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Identification
NameLeflunomide
Accession NumberDB01097  (APRD00205)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionLeflunomide is a pyrimidine synthesis inhibitor belonging to the DMARD (disease-modifying antirheumatic drug) class of drugs, which are chemically and pharmacologically very heterogeneous. Leflunomide was approved by FDA and in many other countries (e.g., Canada, Europe) in 1999.
Structure
Thumb
Synonyms
5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide
5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide
alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-P-toluidide
Arava
Leflunomida
Leflunomide
Leflunomidum
Lefunomide
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AravaTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated10 mg/1OralSanofi Aventis U.S. Llc1998-09-10Not applicableUs
AravaTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated20 mg/1OralSanofi Aventis U.S. Llc1998-09-10Not applicableUs
AravaTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated20 mg/1Oralbryant ranch prepack1998-09-10Not applicableUs
AravaTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated100 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated100 mg/1OralSanofi Aventis U.S. Llc1998-09-19Not applicableUs
AravaTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
Arava 100 mgTablet100 mgOralSanofi Aventis Canada Inc2000-03-29Not applicableCanada
Arava 10mgTablet10 mgOralSanofi Aventis Canada Inc2000-03-29Not applicableCanada
Arava 20 mgTablet20 mgOralSanofi Aventis Canada Inc2000-03-29Not applicableCanada
Dom-leflunomideTablet10 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-leflunomideTablet20 mgOralDominion PharmacalNot applicableNot applicableCanada
LeflunomideTablet, film coated20 mg/1OralPrasco LLC1998-09-10Not applicableUs
LeflunomideTablet20 mgOralSanis Health Inc2010-06-15Not applicableCanada
LeflunomideTablet20 mgOralPro Doc Limitee2013-11-28Not applicableCanada
LeflunomideTablet, film coated20 mg/1OralWinthrop U.S.2015-09-07Not applicableUs
LeflunomideTablet, film coated10 mg/1OralPrasco LLC1998-09-10Not applicableUs
LeflunomideTablet10 mgOralSanis Health Inc2010-06-15Not applicableCanada
LeflunomideTablet, film coated10 mg/1OralWinthrop U.S.2015-09-07Not applicableUs
LeflunomideTablet10 mgOralPro Doc Limitee2013-11-28Not applicableCanada
Leflunomide WinthropTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated100 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated20 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropTablet, film coated10 mgOralSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Mylan-leflunomideTablet10 mgOralMylan Pharmaceuticals Ulc2008-11-14Not applicableCanada
Mylan-leflunomideTablet20 mgOralMylan Pharmaceuticals Ulc2008-11-14Not applicableCanada
Ntp-leflunomideTablet10 mgOralTeva Canada LimitedNot applicableNot applicableCanada
Ntp-leflunomideTablet20 mgOralTeva Canada LimitedNot applicableNot applicableCanada
Nu-leflunomideTablet20 mgOralNu Pharm IncNot applicableNot applicableCanada
Nu-leflunomideTablet10 mgOralNu Pharm IncNot applicableNot applicableCanada
PHL-leflunomideTablet10 mgOralPharmel Inc2008-10-31Not applicableCanada
PHL-leflunomideTablet20 mgOralPharmel Inc2008-10-31Not applicableCanada
PMS-leflunomideTablet10 mgOralPharmascience Inc2006-12-01Not applicableCanada
PMS-leflunomideTablet20 mgOralPharmascience Inc2006-12-01Not applicableCanada
Sandoz LeflunomideTablet10 mgOralSandoz Canada Incorporated2006-08-15Not applicableCanada
Sandoz LeflunomideTablet20 mgOralSandoz Canada Incorporated2006-08-15Not applicableCanada
Teva-leflunomideTablet10 mgOralTeva Canada Limited2004-12-21Not applicableCanada
Teva-leflunomideTablet20 mgOralTeva Canada Limited2004-12-21Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-leflunomideTablet10 mgOralApotex Inc2004-09-14Not applicableCanada
Apo-leflunomideTablet20 mgOralApotex Inc2004-09-14Not applicableCanada
LeflunomideTablet20 mg/1OralGolden State Medical Supply, Inc.2005-09-13Not applicableUs
LeflunomideTablet10 mg/1OralNorth Star Rx Llc2011-05-06Not applicableUs
LeflunomideTablet, film coated20 mg/1OralTeva Pharmaceuticals USA Inc2005-09-142015-10-31Us
LeflunomideTablet10 mg/1OralApotex Corp.2005-09-13Not applicableUs
LeflunomideTablet, film coated20 mg/1OralPhysicians Total Care, Inc.2006-07-10Not applicableUs
LeflunomideTablet20 mg/1OralDispensing Solutions, Inc.2009-10-29Not applicableUs
LeflunomideTablet20 mg/1OralNorth Star Rx Llc2011-05-06Not applicableUs
LeflunomideTablet20 mg/1OralApotex Corp.2005-09-13Not applicableUs
LeflunomideTablet, film coated10 mg/1OralPhysicians Total Care, Inc.2010-09-17Not applicableUs
LeflunomideTablet20 mg/1OralAvera Mc Kennan Hospital2015-03-01Not applicableUs
LeflunomideTablet10 mg/1OralHeritage Pharmaceuticals Inc2009-10-29Not applicableUs
LeflunomideTablet10 mg/1OralTrigen Laboratories, LLC2011-05-06Not applicableUs
LeflunomideTablet10 mg/1OralGolden State Medical Supply, Inc.2005-09-13Not applicableUs
LeflunomideTablet, film coated10 mg/1OralTeva Pharmaceuticals USA Inc2005-09-142015-10-31Us
LeflunomideTablet20 mg/1OralHeritage Pharmaceuticals Inc2009-10-29Not applicableUs
LeflunomideTablet20 mg/1OralTrigen Laboratories, LLC2011-05-06Not applicableUs
Leflunomide MedacTablet, film coated20 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated10 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated15 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated20 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated15 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated10 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated20 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated15 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated10 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated20 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated15 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated20 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacTablet, film coated10 mgOralMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide RatiopharmTablet, film coated10 mgOralRatiopharm Gmb H2010-11-29Not applicableEu
Leflunomide RatiopharmTablet, film coated10 mgOralRatiopharm Gmb H2010-11-29Not applicableEu
Leflunomide RatiopharmTablet, film coated20 mgOralRatiopharm Gmb H2010-11-29Not applicableEu
Leflunomide RatiopharmTablet, film coated20 mgOralRatiopharm Gmb H2010-11-29Not applicableEu
RepsoTablet, film coated10 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated20 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated10 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated10 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated20 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated20 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated10 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated20 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated20 mgOralTeva B.V.2011-03-14Not applicableEu
RepsoTablet, film coated10 mgOralTeva B.V.2011-03-14Not applicableEu
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Leflunomide TevaTablet, film coated20 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated10 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated10 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated20 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated10 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated20 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated20 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated10 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated20 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaTablet, film coated10 mgOralTeva Pharma B.V.2011-03-10Not applicableEu
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIG162GK9U4W
CAS number75706-12-6
WeightAverage: 270.2073
Monoisotopic: 270.061612157
Chemical FormulaC12H9F3N2O2
InChI KeyVHOGYURTWQBHIL-UHFFFAOYSA-N
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)
IUPAC Name
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
SMILES
CC1=C(C=NO1)C(=O)NC1=CC=C(C=C1)C(F)(F)F
Pharmacology
IndicationFor the management of the signs and symptoms of active rheumatoid arthritis (RA) to improve physical function and to slow the progression of structural damage associated with the disease. Has also been used for the prevention of acute and chronic rejection in recipients of solid organ trasnplants and is designated by the FDA as an orphan drug for this use.
Structured Indications
PharmacodynamicsLeflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.
Mechanism of actionLeflunomide is a prodrug that is rapidly and almost completely metabolized following oral administration to its pharmacologically active metabolite, A77 1726. This metabolite is responsible for essentially all of the drug's activity in-vivo. The mechanism of action of leflunomide has not been fully determined, but appears to primarily involve regulation of autoimmune lymphocytes. It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interferences with cell cycle progression. In-vitro data indicates that leflunomide interferes with cell cycle progression by inhibiting dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine ribonucleotide uridine monophosphate (rUMP)synthesis) and has antiproliferative activity. Human dihydroorotate dehydrogenase consists of 2 domains: an α/β-barrel domain containing the active site and an α-helical domain that forms a tunnel leading to the active site. A77 1726 binds to the hydrophobic tunnel at a site near the flavin mononucleotide. Inhibition of dihydroorotate dehydrogenase by A77 1726 prevents production of rUMP by the de novo pathway; such inhibition leads to decreased rUMP levels, decreased DNA and RNA synthesis, inhibition of cell proliferation, and G1 cell cycle arrest. It is through this action that leflunomide inhibits autoimmune T-cell proliferation and production of autoantibodies by B cells. Since salvage pathways are expected to sustain cells arrested in the G1 phase, the activity of leflunomide is cytostatic rather than cytotoxic. Other effects that result from reduced rUMP levels include interference with adhesion of activated lymphocytes to the synovial vascular endothelial cells, and increased synthesis of immunosuppressive cytokines such as transforming growth factor-β (TGF-β). Leflunomide is also a tyrosine kinase inhibitor. Tyrosine kinases activate signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of tyrosine kinases can help to treating cancer by preventing repair of tumor cells.
