Details of the Drug

General Information of Drug (ID: DMR8ONJ)

• Drug Name: Leflunomide
• Synonyms: Arava; Leflunomid; Leflunomida; Leflunomidum; Lefunamide; Aventis Behring Brand of Leflunomide; Aventis Brand of Leflunomide; Aventis Pharma Brand of Leflunomide; Hoechst Brand of Leflunomide; HWA 486; L 5025; SU 101; SU101; Arava (TN); Arava, Leflunomide; HWA-486; Leflunomida [INN-Spanish]; Leflunomide [USAN:INN]; Leflunomidum [INN-Latin]; Lefunomide [Inn-Spanish]; RS-34821; SU 101 (pharmaceutical); SU-101; AP-501/42475599; Leflunomide (JAN/USAN/INN); N-(4-trifluoromethyphenyl)-5-methylisoxazole-4-carboxamide; N-(4'-Trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide; Alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidide; 4-Isoxazolecarboxamide, 5-methyl-N-(4-(trifluoromethyl)phenyl; 4-isoxazolecarboxamide,5-methyl-N-(4-(trifluoromethyl)phenyl); 5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide; 5-Methylisoxazole-4-(4-trifluoromethyl)carboxanilide; 5-Methylisoxazole-4-(4-trifluoromethylcarboxanilide); 5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide; 5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide; 5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide; 5-methyl-N-[4-(trifluoromethyl)phenyl]isoxazole-4-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Arthritis	FA20	Approved	[1]
Lupus nephritis	4A40.0Y	Approved	[2]
Multiple sclerosis	8A40	Approved	[3]
Psoriatic arthritis	FA21	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[4]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 270.21
  Logarithm of the Partition Coefficient (xlogp); 2.5
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [5]
  Bioavailability: 80% of drug becomes completely available to its intended biological destination(s) [6]
  Elimination: 1% of drug is excreted from urine in the unchanged form [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.23236 micromolar/kg/day [7]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.023 mg/mL [5]
• Chemical Identifiers:
  Formula: C12H9F3N2O2
  IUPAC Name: 5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
  Canonical SMILES: CC1=C(C=NO1)C(=O)NC2=CC=C(C=C2)C(F)(F)F
  InChI: InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)
  InChIKey: VHOGYURTWQBHIL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3899
  ChEBI ID: CHEBI:6402
  CAS Number: 75706-12-6
  DrugBank ID: DB01097
  TTD ID: D08ROP
  VARIDT ID: DR00130
  INTEDE ID: DR0921
  ACDINA ID: D00352
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[8]
HUMAN dihydroorotate dehydrogenase (DHODH)	TT3UY29	PYRD_HUMAN	Inhibitor	[9]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[11]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[12]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[13]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[14]
1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon (AGPAT5)	OTNY3VMD	PLCE_HUMAN	Gene/Protein Processing	[14]
10 kDa heat shock protein, mitochondrial (HSPE1)	OT7JSZLB	CH10_HUMAN	Gene/Protein Processing	[14]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Gene/Protein Processing	[14]
182 kDa tankyrase-1-binding protein (TNKS1BP1)	OTBIZECQ	TB182_HUMAN	Gene/Protein Processing	[14]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)	OTB8HCED	CN37_HUMAN	Gene/Protein Processing	[14]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Gene/Protein Processing	[14]
26S proteasome non-ATPase regulatory subunit 12 (PSMD12)	OTWICA51	PSD12_HUMAN	Gene/Protein Processing	[14]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D)	OT1RWFV0	PDE4D_HUMAN	Gene/Protein Processing	[14]
3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 (FUT3)	OTXQ6P8R	FUT3_HUMAN	Gene/Protein Processing	[14]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Leflunomide

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Salsalate	DM13P4C	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Salsalate.	Rheumatoid arthritis [FA20]	[15]
