
Cough 41.31 32.93 47 4427 33070 2320541
Influenza like illness 40.68 32.93 30 4444 12084 2341527
Neuralgia 40.26 32.93 18 4456 2804 2350807
Aspartate aminotransferase increased 39.60 32.93 30 4444 12582 2341029
Mobility decreased 39.37 32.93 26 4448 8784 2344827
Pollakiuria 38.30 32.93 19 4455 3737 2349874
Decreased interest 38.09 32.93 11 4463 480 2353131
Hypersensitivity 37.35 32.93 38 4436 23555 2330056
Hemiparesis 36.81 32.93 18 4456 3432 2350179
Lipase increased 36.81 32.93 14 4460 1448 2352163
Peripheral swelling 36.69 32.93 33 4441 17564 2336047
Liver function test abnormal 35.65 32.93 23 4451 7467 2346144
Tooth abscess 35.32 32.93 15 4459 2064 2351547
Acne 35.17 32.93 17 4457 3159 2350452
Flatulence 34.96 32.93 19 4455 4506 2349105
Lymphocyte count decreased 34.25 32.93 17 4457 3346 2350265
Myalgia 34.09 32.93 36 4438 23297 2330314
Pancreatitis 34.07 32.93 23 4451 8056 2345555
Speech disorder 33.64 32.93 21 4453 6443 2347168
Vertigo 33.23 32.93 24 4450 9360 2344251

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 444.20 39.72 95 1043 3005 1742638
Diarrhoea 256.00 39.72 121 1017 53731 1691912
Alopecia 230.70 39.72 58 1080 3695 1741948
Hypoaesthesia 143.81 39.72 50 1088 9785 1735858
Gait disturbance 135.08 39.72 51 1087 12619 1733024
Paraesthesia 125.74 39.72 46 1092 10405 1735238
Fatigue 119.62 39.72 72 1066 50709 1694934
Multiple sclerosis 116.16 39.72 30 1108 2102 1743541
Product dose omission 106.95 39.72 51 1087 22389 1723254
Fall 97.62 39.72 51 1087 27163 1718480
Asthenia 94.05 39.72 54 1084 34616 1711027
Headache 89.11 39.72 52 1086 34324 1711319
Drug ineffective 81.44 39.72 62 1076 63739 1681904
Unevaluable event 66.51 39.72 25 1113 6041 1739602
Weight decreased 65.69 39.72 37 1101 22716 1722927
Pain 60.24 39.72 37 1101 26620 1719023
Rash 56.72 39.72 41 1097 38652 1706991
Alanine aminotransferase increased 55.51 39.72 27 1111 12251 1733392
Depression 50.46 39.72 28 1110 16641 1729002
Memory impairment 50.37 39.72 21 1117 6642 1739001
Balance disorder 49.66 39.72 20 1118 5792 1739851
Nausea 48.61 39.72 42 1096 51154 1694489
Muscular weakness 47.69 39.72 23 1115 10226 1735417
Pain in extremity 45.15 39.72 27 1111 18445 1727198
Hepatic enzyme increased 40.59 39.72 18 1120 6603 1739040

Pharmacologic Action:

SourceCodeDescription
ATC L04AA31 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drug
FDA EPC N0000185502 Pyrimidine Synthesis Inhibitor
FDA MoA N0000185501 Dihydroorotate Dehydrogenase 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)

None

Bioactivity Summary:

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

External reference:

IDSource
D10172 KEGG_DRUG
C3497721 UMLSCUI
1C058IKG3B UNII
7761 INN_ID
CHEMBL973 ChEMBL_ID
DB08880 DRUGBANK_ID
CHEBI:68540 CHEBI
54684141 PUBCHEM_CID
6844 IUPHAR_LIGAND_ID
C527525 MESH_SUPPLEMENTAL_RECORD_UI
703786007 SNOMEDCT_US
1310520 RXNORM
28846 MMSL
d07905 MMSL
014643 NDDF
4031717 VANDF
703785006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Aubagio HUMAN PRESCRIPTION DRUG LABEL 1 58468-0210 TABLET, FILM COATED 14 mg ORAL NDA 20 sections
Aubagio HUMAN PRESCRIPTION DRUG LABEL 1 58468-0211 TABLET, FILM COATED 7 mg ORAL NDA 20 sections
teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 68462-311 TABLET, FILM COATED 7 mg ORAL ANDA 19 sections
teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 68462-312 TABLET, FILM COATED 14 mg ORAL ANDA 19 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69238-1303 TABLET, FILM COATED 7 mg ORAL ANDA 19 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69238-1304 TABLET, FILM COATED 14 mg ORAL ANDA 19 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69539-032 TABLET, FILM COATED 7 mg ORAL ANDA 19 sections
Teriflunomide HUMAN PRESCRIPTION DRUG LABEL 1 69539-033 TABLET, FILM COATED 14 mg ORAL ANDA 19 sections