TargetKindPharmacological actionActionsOrganismUniProt ID
Dihydroorotate dehydrogenase (quinone), mitochondrialProteinyes
inhibitor
HumanQ02127 details
Aryl hydrocarbon receptorProteinunknown
agonist
HumanP35869 details
Protein-tyrosine kinase 2-betaProteinunknown
antagonist
HumanQ14289 details
Related Articles
AbsorptionWell absorbed, peak plasma concentrations appear 6-12 hours after dosing
Volume of distribution
  • 0.13 L/kg
Protein binding>99.3%
Metabolism

Primarily hepatic. Leflunomide is converted to its active form following oral intake.

SubstrateEnzymesProduct
Leflunomide
A771726Details
Route of eliminationThe active metabolite is eliminated by further metabolism and subsequent renal excretion as well as by direct biliary excretion. In a 28 day study of drug elimination (n=3) using a single dose of radiolabeled compound, approximately 43% of the total radioactivity was eliminated in the urine and 48% was eliminated in the feces. It is not known whether leflunomide is excreted in human milk. Many drugs are excreted in human milk, and there is a potential for serious adverse reactions in nursing infants from leflunomide.
Half life2 weeks
ClearanceNot Available
ToxicityLD50=100-250 mg/kg (acute oral toxicity)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Cytochrome P450 1A2
Gene symbol: CYP1A2
UniProt: P05177
rs762551 Not AvailableC alleleDiarrhea, vomiting, liver toxicity, headache, insomnia, rash, alopecia, hypertension, leucopenia, asthma18496682
Interactions
Drug Interactions
DrugInteractionDrug group
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Leflunomide is combined with 16-Bromoepiandrosterone.Investigational
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Leflunomide is combined with 19-norandrostenedione.Experimental, Illicit
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Leflunomide.Experimental
4-AndrostenedioneThe risk or severity of adverse effects can be increased when Leflunomide is combined with 4-Androstenedione.Experimental, Illicit
5-androstenedioneThe risk or severity of adverse effects can be increased when Leflunomide is combined with 5-androstenedione.Experimental, Illicit
9-(2-phosphonylmethoxyethyl)-2,6-diaminopurineThe risk or severity of adverse effects can be increased when 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine is combined with Leflunomide.Investigational
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Leflunomide.Approved
AbciximabLeflunomide may increase the anticoagulant activities of Abciximab.Approved
abetimusThe risk or severity of adverse effects can be increased when abetimus is combined with Leflunomide.Investigational
AbirateroneThe serum concentration of Leflunomide can be increased when it is combined with Abiraterone.Approved
ABR-215757The risk or severity of adverse effects can be increased when ABR-215757 is combined with Leflunomide.Investigational
AcebutololLeflunomide may decrease the antihypertensive activities of Acebutolol.Approved
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Leflunomide.Approved
AcenocoumarolLeflunomide may increase the anticoagulant activities of Acenocoumarol.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Leflunomide.Approved
AcetovanilloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Acetovanillone.Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Leflunomide.Approved
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Leflunomide.Approved, Vet Approved
AclarubicinLeflunomide may decrease the excretion rate of Aclarubicin which could result in a higher serum level.Investigational
ActeosideThe risk or severity of adverse effects can be increased when Acteoside is combined with Leflunomide.Investigational
Activated charcoalThe serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Activated charcoal resulting in a loss in efficacy.Approved
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Leflunomide.Approved
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Leflunomide.Approved
Adefovir DipivoxilThe risk or severity of adverse effects can be increased when Adefovir Dipivoxil is combined with Leflunomide.Approved, Investigational
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Leflunomide.Investigational
AlclometasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Alclometasone.Approved
AldosteroneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Aldosterone.Experimental
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Leflunomide.Approved, Withdrawn
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Leflunomide.Approved, Investigational
Alendronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Alendronic acid.Approved
alicaforsenThe risk or severity of adverse effects can be increased when alicaforsen is combined with Leflunomide.Investigational
AliskirenLeflunomide may decrease the antihypertensive activities of Aliskiren.Approved, Investigational
AlosetronThe metabolism of Alosetron can be decreased when combined with Leflunomide.Approved, Withdrawn
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Leflunomide.Approved, Illicit, Investigational
AlprenololLeflunomide may decrease the antihypertensive activities of Alprenolol.Approved, Withdrawn
AlprostadilThe therapeutic efficacy of Alprostadil can be decreased when used in combination with Leflunomide.Approved, Investigational
ALT-110The risk or severity of adverse effects can be increased when Leflunomide is combined with ALT-110.Investigational
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.Approved
AmcinonideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Amcinonide.Approved
Amg 827The risk or severity of adverse effects can be increased when Amg 827 is combined with Leflunomide.Investigational
AmikacinLeflunomide may decrease the excretion rate of Amikacin which could result in a higher serum level.Approved, Vet Approved
AmilorideLeflunomide may decrease the antihypertensive activities of Amiloride.Approved
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Leflunomide.Approved, Withdrawn
AmiodaroneThe metabolism of Leflunomide can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Leflunomide.Approved
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Leflunomide.Approved
AmrubicinLeflunomide may decrease the excretion rate of Amrubicin which could result in a higher serum level.Approved, Investigational
AmsacrineThe risk or severity of adverse effects can be increased when Amsacrine is combined with Leflunomide.Approved
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide.Approved
AncrodLeflunomide may increase the anticoagulant activities of Ancrod.Investigational
AnecortaveThe risk or severity of adverse effects can be increased when Leflunomide is combined with Anecortave.Investigational
AnisodamineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Anisodamine.Investigational
annamycinLeflunomide may decrease the excretion rate of annamycin which could result in a higher serum level.Investigational
Anti-thymocyte Globulin (Rabbit)The risk or severity of adverse effects can be increased when Anti-thymocyte Globulin (Rabbit) is combined with Leflunomide.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Leflunomide.Approved
Antithrombin III humanLeflunomide may increase the anticoagulant activities of Antithrombin III human.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Leflunomide.Investigational
Aop200704Leflunomide may decrease the antihypertensive activities of Aop200704.Investigational
ApixabanThe metabolism of Apixaban can be decreased when combined with Leflunomide.Approved
ApramycinLeflunomide may decrease the excretion rate of Apramycin which could result in a higher serum level.Experimental, Vet Approved
ApremilastThe risk or severity of adverse effects can be increased when Apremilast is combined with Leflunomide.Approved, Investigational
AprepitantThe metabolism of Leflunomide can be increased when combined with Aprepitant.Approved, Investigational
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Leflunomide.Experimental
ArbekacinLeflunomide may decrease the excretion rate of Arbekacin which could result in a higher serum level.Approved
ArdeparinLeflunomide may increase the anticoagulant activities of Ardeparin.Approved, Withdrawn
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Leflunomide.Approved, Investigational
ArgatrobanLeflunomide may increase the anticoagulant activities of Argatroban.Approved, Investigational
ArotinololLeflunomide may decrease the antihypertensive activities of Arotinolol.Approved
ArtemetherThe metabolism of Artemether can be decreased when combined with Leflunomide.Approved
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Leflunomide.Approved, Investigational
AtenololLeflunomide may decrease the antihypertensive activities of Atenolol.Approved
AzacitidineThe risk or severity of adverse effects can be increased when Azacitidine is combined with Leflunomide.Approved, Investigational
AzapropazoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Azapropazone.Withdrawn
AzathioprineThe risk or severity of adverse effects can be increased when Azathioprine is combined with Leflunomide.Approved
AzelastineThe metabolism of Azelastine can be decreased when combined with Leflunomide.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Leflunomide.Approved
AzithromycinThe metabolism of Leflunomide can be decreased when combined with Azithromycin.Approved
BalsalazideLeflunomide may increase the nephrotoxic activities of Balsalazide.Approved, Investigational
BasiliximabThe risk or severity of adverse effects can be increased when Basiliximab is combined with Leflunomide.Approved, Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Leflunomide.Investigational
BecaplerminLeflunomide may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BeclomethasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Beclomethasone.Investigational
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Beclomethasone dipropionate.Approved, Investigational
BefunololLeflunomide may decrease the antihypertensive activities of Befunolol.Experimental
BelataceptThe risk or severity of adverse effects can be increased when Belatacept is combined with Leflunomide.Approved
BelimumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Leflunomide.Approved
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Leflunomide.Approved, Investigational
BendroflumethiazideThe therapeutic efficacy of Bendroflumethiazide can be decreased when used in combination with Leflunomide.Approved
BenoxaprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Benoxaprofen.Withdrawn
BenznidazoleThe risk or severity of adverse effects can be increased when Benznidazole is combined with Leflunomide.Investigational
BeraprostThe therapeutic efficacy of Beraprost can be decreased when used in combination with Leflunomide.Investigational
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Leflunomide.Approved, Vet Approved
BetaxololLeflunomide may decrease the antihypertensive activities of Betaxolol.Approved
Betulinic AcidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Betulinic Acid.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Leflunomide.Approved, Investigational
BevantololLeflunomide may decrease the antihypertensive activities of Bevantolol.Approved
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Leflunomide.Approved, Investigational
BimatoprostThe therapeutic efficacy of Bimatoprost can be decreased when used in combination with Leflunomide.Approved, Investigational
BisoprololLeflunomide may decrease the antihypertensive activities of Bisoprolol.Approved