Baricitinib	DM4ONW5	Major	Additive immunosuppressive effects by the combination of Leflunomide and Baricitinib.	Rheumatoid arthritis [FA20]	[16]
Canakinumab	DM8HLO5	Major	Additive immunosuppressive effects by the combination of Leflunomide and Canakinumab.	Rheumatoid arthritis [FA20]	[16]
Tofacitinib	DMBS370	Major	Additive myelosuppressive effects by the combination of Leflunomide and Tofacitinib.	Rheumatoid arthritis [FA20]	[16]
Rilonacept	DMGLUQS	Major	Additive immunosuppressive effects by the combination of Leflunomide and Rilonacept.	Rheumatoid arthritis [FA20]	[16]
Dexamethasone	DMMWZET	Major	Additive immunosuppressive effects by the combination of Leflunomide and Dexamethasone.	Rheumatoid arthritis [FA20]	[16]

Coadministration of a Drug Treating the Disease Different from Leflunomide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Leflunomide and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[17]
Nicotinamide	DMUPE07	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Nicotinamide.	Acquired cutaneous blood vessel malformation [EF20]	[18]
Pioglitazone	DMKJ485	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Pioglitazone.	Acute diabete complication [5A2Y]	[18]
Tagraxofusp	DM9HQ5U	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Tagraxofusp.	Acute myeloid leukaemia [2A60]	[18]
Midostaurin	DMI6E0R	Major	Additive myelosuppressive effects by the combination of Leflunomide and Midostaurin.	Acute myeloid leukaemia [2A60]	[16]
Idarubicin	DMM0XGL	Major	Additive myelosuppressive effects by the combination of Leflunomide and Idarubicin.	Acute myeloid leukaemia [2A60]	[16]
Gilteritinib	DMTI0ZO	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Gilteritinib.	Acute myeloid leukaemia [2A60]	[18]
Inotersen	DMJ93CT	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Inotersen.	Amyloidosis [5D00]	[18]
Siltuximab	DMGEATB	Major	Additive immunosuppressive effects by the combination of Leflunomide and Siltuximab.	Anemia [3A00-3A9Z]	[16]
Dronedarone	DMA8FS5	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Dronedarone.	Angina pectoris [BA40]	[18]
Bedaquiline	DM3906J	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[18]
Oxymetholone	DMFXUT8	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Oxymetholone.	Aplastic anaemia [3A70]	[18]
Posaconazole	DMUL5EW	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Posaconazole.	Aspergillosis [1F20]	[18]
Budesonide	DMJIBAW	Major	Additive immunosuppressive effects by the combination of Leflunomide and Budesonide.	Asthma [CA23]	[16]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Leflunomide and Roflumilast.	Asthma [CA23]	[19]
Dupilumab	DMOAD2Y	Major	Additive immunosuppressive effects by the combination of Leflunomide and Dupilumab.	Atopic eczema [EA80]	[16]
Clarithromycin	DM4M1SG	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Clarithromycin.	Bacterial infection [1A00-1C4Z]	[18]
Levofloxacin	DMS60RB	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Levofloxacin.	Bacterial infection [1A00-1C4Z]	[18]
Troleandomycin	DMUZNIG	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Troleandomycin.	Bacterial infection [1A00-1C4Z]	[18]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[20]
Lomustine	DMMWSUL	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Lomustine.	Brain cancer [2A00]	[16]
Eribulin	DM1DX4Q	Major	Additive immunosuppressive effects by the combination of Leflunomide and Eribulin.	Breast cancer [2C60-2C6Y]	[16]
Talazoparib	DM1KS78	Major	Additive myelosuppressive effects by the combination of Leflunomide and Talazoparib.	Breast cancer [2C60-2C6Y]	[16]
Ixabepilone	DM2OZ3G	Major	Additive immunosuppressive effects by the combination of Leflunomide and Ixabepilone.	Breast cancer [2C60-2C6Y]	[16]
Lapatinib	DM3BH1Y	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Lapatinib.	Breast cancer [2C60-2C6Y]	[18]