BivalirudinLeflunomide may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BleomycinThe risk or severity of adverse effects can be increased when Bleomycin is combined with Leflunomide.Approved
BlinatumomabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.Approved
BopindololLeflunomide may decrease the antihypertensive activities of Bopindolol.Approved
BortezomibThe metabolism of Leflunomide can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Bosentan can be increased when it is combined with Leflunomide.Approved, Investigational
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Leflunomide.Approved
BriakinumabThe risk or severity of adverse effects can be increased when Briakinumab is combined with Leflunomide.Investigational
BromfenacThe risk or severity of adverse effects can be increased when Bromfenac is combined with Leflunomide.Approved
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Leflunomide.Approved
BucillamineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Bucillamine.Investigational
BucindololLeflunomide may decrease the antihypertensive activities of Bucindolol.Investigational
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Leflunomide.Approved
BufuralolLeflunomide may decrease the antihypertensive activities of Bufuralol.Experimental, Investigational
BumetanideLeflunomide may decrease the diuretic activities of Bumetanide.Approved
BupranololLeflunomide may decrease the antihypertensive activities of Bupranolol.Approved
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Leflunomide.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Bupropion can be decreased when combined with Leflunomide.Approved
BusulfanThe risk or severity of adverse effects can be increased when Busulfan is combined with Leflunomide.Approved, Investigational
C1 Esterase Inhibitor (Human)The risk or severity of adverse effects can be increased when C1 Esterase Inhibitor (Human) is combined with Leflunomide.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Leflunomide.Approved
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Leflunomide.Approved
CaffeineThe metabolism of Leflunomide can be decreased when combined with Caffeine.Approved
CanakinumabThe risk or severity of adverse effects can be increased when Canakinumab is combined with Leflunomide.Approved, Investigational
CandesartanThe metabolism of Candesartan can be decreased when combined with Leflunomide.Approved
CandoxatrilThe risk or severity of adverse effects can be increased when Candoxatril is combined with Leflunomide.Experimental
CapecitabineThe risk or severity of adverse effects can be increased when Capecitabine is combined with Leflunomide.Approved, Investigational
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Leflunomide.Approved
CarbamazepineThe metabolism of Leflunomide can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Leflunomide.Approved
CarboplatinThe risk or severity of adverse effects can be increased when Carboplatin is combined with Leflunomide.Approved
Carboprost TromethamineThe therapeutic efficacy of Carboprost Tromethamine can be decreased when used in combination with Leflunomide.Approved
CarmustineThe risk or severity of adverse effects can be increased when Carmustine is combined with Leflunomide.Approved
CarprofenThe risk or severity of adverse effects can be increased when Carprofen is combined with Leflunomide.Approved, Vet Approved, Withdrawn
CarteololLeflunomide may decrease the antihypertensive activities of Carteolol.Approved
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Leflunomide.Approved, Investigational
CastanospermineThe risk or severity of adverse effects can be increased when Castanospermine is combined with Leflunomide.Experimental
CDX-110The risk or severity of adverse effects can be increased when Leflunomide is combined with CDX-110.Investigational
CelecoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Celecoxib.Approved, Investigational
CeliprololLeflunomide may decrease the antihypertensive activities of Celiprolol.Approved, Investigational
CeritinibThe serum concentration of Leflunomide can be increased when it is combined with Ceritinib.Approved
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Leflunomide.Approved
CertoparinLeflunomide may increase the anticoagulant activities of Certoparin.Approved
ChlorambucilThe risk or severity of adverse effects can be increased when Chlorambucil is combined with Leflunomide.Approved
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Leflunomide.Approved, Vet Approved
ChlorothiazideThe therapeutic efficacy of Chlorothiazide can be decreased when used in combination with Leflunomide.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Leflunomide.Approved
ChlorthalidoneThe therapeutic efficacy of Chlorthalidone can be decreased when used in combination with Leflunomide.Approved
CholecalciferolThe metabolism of Leflunomide can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CholestyramineThe serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Cholestyramine resulting in a loss in efficacy.Approved
CiclesonideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ciclesonide.Approved, Investigational
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Leflunomide.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Leflunomide.Approved
CinoxacinLeflunomide may increase the neuroexcitatory activities of Cinoxacin.Approved, Withdrawn
CiprofloxacinLeflunomide may increase the neuroexcitatory activities of Ciprofloxacin.Approved, Investigational
CisaprideThe metabolism of Cisapride can be decreased when combined with Leflunomide.Approved, Investigational, Withdrawn
CisplatinThe risk or severity of adverse effects can be increased when Cisplatin is combined with Leflunomide.Approved
CitalopramThe metabolism of Leflunomide can be decreased when combined with Citalopram.Approved
Citric AcidLeflunomide may increase the anticoagulant activities of Citric Acid.Nutraceutical, Vet Approved
CladribineThe risk or severity of adverse effects can be increased when Cladribine is combined with Leflunomide.Approved, Investigational
ClobetasolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasol.Investigational
Clobetasol propionateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasol propionate.Approved
ClocortoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clocortolone.Approved
ClodronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clodronate.Approved, Investigational, Vet Approved
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Leflunomide.Approved, Investigational
ClonixinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clonixin.Approved
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Leflunomide.Approved, Nutraceutical
CloprostenolThe therapeutic efficacy of Cloprostenol can be decreased when used in combination with Leflunomide.Vet Approved
ClotrimazoleThe metabolism of Leflunomide can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Clozapine can be decreased when combined with Leflunomide.Approved
ColesevelamThe serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Colesevelam resulting in a loss in efficacy.Approved
ColestipolThe serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Colestipol resulting in a loss in efficacy.Approved
CorticotropinThe risk or severity of adverse effects can be increased when Corticotropin is combined with Leflunomide.Approved, Vet Approved
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Leflunomide.Approved
CurcuminThe risk or severity of adverse effects can be increased when Leflunomide is combined with Curcumin.Investigational
CyclophosphamideThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Leflunomide.Approved, Investigational
CyclosporineThe risk or severity of adverse effects can be increased when Cyclosporine is combined with Leflunomide.Approved, Investigational, Vet Approved
CyclosporineLeflunomide may increase the nephrotoxic activities of Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Leflunomide can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
CytarabineThe risk or severity of adverse effects can be increased when Cytarabine is combined with Leflunomide.Approved, Investigational
D-LimoneneThe risk or severity of adverse effects can be increased when Leflunomide is combined with D-Limonene.Investigational
Dabigatran etexilateLeflunomide may increase the anticoagulant activities of Dabigatran etexilate.Approved
DabrafenibThe serum concentration of Leflunomide can be decreased when it is combined with Dabrafenib.Approved
DacarbazineThe risk or severity of adverse effects can be increased when Dacarbazine is combined with Leflunomide.Approved, Investigational
DaclizumabThe risk or severity of adverse effects can be increased when Daclizumab is combined with Leflunomide.Approved, Investigational
DactinomycinThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Leflunomide.Approved
DalteparinLeflunomide may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidLeflunomide may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Leflunomide.Approved
DapsoneThe metabolism of Dapsone can be decreased when combined with Leflunomide.Approved, Investigational
DasatinibThe risk or severity of adverse effects can be increased when Dasatinib is combined with Leflunomide.Approved, Investigational
DaunorubicinThe risk or severity of adverse effects can be increased when Daunorubicin is combined with Leflunomide.Approved
DeferasiroxThe risk or severity of adverse effects can be increased when Leflunomide is combined with Deferasirox.Approved, Investigational
dehydroepiandrosterone sulfateThe risk or severity of adverse effects can be increased when Leflunomide is combined with dehydroepiandrosterone sulfate.Investigational
DelavirdineThe metabolism of Leflunomide can be decreased when combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Leflunomide.Approved
DeoxyspergualinThe risk or severity of adverse effects can be increased when Deoxyspergualin is combined with Leflunomide.Investigational
DesirudinLeflunomide may increase the anticoagulant activities of Desirudin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Leflunomide.Approved
DesmopressinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Desmopressin.Approved
DesoximetasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Desoximetasone.Approved
Desoxycorticosterone acetateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Desoxycorticosterone acetate.Approved
Desoxycorticosterone PivalateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Desoxycorticosterone Pivalate.Experimental, Vet Approved
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Leflunomide.Approved, Investigational, Vet Approved
Dexamethasone isonicotinateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Dexamethasone isonicotinate.Vet Approved
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Leflunomide.Approved
DextranLeflunomide may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Leflunomide may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Leflunomide may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Leflunomide may increase the anticoagulant activities of Dextran 75.Approved
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Leflunomide.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Leflunomide.Approved, Illicit, Vet Approved
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Leflunomide.Approved, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Leflunomide.Approved, Vet Approved
DicoumarolLeflunomide may increase the anticoagulant activities of Dicoumarol.Approved
DiflorasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Diflorasone.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Leflunomide.Approved
DifluocortoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Difluocortolone.Approved
DifluprednateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Difluprednate.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Leflunomide.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Leflunomide.Approved
DihydrostreptomycinLeflunomide may decrease the excretion rate of Dihydrostreptomycin which could result in a higher serum level.Vet Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Leflunomide.Approved
Dimethyl fumarateThe risk or severity of adverse effects can be increased when Dimethyl fumarate is combined with Leflunomide.Approved, Investigational
DinoprostThe therapeutic efficacy of Dinoprost can be decreased when used in combination with Leflunomide.Investigational
Dinoprost TromethamineThe therapeutic efficacy of Dinoprost Tromethamine can be decreased when used in combination with Leflunomide.Approved, Vet Approved
DinoprostoneThe therapeutic efficacy of Dinoprostone can be decreased when used in combination with Leflunomide.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Leflunomide.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Leflunomide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Leflunomide.Approved, Investigational
DolasetronThe metabolism of Dolasetron can be decreased when combined with Leflunomide.Approved
DonepezilThe metabolism of Donepezil can be decreased when combined with Leflunomide.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Leflunomide.Approved
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Leflunomide.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Leflunomide.Approved
DoxifluridineThe risk or severity of adverse effects can be increased when Doxifluridine is combined with Leflunomide.Investigational
DoxorubicinThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Leflunomide.Approved, Investigational
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Leflunomide.Approved, Illicit
DrospirenoneLeflunomide may increase the hyperkalemic activities of Drospirenone.Approved
DroxicamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Droxicam.Approved
DuvelisibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Duvelisib.Investigational
E6201The risk or severity of adverse effects can be increased when Leflunomide is combined with E6201.Investigational
EbselenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ebselen.Investigational
EculizumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Leflunomide.Approved, Investigational
Edetic AcidLeflunomide may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanLeflunomide may increase the anticoagulant activities of Edoxaban.Approved
EfalizumabThe risk or severity of adverse effects can be increased when Efalizumab is combined with Leflunomide.Approved, Investigational
EfavirenzThe metabolism of Leflunomide can be decreased when combined with Efavirenz.Approved, Investigational
EletriptanThe metabolism of Eletriptan can be decreased when combined with Leflunomide.Approved, Investigational
EltrombopagThe serum concentration of Leflunomide can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Leflunomide.Approved, Vet Approved
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Leflunomide.Approved
EnoxacinLeflunomide may increase the neuroexcitatory activities of Enoxacin.Approved
EnoxaparinLeflunomide may increase the anticoagulant activities of Enoxaparin.Approved
EpirizoleThe risk or severity of adverse effects can be increased when Leflunomide is combined with Epirizole.Approved
EpirubicinThe risk or severity of adverse effects can be increased when Epirubicin is combined with Leflunomide.Approved
EplerenoneLeflunomide may decrease the antihypertensive activities of Eplerenone.Approved
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Leflunomide.Approved
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Leflunomide.Approved
EquileninThe risk or severity of adverse effects can be increased when Leflunomide is combined with Equilenin.Experimental
EquilinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Equilin.Approved
EsmololLeflunomide may decrease the antihypertensive activities of Esmolol.Approved
EstradiolThe metabolism of Estradiol can be decreased when combined with Leflunomide.Approved, Investigational, Vet Approved
EstramustineThe risk or severity of adverse effects can be increased when Estramustine is combined with Leflunomide.Approved
EstroneThe metabolism of Estrone can be decreased when combined with Leflunomide.Approved
Estrone sulfateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Estrone sulfate.Approved
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Leflunomide.Approved
Etacrynic acidLeflunomide may decrease the diuretic activities of Etacrynic acid.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Leflunomide.Approved, Investigational
Ethyl biscoumacetateLeflunomide may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Etidronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etidronic acid.Approved
EtodolacThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etodolac.Approved, Investigational, Vet Approved
EtofenamateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etofenamate.Approved
EtoposideThe risk or severity of adverse effects can be increased when Etoposide is combined with Leflunomide.Approved
EtoricoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etoricoxib.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Leflunomide.Approved
Evening primrose oilThe risk or severity of adverse effects can be increased when Leflunomide is combined with Evening primrose oil.Approved
EverolimusThe risk or severity of adverse effects can be increased when Everolimus is combined with Leflunomide.Approved
exisulindThe risk or severity of adverse effects can be increased when Leflunomide is combined with exisulind.Investigational
FenbufenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fenbufen.Approved
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Leflunomide.Approved
FenprostaleneThe therapeutic efficacy of Fenprostalene can be decreased when used in combination with Leflunomide.Vet Approved
FingolimodThe risk or severity of adverse effects can be increased when Fingolimod is combined with Leflunomide.Approved, Investigational
FleroxacinLeflunomide may increase the neuroexcitatory activities of Fleroxacin.Approved
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Leflunomide.Approved, Withdrawn
FloxuridineThe risk or severity of adverse effects can be increased when Floxuridine is combined with Leflunomide.Approved
fluasteroneThe risk or severity of adverse effects can be increased when Leflunomide is combined with fluasterone.Investigational
FluconazoleThe metabolism of Leflunomide can be decreased when combined with Fluconazole.Approved
FludarabineThe risk or severity of adverse effects can be increased when Fludarabine is combined with Leflunomide.Approved
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Leflunomide.Approved
FluindioneLeflunomide may increase the anticoagulant activities of Fluindione.Investigational
FlumequineLeflunomide may increase the neuroexcitatory activities of Flumequine.Withdrawn
FlumethasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Flumethasone.Approved, Vet Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Leflunomide.Approved
FlunisolideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Flunisolide.Approved, Investigational
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Leflunomide.Approved, Illicit
FlunixinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Flunixin.Vet Approved
Fluocinolone AcetonideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocinolone Acetonide.Approved, Investigational, Vet Approved
FluocinonideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocinonide.Approved, Investigational
FluocortoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocortolone.Approved, Withdrawn
FluorometholoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluorometholone.Approved
FluorouracilThe risk or severity of adverse effects can be increased when Fluorouracil is combined with Leflunomide.Approved
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Leflunomide.Approved, Vet Approved
FluprednideneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluprednidene.Approved, Withdrawn
FluprednisoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluprednisolone.Approved
FluprostenolThe therapeutic efficacy of Fluprostenol can be decreased when used in combination with Leflunomide.Vet Approved
FlurandrenolideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Flurandrenolide.Approved
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Leflunomide.Approved, Investigational
Fluticasone furoateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluticasone furoate.Approved
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fluticasone Propionate.Approved
FluvastatinThe metabolism of Leflunomide can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Leflunomide can be decreased when combined with Fluvoxamine.Approved, Investigational
Folic AcidThe therapeutic efficacy of Folic Acid can be decreased when used in combination with Leflunomide.Approved, Nutraceutical, Vet Approved
FondaparinuxLeflunomide may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumLeflunomide may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
ForasartanThe risk or severity of adverse effects can be increased when Forasartan is combined with Leflunomide.Experimental
FormestaneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Formestane.Approved, Investigational, Withdrawn
FormoterolThe metabolism of Formoterol can be decreased when combined with Leflunomide.Approved, Investigational
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Leflunomide.Approved
FosphenytoinThe metabolism of Leflunomide can be increased when combined with Fosphenytoin.Approved
FramycetinLeflunomide may decrease the excretion rate of Framycetin which could result in a higher serum level.Approved
FurosemideLeflunomide may decrease the diuretic activities of Furosemide.Approved, Vet Approved
G17DTThe risk or severity of adverse effects can be increased when Leflunomide is combined with G17DT.Investigational
GabexateLeflunomide may increase the anticoagulant activities of Gabexate.Investigational
Gallium nitrateThe risk or severity of adverse effects can be increased when Gallium nitrate is combined with Leflunomide.Approved, Investigational
GarenoxacinLeflunomide may increase the neuroexcitatory activities of Garenoxacin.Investigational
GatifloxacinLeflunomide may increase the neuroexcitatory activities of Gatifloxacin.Approved, Investigational
GavestinelThe metabolism of Gavestinel can be decreased when combined with Leflunomide.Investigational
GemcitabineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Leflunomide.Approved
GemeprostThe therapeutic efficacy of Gemeprost can be decreased when used in combination with Leflunomide.Approved, Withdrawn
GemfibrozilThe metabolism of Leflunomide can be decreased when combined with Gemfibrozil.Approved
GemifloxacinLeflunomide may increase the neuroexcitatory activities of Gemifloxacin.Approved, Investigational
Gemtuzumab ozogamicinThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Leflunomide.Approved, Investigational, Withdrawn
GeneticinLeflunomide may decrease the excretion rate of Geneticin which could result in a higher serum level.Experimental
GentamicinLeflunomide may decrease the excretion rate of Gentamicin which could result in a higher serum level.Approved, Vet Approved