LY2835219	DM93VBZ	Major	Additive myelosuppressive effects by the combination of Leflunomide and LY2835219.	Breast cancer [2C60-2C6Y]	[16]
Pralatrexate	DMAO80I	Major	Additive immunosuppressive effects by the combination of Leflunomide and Pralatrexate.	Breast cancer [2C60-2C6Y]	[16]
Tucatinib	DMBESUA	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Tucatinib.	Breast cancer [2C60-2C6Y]	[18]
Palbociclib	DMD7L94	Major	Additive myelosuppressive effects by the combination of Leflunomide and Palbociclib.	Breast cancer [2C60-2C6Y]	[16]
Thiotepa	DMIZKOP	Major	Additive myelosuppressive effects by the combination of Leflunomide and Thiotepa.	Breast cancer [2C60-2C6Y]	[16]
Cabazitaxel	DMPAZHC	Major	Additive myelosuppressive effects by the combination of Leflunomide and Cabazitaxel.	Breast cancer [2C60-2C6Y]	[16]
Bosutinib	DMTI8YE	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Bosutinib.	Breast cancer [2C60-2C6Y]	[16]
Trastuzumab Emtansine	DMU1LXS	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[18]
Fluoxymesterone	DMUHCF1	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Fluoxymesterone.	Breast cancer [2C60-2C6Y]	[18]
Fenofibric acid	DMGO2MC	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Fenofibric acid.	Cardiovascular disease [BA00-BE2Z]	[18]
Macitentan	DMP79A1	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Macitentan.	Cardiovascular disease [BA00-BE2Z]	[18]
Chenodiol	DMQ8JIK	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Chenodiol.	Cholelithiasis [DC11]	[18]
Corticotropin	DMP9TWZ	Major	Additive immunosuppressive effects by the combination of Leflunomide and Corticotropin.	Chronic kidney disease [GB61]	[16]
Anisindione	DM2C48U	Moderate	Decreased metabolism of Leflunomide caused by Anisindione mediated inhibition of CYP450 enzyme.	Coagulation defect [3B10]	[21]
Regorafenib	DMHSY1I	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Regorafenib.	Colorectal cancer [2B91]	[18]
Intedanib	DMSTA36	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Intedanib.	Colorectal cancer [2B91]	[18]
Aflibercept	DMT3D5I	Major	Additive immunosuppressive effects by the combination of Leflunomide and Aflibercept.	Colorectal cancer [2B91]	[16]
Capecitabine	DMTS85L	Major	Additive myelosuppressive effects by the combination of Leflunomide and Capecitabine.	Colorectal cancer [2B91]	[16]
Pasireotide	DMHM7JS	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Pasireotide.	Cushing syndrome [5A70]	[18]
Ivacaftor	DMZC1HS	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Ivacaftor.	Cystic fibrosis [CA25]	[18]
Nefazodone	DM4ZS8M	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Nefazodone.	Depression [6A70-6A7Z]	[18]
Milnacipran	DMBFE74	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Milnacipran.	Depression [6A70-6A7Z]	[18]
Polatuzumab vedotin	DMF6Y0L	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Polatuzumab vedotin.	Diffuse large B-cell lymphoma [2A81]	[16]
Lisocabtagene maraleucel	DMP45ME	Major	Additive immunosuppressive effects by the combination of Leflunomide and Lisocabtagene maraleucel.	Diffuse large B-cell lymphoma [2A81]	[16]
Axicabtagene ciloleucel	DMYHN59	Major	Additive myelosuppressive effects by the combination of Leflunomide and Axicabtagene ciloleucel.	Diffuse large B-cell lymphoma [2A81]	[16]
Fosphenytoin	DMOX3LB	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Fosphenytoin.	Epilepsy/seizure [8A61-8A6Z]	[18]
Cannabidiol	DM0659E	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Cannabidiol.	Epileptic encephalopathy [8A62]	[18]
Dantrolene	DM1D8XY	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Dantrolene.	Fever [MG26]	[18]
Bay 80-6946	DMLOS5R	Major	Additive myelosuppressive effects by the combination of Leflunomide and Bay 80-6946.	Follicular lymphoma [2A80]	[16]
Atovaquone	DMY4UMW	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Atovaquone.	Fungal infection [1F29-1F2F]	[18]
Sunitinib	DMCBJSR	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Sunitinib.	Gastrointestinal stromal tumour [2B5B]	[18]