GENTAMICIN C1ALeflunomide may decrease the excretion rate of GENTAMICIN C1A which could result in a higher serum level.Experimental
GI-5005The risk or severity of adverse effects can be increased when Leflunomide is combined with GI-5005.Investigational
Glatiramer AcetateThe risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Leflunomide.Approved, Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Leflunomide.Approved
GlimepirideThe risk or severity of adverse effects can be increased when Glimepiride is combined with Leflunomide.Approved
GlipizideThe metabolism of Glipizide can be decreased when combined with Leflunomide.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Leflunomide.Approved
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Leflunomide.Approved
GrepafloxacinLeflunomide may increase the neuroexcitatory activities of Grepafloxacin.Withdrawn
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Leflunomide.Approved, Investigational
GusperimusThe risk or severity of adverse effects can be increased when Gusperimus is combined with Leflunomide.Investigational
HaloperidolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Haloperidol.Approved
HalothaneThe metabolism of Halothane can be decreased when combined with Leflunomide.Approved, Vet Approved
HE3286The risk or severity of adverse effects can be increased when Leflunomide is combined with HE3286.Investigational
HeparinLeflunomide may increase the anticoagulant activities of Heparin.Approved, Investigational
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Leflunomide.Approved
HigenamineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Higenamine.Investigational
HirulogLeflunomide may increase the anticoagulant activities of Hirulog.Experimental
Histamine PhosphateThe metabolism of Histamine Phosphate can be decreased when combined with Leflunomide.Approved
HMPL-004The risk or severity of adverse effects can be increased when Leflunomide is combined with HMPL-004.Investigational
HydralazineLeflunomide may decrease the antihypertensive activities of Hydralazine.Approved
HydrochlorothiazideThe therapeutic efficacy of Hydrochlorothiazide can be decreased when used in combination with Leflunomide.Approved, Vet Approved
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Leflunomide.Approved, Vet Approved
HydroflumethiazideThe therapeutic efficacy of Hydroflumethiazide can be decreased when used in combination with Leflunomide.Approved
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Leflunomide.Approved, Illicit
HydroxyureaThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Leflunomide.Approved
Hygromycin BLeflunomide may decrease the excretion rate of Hygromycin B which could result in a higher serum level.Vet Approved
IbandronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ibandronate.Approved, Investigational
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Leflunomide.Approved
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Leflunomide.Approved
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Leflunomide.Approved
IbuproxamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ibuproxam.Withdrawn
IcatibantThe risk or severity of adverse effects can be increased when Icatibant is combined with Leflunomide.Approved
IdarubicinThe risk or severity of adverse effects can be increased when Idarubicin is combined with Leflunomide.Approved
IdelalisibThe risk or severity of adverse effects can be increased when Idelalisib is combined with Leflunomide.Approved
idraparinuxLeflunomide may increase the anticoagulant activities of idraparinux.Investigational
IfosfamideThe risk or severity of adverse effects can be increased when Ifosfamide is combined with Leflunomide.Approved
IloprostThe therapeutic efficacy of Iloprost can be decreased when used in combination with Leflunomide.Approved, Investigational
ImatinibThe risk or severity of adverse effects can be increased when Imatinib is combined with Leflunomide.Approved
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Leflunomide.Investigational
ImiquimodThe risk or severity of adverse effects can be increased when Imiquimod is combined with Leflunomide.Approved, Investigational
IndapamideThe therapeutic efficacy of Indapamide can be decreased when used in combination with Leflunomide.Approved
IndenololLeflunomide may decrease the antihypertensive activities of Indenolol.Withdrawn
IndinavirThe metabolism of Leflunomide can be decreased when combined with Indinavir.Approved
indisulamThe metabolism of indisulam can be decreased when combined with Leflunomide.Investigational
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Leflunomide.Approved, Investigational
IndoprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Indoprofen.Withdrawn
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Leflunomide.Approved
INGN 201The risk or severity of adverse effects can be increased when Leflunomide is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Leflunomide is combined with INGN 225.Investigational
INNO-206Leflunomide may decrease the excretion rate of INNO-206 which could result in a higher serum level.Investigational
IrbesartanThe metabolism of Leflunomide can be decreased when combined with Irbesartan.Approved, Investigational
IrinotecanThe risk or severity of adverse effects can be increased when Irinotecan is combined with Leflunomide.Approved, Investigational
IsoxicamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Isoxicam.Withdrawn
IstaroximeThe risk or severity of adverse effects can be increased when Leflunomide is combined with Istaroxime.Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Leflunomide.Approved
KanamycinLeflunomide may decrease the excretion rate of Kanamycin which could result in a higher serum level.Approved, Vet Approved
KebuzoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Kebuzone.Experimental
KetamineThe metabolism of Ketamine can be decreased when combined with Leflunomide.Approved, Vet Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Leflunomide.Approved
KetoconazoleThe metabolism of Leflunomide can be decreased when combined with Ketoconazole.Approved, Investigational
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Leflunomide.Approved, Vet Approved
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Leflunomide.Approved
L-PhenylalanineThe risk or severity of adverse effects can be increased when L-Phenylalanine is combined with Leflunomide.Approved, Nutraceutical
LabetalolLeflunomide may decrease the antihypertensive activities of Labetalol.Approved
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Leflunomide.Approved, Investigational
LatanoprostThe therapeutic efficacy of Latanoprost can be decreased when used in combination with Leflunomide.Approved, Investigational
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Leflunomide.Approved
LepirudinLeflunomide may increase the anticoagulant activities of Lepirudin.Approved
LesinuradThe metabolism of Lesinurad can be decreased when combined with Leflunomide.Approved
LevobunololLeflunomide may decrease the antihypertensive activities of Levobunolol.Approved
LevofloxacinLeflunomide may increase the neuroexcitatory activities of Levofloxacin.Approved, Investigational
LicofeloneThe metabolism of Licofelone can be decreased when combined with Leflunomide.Investigational
LidocaineThe metabolism of Leflunomide can be decreased when combined with Lidocaine.Approved, Vet Approved
LimaprostThe therapeutic efficacy of Limaprost can be decreased when used in combination with Leflunomide.Approved
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Leflunomide.Approved, Investigational
LisofyllineThe risk or severity of adverse effects can be increased when Lisofylline is combined with Leflunomide.Investigational
LithiumThe serum concentration of Lithium can be increased when it is combined with Leflunomide.Approved
LomefloxacinLeflunomide may increase the neuroexcitatory activities of Lomefloxacin.Approved
LomustineThe risk or severity of adverse effects can be increased when Lomustine is combined with Leflunomide.Approved
LoratadineThe metabolism of Loratadine can be decreased when combined with Leflunomide.Approved
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Leflunomide.Approved
LosartanThe metabolism of Leflunomide can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Leflunomide can be decreased when combined with Lovastatin.Approved, Investigational
LoxoprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Loxoprofen.Approved
LubiprostoneThe therapeutic efficacy of Lubiprostone can be decreased when used in combination with Leflunomide.Approved, Investigational
LumacaftorThe serum concentration of Leflunomide can be decreased when it is combined with Lumacaftor.Approved
LumiracoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Lumiracoxib.Approved, Investigational
LuprostiolThe therapeutic efficacy of Luprostiol can be decreased when used in combination with Leflunomide.Vet Approved
Lx211The risk or severity of adverse effects can be increased when Lx211 is combined with Leflunomide.Investigational
Magnesium salicylateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Magnesium salicylate.Approved
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Leflunomide.Approved
ME-609The risk or severity of adverse effects can be increased when Leflunomide is combined with ME-609.Investigational
MechlorethamineThe risk or severity of adverse effects can be increased when Mechlorethamine is combined with Leflunomide.Approved
Meclofenamic acidThe risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Leflunomide.Approved, Vet Approved
MedrysoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Medrysone.Approved
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Leflunomide.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Leflunomide.Approved, Nutraceutical, Vet Approved
MelengestrolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Melengestrol.Vet Approved
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Leflunomide.Approved, Vet Approved
MelphalanThe risk or severity of adverse effects can be increased when Melphalan is combined with Leflunomide.Approved
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Leflunomide.Investigational, Withdrawn
MepolizumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Leflunomide.Approved, Investigational
MercaptopurineThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Leflunomide.Approved
MesalazineLeflunomide may increase the nephrotoxic activities of Mesalazine.Approved
MestranolThe metabolism of Mestranol can be decreased when combined with Leflunomide.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Leflunomide is combined with Metamizole.Withdrawn
MethadoneThe metabolism of Methadone can be decreased when combined with Leflunomide.Approved
MethotrexateThe risk or severity of adverse effects can be increased when Methotrexate is combined with Leflunomide.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Leflunomide.Approved, Vet Approved
MethyclothiazideThe therapeutic efficacy of Methyclothiazide can be decreased when used in combination with Leflunomide.Approved
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Leflunomide.Approved, Vet Approved
MetipranololLeflunomide may decrease the antihypertensive activities of Metipranolol.Approved
MetolazoneThe therapeutic efficacy of Metolazone can be decreased when used in combination with Leflunomide.Approved
MetoprololLeflunomide may decrease the antihypertensive activities of Metoprolol.Approved, Investigational
MetrizamideLeflunomide may decrease the excretion rate of Metrizamide which could result in a higher serum level.Approved
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Leflunomide.Approved
MexiletineThe metabolism of Leflunomide can be decreased when combined with Mexiletine.Approved
MifepristoneThe serum concentration of Leflunomide can be increased when it is combined with Mifepristone.Approved, Investigational
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Leflunomide.Approved
MisoprostolThe therapeutic efficacy of Misoprostol can be decreased when used in combination with Leflunomide.Approved
MitomycinThe risk or severity of adverse effects can be increased when Mitomycin is combined with Leflunomide.Approved
MitoxantroneThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with Leflunomide.Approved, Investigational
MizoribineThe risk or severity of adverse effects can be increased when Mizoribine is combined with Leflunomide.Investigational
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Leflunomide.Approved
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Leflunomide.Approved
MometasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Mometasone.Approved, Vet Approved
MontelukastThe metabolism of Montelukast can be decreased when combined with Leflunomide.Approved
MorniflumateThe risk or severity of adverse effects can be increased when Morniflumate is combined with Leflunomide.Approved
MoxifloxacinLeflunomide may increase the neuroexcitatory activities of Moxifloxacin.Approved, Investigational
MuromonabThe risk or severity of adverse effects can be increased when Muromonab is combined with Leflunomide.Approved, Investigational
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Leflunomide.Approved, Investigational
Mycophenolic acidThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Leflunomide.Approved
NabumetoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nabumetone.Approved
NadololLeflunomide may decrease the antihypertensive activities of Nadolol.Approved
NadroparinLeflunomide may increase the anticoagulant activities of Nadroparin.Approved
NafamostatThe risk or severity of adverse effects can be increased when Nafamostat is combined with Leflunomide.Investigational
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Leflunomide.Approved
Nalidixic AcidLeflunomide may increase the neuroexcitatory activities of Nalidixic Acid.Approved
NaproxenThe metabolism of Naproxen can be decreased when combined with Leflunomide.Approved, Vet Approved
NatalizumabThe risk or severity of adverse effects can be increased when Leflunomide is combined with Natalizumab.Approved, Investigational
NateglinideThe metabolism of Nateglinide can be decreased when combined with Leflunomide.Approved, Investigational
NCX 1022The risk or severity of adverse effects can be increased when Leflunomide is combined with NCX 1022.Investigational
NCX 4016The risk or severity of adverse effects can be increased when Leflunomide is combined with NCX 4016.Investigational
NeamineLeflunomide may decrease the excretion rate of Neamine which could result in a higher serum level.Experimental
NelarabineThe risk or severity of adverse effects can be increased when Nelarabine is combined with Leflunomide.Approved, Investigational
NemonoxacinLeflunomide may increase the neuroexcitatory activities of Nemonoxacin.Investigational
NeomycinLeflunomide may decrease the excretion rate of Neomycin which could result in a higher serum level.Approved, Vet Approved
NepafenacThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nepafenac.Approved
NetilmicinLeflunomide may decrease the excretion rate of Netilmicin which could result in a higher serum level.Approved
NetupitantThe metabolism of Netupitant can be decreased when combined with Leflunomide.Approved
NevirapineThe metabolism of Leflunomide can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Leflunomide can be decreased when combined with Nicardipine.Approved
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Leflunomide.Approved, Vet Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Leflunomide.Approved
Niflumic AcidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Niflumic Acid.Approved
NilotinibThe risk or severity of adverse effects can be increased when Nilotinib is combined with Leflunomide.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nimesulide.Approved, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nitroaspirin.Investigational
NorfloxacinLeflunomide may increase the neuroexcitatory activities of Norfloxacin.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Leflunomide.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Leflunomide.Approved
OfloxacinLeflunomide may increase the neuroexcitatory activities of Ofloxacin.Approved
Oleoyl estroneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Oleoyl estrone.Investigational
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Leflunomide.Approved, Investigational
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Leflunomide.Approved
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Leflunomide.Approved
OlsalazineLeflunomide may increase the nephrotoxic activities of Olsalazine.Approved
Omacetaxine mepesuccinateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Omacetaxine mepesuccinate.Approved
OmapatrilatThe risk or severity of adverse effects can be increased when Omapatrilat is combined with Leflunomide.Investigational
OmeprazoleThe metabolism of Leflunomide can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Leflunomide.Approved
OrgoteinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Orgotein.Vet Approved
OsimertinibThe serum concentration of Leflunomide can be decreased when it is combined with Osimertinib.Approved
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Leflunomide.Approved
OtamixabanLeflunomide may increase the anticoagulant activities of Otamixaban.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Leflunomide.Approved
OxaliplatinThe risk or severity of adverse effects can be increased when Oxaliplatin is combined with Leflunomide.Approved, Investigational
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Leflunomide.Approved
OxprenololLeflunomide may decrease the antihypertensive activities of Oxprenolol.Approved
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Oxyphenbutazone.Withdrawn
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Leflunomide.Approved, Vet Approved
PalbociclibThe risk or severity of adverse effects can be increased when Palbociclib is combined with Leflunomide.Approved
PamidronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Pamidronate.Approved
PanobinostatThe risk or severity of adverse effects can be increased when Panobinostat is combined with Leflunomide.Approved, Investigational
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Leflunomide.Approved
ParamethasoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Paramethasone.Approved
ParecoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Parecoxib.Approved
ParomomycinLeflunomide may decrease the excretion rate of Paromomycin which could result in a higher serum level.Approved, Investigational
PazopanibThe risk or severity of adverse effects can be increased when Pazopanib is combined with Leflunomide.Approved
PazufloxacinLeflunomide may increase the neuroexcitatory activities of Pazufloxacin.Investigational
PefloxacinLeflunomide may increase the neuroexcitatory activities of Pefloxacin.Approved
PegaspargaseThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Leflunomide.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Leflunomide can be increased when it is combined with Peginterferon alfa-2b.Approved
PemetrexedThe risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide.Approved, Investigational
PenbutololLeflunomide may decrease the antihypertensive activities of Penbutolol.Approved, Investigational
Pentosan PolysulfateLeflunomide may increase the anticoagulant activities of Pentosan Polysulfate.Approved
PentostatinThe risk or severity of adverse effects can be increased when Pentostatin is combined with Leflunomide.Approved, Investigational
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Leflunomide.Approved
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Leflunomide.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Leflunomide.Withdrawn
PhenindioneLeflunomide may increase the anticoagulant activities of Phenindione.Approved
PhenobarbitalThe metabolism of Leflunomide can be increased when combined with Phenobarbital.Approved
PhenprocoumonLeflunomide may increase the anticoagulant activities of Phenprocoumon.Approved
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Leflunomide.Approved, Vet Approved
PhenytoinThe metabolism of Leflunomide can be increased when combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Leflunomide.Approved, Investigational
PindololLeflunomide may decrease the antihypertensive activities of Pindolol.Approved
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Leflunomide.Approved, Investigational
PirarubicinThe risk or severity of adverse effects can be increased when Pirarubicin is combined with Leflunomide.Investigational
PiretanideLeflunomide may decrease the diuretic activities of Piretanide.Experimental
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Leflunomide.Investigational
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Leflunomide.Approved, Investigational
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Leflunomide.Approved
PlicamycinLeflunomide may decrease the excretion rate of Plicamycin which could result in a higher serum level.Approved, Withdrawn
PolythiazideThe therapeutic efficacy of Polythiazide can be decreased when used in combination with Leflunomide.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Leflunomide.Approved
PractololLeflunomide may decrease the antihypertensive activities of Practolol.Approved
PralatrexateThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Leflunomide.Approved
PrasteroneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Prasterone.Approved, Nutraceutical
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Leflunomide.Approved
PravastatinThe metabolism of Pravastatin can be decreased when combined with Leflunomide.Approved
PrednicarbateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Prednicarbate.Approved
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Leflunomide.Approved, Vet Approved
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Leflunomide.Approved, Vet Approved
PregnenoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Pregnenolone.Experimental
PrimidoneThe metabolism of Leflunomide can be increased when combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Leflunomide can be increased when it is combined with Probenecid.Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Leflunomide.Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Leflunomide.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Leflunomide.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Leflunomide.Approved, Vet Approved
PropacetamolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Propacetamol.Approved
PropofolThe metabolism of Propofol can be decreased when combined with Leflunomide.Approved, Investigational, Vet Approved
PropranololLeflunomide may decrease the antihypertensive activities of Propranolol.Approved, Investigational
Prostaglandin B2The therapeutic efficacy of Prostaglandin B2 can be decreased when used in combination with Leflunomide.Experimental
Prostaglandin D2The therapeutic efficacy of Prostaglandin D2 can be decreased when used in combination with Leflunomide.Experimental, Investigational