Avapritinib	DMK2GZX	Major	Additive immunosuppressive effects by the combination of Leflunomide and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[16]
177Lu-DOTATATE	DMT8GVU	Major	Additive immunosuppressive effects by the combination of Leflunomide and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[16]
Procarbazine	DMIK367	Major	Additive immunosuppressive effects by the combination of Leflunomide and Procarbazine.	Hodgkin lymphoma [2B30]	[16]
Brentuximab vedotin	DMWLC57	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[16]
Rilpivirine	DMJ0QOW	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Rilpivirine.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Darunavir	DMN3GCH	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Darunavir.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Maraviroc	DMTL94F	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Maraviroc.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[18]
Rosuvastatin	DMMIQ7G	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Rosuvastatin.	Hyper-lipoproteinaemia [5C80]	[17]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[18]
Captopril	DM458UM	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Captopril.	Hypertension [BA00-BA04]	[18]
Tolvaptan	DMIWFRL	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Tolvaptan.	Hypo-osmolality/hyponatraemia [5C72]	[18]
Pirfenidone	DM6VZFQ	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Pirfenidone.	Idiopathic interstitial pneumonitis [CB03]	[18]
Givosiran	DM5PFIJ	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[18]
Febuxostat	DMDEXQ0	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Febuxostat.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[18]
Lesinurad	DMUR64T	Moderate	Decreased metabolism of Leflunomide caused by Lesinurad mediated inhibition of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[22]
Olaratumab	DMNYOIX	Major	Additive immunosuppressive effects by the combination of Leflunomide and Olaratumab.	Kaposi sarcoma [2B57]	[16]
Nelarabine	DMB6VEG	Major	Additive myelosuppressive effects by the combination of Leflunomide and Nelarabine.	Leukaemia [2A60-2B33]	[16]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Leflunomide and Denosumab.	Low bone mass disorder [FB83]	[23]
Crizotinib	DM4F29C	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Crizotinib.	Lung cancer [2C25]	[18]
Brigatinib	DM7W94S	Major	Additive immunosuppressive effects by the combination of Leflunomide and Brigatinib.	Lung cancer [2C25]	[16]
Ceritinib	DMB920Z	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Ceritinib.	Lung cancer [2C25]	[18]
Lurbinectedin	DMEFRTZ	Major	Additive immunosuppressive effects by the combination of Leflunomide and Lurbinectedin.	Lung cancer [2C25]	[16]
Alectinib	DMP1I6Y	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Alectinib.	Lung cancer [2C25]	[18]
Osimertinib	DMRJLAT	Major	Additive immunosuppressive effects by the combination of Leflunomide and Osimertinib.	Lung cancer [2C25]	[16]
BIBW 2992	DMTKD7Q	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and BIBW 2992.	Lung cancer [2C25]	[18]
Capmatinib	DMYCXKL	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Capmatinib.	Lung cancer [2C25]	[18]
Selpercatinib	DMZR15V	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Selpercatinib.	Lung cancer [2C25]	[18]
Belimumab	DM3OBQF	Major	Additive immunosuppressive effects by the combination of Leflunomide and Belimumab.	Lupus erythematosus [4A40]	[16]
Inotuzumab ozogamicin	DMAC130	Major	Additive immunosuppressive effects by the combination of Leflunomide and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[16]
Calaspargase pegol	DMQZBXI	Major	Additive immunosuppressive effects by the combination of Leflunomide and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[16]
Ofatumumab	DM295PR	Major	Additive myelosuppressive effects by the combination of Leflunomide and Ofatumumab.	Mature B-cell leukaemia [2A82]	[16]