Prostaglandin G2The therapeutic efficacy of Prostaglandin G2 can be decreased when used in combination with Leflunomide.Experimental
ProstaleneThe therapeutic efficacy of Prostalene can be decreased when used in combination with Leflunomide.Vet Approved
Protein CLeflunomide may increase the anticoagulant activities of Protein C.Approved
Protein S humanLeflunomide may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeLeflunomide may increase the anticoagulant activities of Protocatechualdehyde.Approved
PrulifloxacinLeflunomide may increase the neuroexcitatory activities of Prulifloxacin.Investigational
PTC299The risk or severity of adverse effects can be increased when Leflunomide is combined with PTC299.Investigational
PuromycinLeflunomide may decrease the excretion rate of Puromycin which could result in a higher serum level.Experimental
PyrimethamineThe metabolism of Leflunomide can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Leflunomide.Approved, Illicit
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Leflunomide.Approved, Investigational
QuinethazoneThe therapeutic efficacy of Quinethazone can be decreased when used in combination with Leflunomide.Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Leflunomide.Approved
QuinineThe metabolism of Leflunomide can be decreased when combined with Quinine.Approved
Rabies vaccineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Leflunomide.Approved
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Leflunomide.Approved
RescinnamineThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Leflunomide.Approved
ResveratrolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Resveratrol.Experimental, Investigational
ReviparinLeflunomide may increase the anticoagulant activities of Reviparin.Approved
RibostamycinLeflunomide may decrease the excretion rate of Ribostamycin which could result in a higher serum level.Approved
RifampicinThe serum concentration of the active metabolites of Leflunomide can be increased when Leflunomide is used in combination with Rifampicin.Approved
RifapentineThe metabolism of Leflunomide can be increased when combined with Rifapentine.Approved
RilonaceptThe risk or severity of adverse effects can be increased when Rilonacept is combined with Leflunomide.Approved
RimexoloneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Rimexolone.Approved
RisedronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Risedronate.Approved, Investigational
RituximabThe risk or severity of adverse effects can be increased when Rituximab is combined with Leflunomide.Approved
RivaroxabanLeflunomide may increase the anticoagulant activities of Rivaroxaban.Approved
RofecoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Rofecoxib.Investigational, Withdrawn
RoflumilastRoflumilast may increase the immunosuppressive activities of Leflunomide.Approved
RolapitantThe serum concentration of Leflunomide can be increased when it is combined with Rolapitant.Approved
RopiniroleThe metabolism of Leflunomide can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Leflunomide.Approved, Investigational
RosoxacinLeflunomide may increase the neuroexcitatory activities of Rosoxacin.Approved
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Leflunomide.Approved
RuxolitinibThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Leflunomide.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Leflunomide.Approved
SalicylamideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Salicylamide.Approved
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Leflunomide.Approved, Vet Approved
SalsalateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Salsalate.Approved
SaprisartanThe risk or severity of adverse effects can be increased when Saprisartan is combined with Leflunomide.Experimental
SaralasinThe risk or severity of adverse effects can be increased when Saralasin is combined with Leflunomide.Investigational
SecobarbitalThe metabolism of Leflunomide can be increased when combined with Secobarbital.Approved, Vet Approved
SecukinumabThe risk or severity of adverse effects can be increased when Secukinumab is combined with Leflunomide.Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Leflunomide.Approved, Investigational, Vet Approved
SeocalcitolThe risk or severity of adverse effects can be increased when Seocalcitol is combined with Leflunomide.Experimental
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Leflunomide.Approved, Investigational
SertralineThe metabolism of Sertraline can be decreased when combined with Leflunomide.Approved
SildenafilThe metabolism of Leflunomide can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe risk or severity of adverse effects can be increased when Siltuximab is combined with Leflunomide.Approved
SimeprevirThe metabolism of Leflunomide can be decreased when combined with Simeprevir.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Leflunomide.Approved
SirolimusThe risk or severity of adverse effects can be increased when Sirolimus is combined with Leflunomide.Approved, Investigational
SisomicinLeflunomide may decrease the excretion rate of Sisomicin which could result in a higher serum level.Investigational
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Leflunomide.Approved, Investigational, Withdrawn
SorafenibThe risk or severity of adverse effects can be increased when Sorafenib is combined with Leflunomide.Approved, Investigational
SotalolLeflunomide may decrease the antihypertensive activities of Sotalol.Approved
SP1049CLeflunomide may decrease the excretion rate of SP1049C which could result in a higher serum level.Investigational
SparfloxacinLeflunomide may increase the neuroexcitatory activities of Sparfloxacin.Approved
SpectinomycinLeflunomide may decrease the excretion rate of Spectinomycin which could result in a higher serum level.Approved, Vet Approved
SpiraprilThe risk or severity of adverse effects can be increased when Spirapril is combined with Leflunomide.Approved
SpironolactoneLeflunomide may decrease the antihypertensive activities of Spironolactone.Approved
SRP 299The risk or severity of adverse effects can be increased when Leflunomide is combined with SRP 299.Investigational
SRT501The risk or severity of adverse effects can be increased when Leflunomide is combined with SRT501.Investigational
SteproninThe risk or severity of adverse effects can be increased when Stepronin is combined with Leflunomide.Approved
StreptomycinLeflunomide may decrease the excretion rate of Streptomycin which could result in a higher serum level.Approved, Vet Approved
StreptozocinThe risk or severity of adverse effects can be increased when Streptozocin is combined with Leflunomide.Approved
SulfadiazineThe metabolism of Leflunomide can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Leflunomide can be decreased when combined with Sulfamethoxazole.Approved
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Leflunomide.Approved
SulfasalazineLeflunomide may increase the nephrotoxic activities of Sulfasalazine.Approved
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Leflunomide.Approved
SulfisoxazoleThe metabolism of Leflunomide can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Leflunomide.Approved
SulodexideLeflunomide may increase the anticoagulant activities of Sulodexide.Approved, Investigational
SulprostoneThe therapeutic efficacy of Sulprostone can be decreased when used in combination with Leflunomide.Investigational
SunitinibThe risk or severity of adverse effects can be increased when Sunitinib is combined with Leflunomide.Approved, Investigational
SuprofenThe metabolism of Suprofen can be decreased when combined with Leflunomide.Approved, Withdrawn
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Leflunomide.Approved, Investigational
TacrolimusLeflunomide may increase the nephrotoxic activities of Tacrolimus.Approved, Investigational
TafluprostThe therapeutic efficacy of Tafluprost can be decreased when used in combination with Leflunomide.Approved
TalniflumateThe risk or severity of adverse effects can be increased when Talniflumate is combined with Leflunomide.Approved
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Leflunomide.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Leflunomide.Approved
TasosartanThe risk or severity of adverse effects can be increased when Tasosartan is combined with Leflunomide.Approved
Technetium tc 99m etidronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Technetium tc 99m etidronate.Approved
Technetium Tc-99m MedronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Technetium Tc-99m Medronate.Approved
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Leflunomide.Approved, Investigational
TemafloxacinLeflunomide may increase the neuroexcitatory activities of Temafloxacin.Withdrawn
TemazepamThe metabolism of Temazepam can be decreased when combined with Leflunomide.Approved
TemocaprilThe risk or severity of adverse effects can be increased when Temocapril is combined with Leflunomide.Experimental, Investigational
TemozolomideThe risk or severity of adverse effects can be increased when Temozolomide is combined with Leflunomide.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Temsirolimus is combined with Leflunomide.Approved
TeniposideThe risk or severity of adverse effects can be increased when Teniposide is combined with Leflunomide.Approved
TenofovirThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tenofovir.Approved, Investigational
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Leflunomide.Approved
TepoxalinThe risk or severity of adverse effects can be increased when Tepoxalin is combined with Leflunomide.Vet Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Leflunomide.Approved, Investigational, Vet Approved
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Leflunomide.Withdrawn
TeriflunomideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Teriflunomide.Approved
TestosteroneThe metabolism of Testosterone can be decreased when combined with Leflunomide.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Leflunomide is combined with TG4010.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Leflunomide.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Leflunomide can be decreased when combined with Theophylline.Approved
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Leflunomide.Approved, Vet Approved
ThiotepaThe risk or severity of adverse effects can be increased when Thiotepa is combined with Leflunomide.Approved
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiaprofenic acid.Approved
TicagrelorThe metabolism of Leflunomide can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Leflunomide can be decreased when combined with Ticlopidine.Approved
TiludronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiludronate.Approved, Vet Approved
TimololLeflunomide may decrease the antihypertensive activities of Timolol.Approved
TinoridineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tinoridine.Investigational
TioguanineThe risk or severity of adverse effects can be increased when Tioguanine is combined with Leflunomide.Approved
TixocortolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tixocortol.Approved
TobramycinLeflunomide may decrease the excretion rate of Tobramycin which could result in a higher serum level.Approved, Investigational
TocilizumabThe risk or severity of adverse effects can be increased when Tocilizumab is combined with Leflunomide.Approved
TofacitinibLeflunomide may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TolbutamideThe serum concentration of Tolbutamide can be increased when it is combined with Leflunomide.Approved
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tolfenamic Acid.Approved
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Leflunomide.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Leflunomide.Approved, Investigational
TopotecanThe risk or severity of adverse effects can be increased when Topotecan is combined with Leflunomide.Approved, Investigational
TorasemideLeflunomide may decrease the diuretic activities of Torasemide.Approved
TositumomabThe risk or severity of adverse effects can be increased when Tositumomab is combined with Leflunomide.Approved
TrabectedinThe risk or severity of adverse effects can be increased when Trabectedin is combined with Leflunomide.Approved, Investigational
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Leflunomide.Approved
TranilastThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tranilast.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Leflunomide.Approved, Investigational
Trastuzumab emtansineThe risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Leflunomide.Approved
TravoprostThe therapeutic efficacy of Travoprost can be decreased when used in combination with Leflunomide.Approved
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Leflunomide.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Leflunomide.Approved, Investigational, Nutraceutical
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Leflunomide.Approved, Vet Approved
TriamtereneLeflunomide may decrease the antihypertensive activities of Triamterene.Approved
TrichlormethiazideThe therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Leflunomide.Approved, Vet Approved
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Leflunomide.Approved
TrimethoprimThe metabolism of Leflunomide can be decreased when combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Leflunomide.Approved
Trisalicylate-cholineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Trisalicylate-choline.Approved
TrofosfamideThe risk or severity of adverse effects can be increased when Trofosfamide is combined with Leflunomide.Investigational
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Leflunomide.Withdrawn
TrovafloxacinLeflunomide may increase the neuroexcitatory activities of Trovafloxacin.Approved, Withdrawn
UnoprostoneThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Leflunomide.Approved
UstekinumabThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Leflunomide.Approved, Investigational
ValdecoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Valdecoxib.Investigational, Withdrawn
Valproic AcidThe metabolism of Leflunomide can be decreased when combined with Valproic Acid.Approved, Investigational
ValrubicinLeflunomide may decrease the excretion rate of Valrubicin which could result in a higher serum level.Approved
ValsartanThe metabolism of Leflunomide can be decreased when combined with Valsartan.Approved, Investigational
VancomycinThe serum concentration of Vancomycin can be increased when it is combined with Leflunomide.Approved
VedolizumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Leflunomide.Approved
VemurafenibThe serum concentration of Leflunomide can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Leflunomide.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Leflunomide.Approved
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Leflunomide.Investigational
VilanterolThe risk or severity of adverse effects can be increased when Vilanterol is combined with Leflunomide.Approved
VinblastineThe risk or severity of adverse effects can be increased when Vinblastine is combined with Leflunomide.Approved
VincristineThe risk or severity of adverse effects can be increased when Vincristine is combined with Leflunomide.Approved, Investigational
VindesineThe risk or severity of adverse effects can be increased when Vindesine is combined with Leflunomide.Approved
VinorelbineThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Leflunomide.Approved, Investigational
VismodegibThe metabolism of Vismodegib can be decreased when combined with Leflunomide.Approved
VoriconazoleThe metabolism of Leflunomide can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Leflunomide.Approved
WarfarinLeflunomide may increase the anticoagulant activities of Warfarin.Approved
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Leflunomide.Approved, Investigational, Withdrawn
Ym150Leflunomide may increase the anticoagulant activities of Ym150.Investigational
ZafirlukastThe metabolism of Leflunomide can be decreased when combined with Zafirlukast.Approved, Investigational
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Leflunomide.Approved
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Leflunomide.Approved
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Leflunomide.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Leflunomide.Approved, Investigational, Withdrawn
Zoledronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Zoledronic acid.Approved
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Leflunomide.Approved
ZomepiracThe risk or severity of adverse effects can be increased when Leflunomide is combined with Zomepirac.Withdrawn
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Leflunomide.Approved
ZorubicinLeflunomide may decrease the excretion rate of Zorubicin which could result in a higher serum level.Experimental
Food Interactions
  • Take without regard to meals.
References
Synthesis Reference

Ilya Avrutov, “Novel processes for making- and a new crystalline form of- leflunomide.” U.S. Patent US20010031878, issued October 18, 2001.

US20010031878
General References
  1. Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. [PubMed:10890256 ]
  2. Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743 ]
  3. Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. [PubMed:12003373 ]
  4. Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. [PubMed:11053058 ]
  5. Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033 ]
  6. Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. [PubMed:10878294 ]
  7. Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. [PubMed:10878295 ]
  8. Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414 ]
External Links
ATC CodesL04AA13
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelDownload (1.23 MB)
MSDSDownload (105 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9949
Caco-2 permeable+0.5069
P-glycoprotein substrateNon-substrate0.909
P-glycoprotein inhibitor INon-inhibitor0.7822
P-glycoprotein inhibitor IINon-inhibitor0.8889
Renal organic cation transporterNon-inhibitor0.9154
CYP450 2C9 substrateNon-substrate0.8548
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5211
CYP450 1A2 substrateInhibitor0.9189
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.5117
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5622
Ames testNon AMES toxic0.5504
CarcinogenicityNon-carcinogens0.7067
BiodegradationNot ready biodegradable0.9836
Rat acute toxicity3.0297 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9879
hERG inhibition (predictor II)Non-inhibitor0.9068
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral10 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral20 mg
Tablet, film coatedOral20 mg/1
TabletOral100 mg
TabletOral10 mg
TabletOral20 mg
TabletOral10 mg/1
TabletOral20 mg/1
Tablet, film coatedOral15 mg
Prices
Unit descriptionCostUnit
Arava 10 mg tablet24.76USD tablet
Arava 20 mg tablet24.76USD tablet
Leflunomide 10 mg tablet16.75USD tablet
Leflunomide 20 mg tablet16.75USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point165-166 °CNot Available
water solubility21 mg/L (poorly soluble)Not Available
logP2.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0844 mg/mLALOGPS
logP2.52ALOGPS
logP2.51ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)10.41ChemAxon
pKa (Strongest Basic)-0.45ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.13 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.16 m3·mol-1ChemAxon
Polarizability23.11 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-arylamides. These are organic compounds that contain a carboxamide group that is N-linked to a aryl group. They have the generic structure RC(=O)N(R')H, R = organyl group and R'= aryl group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassN-arylamides
Sub ClassNot Available
Direct ParentN-arylamides
Alternative Parents
Substituents
  • N-arylamide
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Oxazole
  • Isoxazole
  • Azole
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquinone binding
Specific Function:
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name:
DHODH
Uniprot ID:
Q02127
Molecular Weight:
42866.93 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. [PubMed:10890256 ]
  3. Prakash A, Jarvis B: Leflunomide: a review of its use in active rheumatoid arthritis. Drugs. 1999 Dec;58(6):1137-64. [PubMed:10651393 ]
  4. Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743 ]
  5. Wozel G, Pfeiffer C: [Leflunomide--a new drug for pharmacological immunomodulation]. Hautarzt. 2002 May;53(5):309-15. [PubMed:12063741 ]
  6. Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. [PubMed:12003373 ]
  7. Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. [PubMed:11053058 ]
  8. Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033 ]
  9. Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. [PubMed:10878294 ]
  10. Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. [PubMed:10878295 ]
  11. Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414 ]
  12. Fukushima R, Kanamori S, Hirashiba M, Hishikawa A, Muranaka RI, Kaneto M, Nakamura K, Kato I: Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Reprod Toxicol. 2007 Nov-Dec;24(3-4):310-6. Epub 2007 May 18. [PubMed:17604599 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and matu...
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
References
  1. O'Donnell EF, Saili KS, Koch DC, Kopparapu PR, Farrer D, Bisson WH, Mathew LK, Sengupta S, Kerkvliet NI, Tanguay RL, Kolluri SK: The anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor. PLoS One. 2010 Oct 1;5(10). pii: e13128. doi: 10.1371/journal.pone.0013128. [PubMed:20957046 ]
  2. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. [PubMed:17327465 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Signal transducer activity
Specific Function:
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migrati...
Gene Name:
PTK2B
Uniprot ID:
Q14289
Molecular Weight:
115873.62 Da
References
  1. Pytel D, Sliwinski T, Poplawski T, Ferriola D, Majsterek I: Tyrosine kinase blockers: new hope for successful cancer therapy. Anticancer Agents Med Chem. 2009 Jan;9(1):66-76. [PubMed:19149483 ]
  2. Fukushima R, Kanamori S, Hirashiba M, Hishikawa A, Muranaka RI, Kaneto M, Nakamura K, Kato I: Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Reprod Toxicol. 2007 Nov-Dec;24(3-4):310-6. Epub 2007 May 18. [PubMed:17604599 ]
  3. Steeghs N, Nortier JW, Gelderblom H: Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol. 2007 Feb;14(2):942-53. Epub 2006 Nov 14. [PubMed:17103252 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Sevilla-Mantilla C, Ortega L, Agundez JA, Fernandez-Gutierrez B, Ladero JM, Diaz-Rubio M: Leflunomide-induced acute hepatitis. Dig Liver Dis. 2004 Jan;36(1):82-4. [PubMed:14971821 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Kis E, Nagy T, Jani M, Molnar E, Janossy J, Ujhellyi O, Nemet K, Heredi-Szabo K, Krajcsi P: Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis. 2009 Jul;68(7):1201-7. doi: 10.1136/ard.2007.086264. Epub 2008 Apr 8. [PubMed:18397960 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23