Obinutuzumab	DM3BVAE	Major	Additive immunosuppressive effects by the combination of Leflunomide and Obinutuzumab.	Mature B-cell leukaemia [2A82]	[16]
Idelalisib	DM602WT	Major	Additive myelosuppressive effects by the combination of Leflunomide and Idelalisib.	Mature B-cell leukaemia [2A82]	[16]
GDC-0199	DMH0QKA	Major	Additive myelosuppressive effects by the combination of Leflunomide and GDC-0199.	Mature B-cell leukaemia [2A82]	[16]
IPI-145	DMWA24P	Major	Additive myelosuppressive effects by the combination of Leflunomide and IPI-145.	Mature B-cell leukaemia [2A82]	[16]
Acalabrutinib	DM7GCVW	Major	Additive myelosuppressive effects by the combination of Leflunomide and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[16]
Blinatumomab	DMGECIJ	Major	Additive immunosuppressive effects by the combination of Leflunomide and Blinatumomab.	Mature B-cell lymphoma [2A85]	[16]
Ibrutinib	DMHZCPO	Major	Additive myelosuppressive effects by the combination of Leflunomide and Ibrutinib.	Mature B-cell lymphoma [2A85]	[16]
Tisagenlecleucel	DMM9BJD	Major	Additive immunosuppressive effects by the combination of Leflunomide and Tisagenlecleucel.	Mature B-cell lymphoma [2A85]	[16]
Ponatinib	DMYGJQO	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Ponatinib.	Mature B-cell lymphoma [2A85]	[16]
Arry-162	DM1P6FR	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Arry-162.	Melanoma [2C30]	[18]
Vemurafenib	DM62UG5	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Vemurafenib.	Melanoma [2C30]	[18]
Ipilimumab	DMJTIYK	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Ipilimumab.	Melanoma [2C30]	[18]
Danazol	DML8KTN	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Danazol.	Menstrual cycle bleeding disorder [GA20]	[18]
Exjade	DMHPRWG	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Exjade.	Mineral absorption/transport disorder [5C64]	[18]
Carfilzomib	DM48K0X	Major	Additive myelosuppressive effects by the combination of Leflunomide and Carfilzomib.	Multiple myeloma [2A83]	[16]
Panobinostat	DM58WKG	Major	Additive immunosuppressive effects by the combination of Leflunomide and Panobinostat.	Multiple myeloma [2A83]	[16]
Selinexor	DMBD4K3	Major	Additive myelosuppressive effects by the combination of Leflunomide and Selinexor.	Multiple myeloma [2A83]	[16]
Belantamab mafodotin	DMBT3AI	Major	Additive myelosuppressive effects by the combination of Leflunomide and Belantamab mafodotin.	Multiple myeloma [2A83]	[16]
Elotuzumab	DMEYHG9	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Elotuzumab.	Multiple myeloma [2A83]	[16]
Daratumumab	DMKCIUZ	Major	Additive immunosuppressive effects by the combination of Leflunomide and Daratumumab.	Multiple myeloma [2A83]	[16]
Tecfidera	DM2OVDT	Major	Additive immunosuppressive effects by the combination of Leflunomide and Tecfidera.	Multiple sclerosis [8A40]	[16]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Leflunomide and Siponimod.	Multiple sclerosis [8A40]	[17]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Leflunomide and Fingolimod.	Multiple sclerosis [8A40]	[16]
Ocrelizumab	DMEZ2KH	Major	Additive immunosuppressive effects by the combination of Leflunomide and Ocrelizumab.	Multiple sclerosis [8A40]	[16]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Leflunomide and Ozanimod.	Multiple sclerosis [8A40]	[19]
Romidepsin	DMT5GNL	Major	Additive immunosuppressive effects by the combination of Leflunomide and Romidepsin.	Mycosis fungoides [2B01]	[16]
Decitabine	DMQL8XJ	Major	Additive immunosuppressive effects by the combination of Leflunomide and Decitabine.	Myelodysplastic syndrome [2A37]	[16]
Fedratinib	DM4ZBK6	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Fedratinib.	Myeloproliferative neoplasm [2A20]	[18]
Ruxolitinib	DM7Q98D	Major	Additive myelosuppressive effects by the combination of Leflunomide and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[16]
Dasatinib	DMJV2EK	Major	Additive myelosuppressive effects by the combination of Leflunomide and Dasatinib.	Myeloproliferative neoplasm [2A20]	[16]
Omacetaxine mepesuccinate	DMPU2WX	Major	Additive immunosuppressive effects by the combination of Leflunomide and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[16]
Inebilizumab	DMI0RHA	Major	Additive immunosuppressive effects by the combination of Leflunomide and Inebilizumab.	Nervous system paraneoplastic/autoimmune disorder [8E4A]	[16]
Bupropion	DM5PCS7	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Bupropion.	Nicotine use disorder [6C4A]	[18]
Atezolizumab	DMMF8U0	Major	Additive immunosuppressive effects by the combination of Leflunomide and Atezolizumab.	Non-small cell lung cancer [2C25]	[16]
Entrectinib	DMMPTLH	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Entrectinib.	Non-small cell lung cancer [2C25]	[16]
Olaparib	DM8QB1D	Major	Additive myelosuppressive effects by the combination of Leflunomide and Olaparib.	Ovarian cancer [2C73]	[16]
Rucaparib	DM9PVX8	Major	Additive immunosuppressive effects by the combination of Leflunomide and Rucaparib.	Ovarian cancer [2C73]	[16]
MK-4827	DMLYGH4	Major	Additive myelosuppressive effects by the combination of Leflunomide and MK-4827.	Ovarian cancer [2C73]	[16]
Choline salicylate	DM8P137	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[15]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Leflunomide caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[24]
ABIRATERONE	DM8V75C	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and ABIRATERONE.	Prostate cancer [2C82]	[18]
Bicalutamide	DMZMSPF	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Bicalutamide.	Prostate cancer [2C82]	[18]
Brodalumab	DMASDQ6	Major	Additive immunosuppressive effects by the combination of Leflunomide and Brodalumab.	Psoriasis [EA90]	[16]
Ustekinumab	DMHTYK3	Major	Additive immunosuppressive effects by the combination of Leflunomide and Ustekinumab.	Psoriasis [EA90]	[16]
Tildrakizumab	DMLW9HG	Major	Additive immunosuppressive effects by the combination of Leflunomide and Tildrakizumab.	Psoriasis [EA90]	[16]
Risankizumab	DMM32GT	Major	Additive immunosuppressive effects by the combination of Leflunomide and Risankizumab.	Psoriasis [EA90]	[16]
Ixekizumab	DMXW92T	Major	Additive immunosuppressive effects by the combination of Leflunomide and Ixekizumab.	Psoriasis [EA90]	[16]
Ambrisentan	DMD1QXW	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Ambrisentan.	Pulmonary hypertension [BB01]	[18]
Axitinib	DMGVH6N	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Axitinib.	Renal cell carcinoma [2C90]	[18]
Temsirolimus	DMS104F	Major	Additive immunosuppressive effects by the combination of Leflunomide and Temsirolimus.	Renal cell carcinoma [2C90]	[16]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Leflunomide when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[25]
Mogamulizumab	DMISH0Z	Major	Additive myelosuppressive effects by the combination of Leflunomide and Mogamulizumab.	Sezary syndrome [2B02]	[16]
Larotrectinib	DM26CQR	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[18]
PDX-101	DM6OC53	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and PDX-101.	Solid tumour/cancer [2A00-2F9Z]	[16]
Ifosfamide	DMCT3I8	Major	Additive myelosuppressive effects by the combination of Leflunomide and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[16]
Docetaxel	DMDI269	Major	Additive immunosuppressive effects by the combination of Leflunomide and Docetaxel.	Solid tumour/cancer [2A00-2F9Z]	[16]
Trabectedin	DMG3Y89	Major	Additive immunosuppressive effects by the combination of Leflunomide and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[16]
Mitoxantrone	DMM39BF	Major	Additive immunosuppressive effects by the combination of Leflunomide and Mitoxantrone.	Solid tumour/cancer [2A00-2F9Z]	[16]
LEE011	DMMX75K	Major	Additive immunosuppressive effects by the combination of Leflunomide and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[16]
Taxol	DMUOT9V	Major	Additive myelosuppressive effects by the combination of Leflunomide and Taxol.	Solid tumour/cancer [2A00-2F9Z]	[16]
Methyltestosterone	DMWLFGO	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Methyltestosterone.	Solid tumour/cancer [2A00-2F9Z]	[18]
Pomalidomide	DMTGBAX	Major	Additive myelosuppressive effects by the combination of Leflunomide and Pomalidomide.	Systemic sclerosis [4A42]	[16]
Plicamycin	DM7C8YV	Major	Additive myelosuppressive effects by the combination of Leflunomide and Plicamycin.	Testicular cancer [2C80]	[16]
Fostamatinib	DM6AUHV	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Fostamatinib.	Thrombocytopenia [3B64]	[18]
Eltrombopag	DMOGFIX	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Eltrombopag.	Thrombocytopenia [3B64]	[18]
Lenvatinib	DMB1IU4	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Lenvatinib.	Thyroid cancer [2D10]	[18]
Trimetrexate	DMDEA85	Major	Additive immunosuppressive effects by the combination of Leflunomide and Trimetrexate.	Toxoplasmosis [1F57]	[16]
Belatacept	DMXLYQF	Major	Additive immunosuppressive effects by the combination of Leflunomide and Belatacept.	Transplant rejection [NE84]	[16]
Tolbutamide	DM02AWV	Moderate	Decreased metabolism of Leflunomide caused by Tolbutamide mediated inhibition of CYP450 enzyme.	Type 2 diabetes mellitus [5A11]	[16]
Durvalumab	DM4PVDY	Major	Additive immunosuppressive effects by the combination of Leflunomide and Durvalumab.	Ureteral cancer [2C92]	[16]
Elagolix	DMB2C0E	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Elagolix.	Uterine fibroid [2E86]	[18]
Amiodarone	DMUTEX3	Major	Increased risk of hepatotoxicity by the combination of Leflunomide and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[18]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Leflunomide and Valganciclovir.	Virus infection [1A24-1D9Z]	[17]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Leflunomide 20 mg tablet	20 mg	Oral Tablet	Oral
Leflunomide 10 mg tablet	10 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6825).
• [2] Leflunomide FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 077090.
• [4] ClinicalTrials.gov (NCT04361214) Leflunomide in Mild COVID-19 Patients. U.S. National Institutes of Health.
• [5] BDDCS applied to over 900 drugs
• [6] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [7] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [8] Identification and characterization of potential new therapeutic targets in inflammatory and autoimmune diseases. Eur J Biochem. 1999 Dec;266(3):1184-91.
• [9] On dihydroorotate dehydrogenases and their inhibitors and uses. J Med Chem. 2013 Apr 25;56(8):3148-67. doi: 10.1021/jm301848w.
• [10] Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis. 2009 Jul;68(7):1201-7.
• [11] Prediction of drug-induced liver injury in HepG2 cells cultured with human liver microsomes. Chem Res Toxicol. 2015 May 18;28(5):872-85.
• [12] Leflunomide-induced acute hepatitis. Dig Liver Dis. 2004 Jan;36(1):82-4.
• [13] Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] EMEA "EMEA public statement on leflunomide (ARAVA) - severe and serious hepatic reactions.".
• [16] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [17] Cerner Multum, Inc. "Australian Product Information.".
• [18] Canadian Pharmacists Association.
• [19] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [20] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [21] Chonlahan J, Halloran MA, Hammonds A "Leflunomide and warfarin interaction: case report and review of the literature." Pharmacotherapy 26 (2006): 868-71. [PMID: 16716139]
• [22] Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [23] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [24] Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
• [25] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]