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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
AravaFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
Aravatablet, film coated10 mg/1oralSanofi Aventis U.S. Llc1998-09-10Not applicableUs
AravaFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
Aravatablet, film coated20 mg/1oralSanofi Aventis U.S. Llc1998-09-10Not applicableUs
AravaFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
Aravatablet, film coated20 mg/1oralbryant ranch prepack1998-09-10Not applicableUs
AravaFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaFilm-coated tablet100 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
Aravatablet, film coated100 mg/1oralSanofi Aventis U.S. Llc1998-09-19Not applicableUs
AravaFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H1999-09-02Not applicableEu
AravaFilm-coated tablet10 mgOral useSanofi 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
Leflunomidetablet20 mgoralSanis Health Inc2010-06-15Not applicableCanada
Leflunomidetablet, film coated20 mg/1oralPrasco LLC1998-09-10Not applicableUs
Leflunomidetablet20 mgoralPro Doc Limitee2013-11-28Not applicableCanada
Leflunomidetablet, film coated20 mg/1oralWinthrop U.S.2015-09-07Not applicableUs
Leflunomidetablet10 mgoralSanis Health Inc2010-06-15Not applicableCanada
Leflunomidetablet, film coated10 mg/1oralPrasco LLC1998-09-10Not applicableUs
Leflunomidetablet, film coated10 mg/1oralWinthrop U.S.2015-09-07Not applicableUs
Leflunomidetablet10 mgoralPro Doc Limitee2013-11-28Not applicableCanada
Leflunomide WinthropFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet100 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet10 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet20 mgOral useSanofi Aventis Deutschland Gmb H2010-01-08Not applicableEu
Leflunomide WinthropFilm-coated tablet10 mgOral useSanofi 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
Leflunomidetablet, film coated10 mg/1oralPhysicians Total Care, Inc.2010-09-17Not applicableUs
Leflunomidetablet, film coated20 mg/1oralTeva Pharmaceuticals USA Inc2005-09-142015-10-31Us
Leflunomidetablet10 mg/1oralTrigen Laboratories, LLC2011-05-06Not applicableUs
Leflunomidetablet20 mg/1oralApotex Corp.2005-09-13Not applicableUs
Leflunomidetablet10 mg/1oralHeritage Pharmaceuticals Inc2009-10-29Not applicableUs
Leflunomidetablet10 mg/1oralGolden State Medical Supply, Inc.2005-09-13Not applicableUs
Leflunomidetablet20 mg/1oralTrigen Laboratories, LLC2011-05-06Not applicableUs
Leflunomidetablet20 mg/1oralDispensing Solutions, Inc.2009-10-29Not applicableUs
Leflunomidetablet20 mg/1oralHeritage Pharmaceuticals Inc2009-10-29Not applicableUs
Leflunomidetablet20 mg/1oralGolden State Medical Supply, Inc.2005-09-13Not applicableUs
Leflunomidetablet10 mg/1oralNorth Star Rx Llc2011-05-06Not applicableUs
Leflunomidetablet20 mg/1oralAvera Mc Kennan Hospital2015-03-01Not applicableUs
Leflunomidetablet, film coated20 mg/1oralPhysicians Total Care, Inc.2006-07-10Not applicableUs
Leflunomidetablet10 mg/1oralApotex Corp.2005-09-13Not applicableUs
Leflunomidetablet20 mg/1oralNorth Star Rx Llc2011-05-06Not applicableUs
Leflunomidetablet, film coated10 mg/1oralTeva Pharmaceuticals USA Inc2005-09-142015-10-31Us
Leflunomide MedacFilm-coated tablet20 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet15 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet20 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet10 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet20 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet15 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet10 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet20 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet15 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet10 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet20 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet10 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
Leflunomide MedacFilm-coated tablet15 mgOral useMedac Gesellschaft Für Klinische Spezialpräparate Mb H2010-07-27Not applicableEu
RepsoFilm-coated tablet20 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet10 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet20 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet10 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet10 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet20 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet10 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet20 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet20 mgOral useTeva B.V.2011-03-14Not applicableEu
RepsoFilm-coated tablet10 mgOral useTeva B.V.2011-03-14Not applicableEu
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Leflunomide TevaFilm-coated tablet20 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet10 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet10 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet20 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet10 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet20 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet20 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet10 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet20 mgOral useTeva Pharma B.V.2011-03-10Not applicableEu
Leflunomide TevaFilm-coated tablet10 mgOral useTeva 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 KeyInChIKey=VHOGYURTWQBHIL-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
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
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.
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.
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
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
Film-coated tabletOral use10 mg
Film-coated tabletOral use100 mg
Film-coated tabletOral use20 mg
Tablet, film coatedoral10 mg/1
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral20 mg/1
Tabletoral100 mg
Tabletoral10 mg
Tabletoral20 mg
Tabletoral10 mg/1
Tabletoral20 mg/1
Film-coated tabletOral use15 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
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)
Interactions
Drug Interactions
Drug
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Leflunomide.
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.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Leflunomide.
AbciximabLeflunomide may increase the anticoagulant activities of Abciximab.
abetimusThe risk or severity of adverse effects can be increased when abetimus is combined with Leflunomide.
AbirateroneThe serum concentration of Leflunomide can be increased when it is combined with Abiraterone.
ABR-215757The risk or severity of adverse effects can be increased when ABR-215757 is combined with Leflunomide.
AcebutololLeflunomide may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Leflunomide is combined with Aceclofenac.
AcenocoumarolLeflunomide may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Leflunomide.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Leflunomide.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Leflunomide.
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.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Leflunomide.
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Leflunomide.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Leflunomide.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Leflunomide.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Leflunomide.
Alendronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Alendronic acid.
alicaforsenThe risk or severity of adverse effects can be increased when alicaforsen is combined with Leflunomide.
AliskirenLeflunomide may decrease the antihypertensive activities of Aliskiren.
AlosetronThe metabolism of Alosetron can be decreased when combined with Leflunomide.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Leflunomide.
AlprenololLeflunomide may decrease the antihypertensive activities of Alprenolol.
AlprostadilThe therapeutic efficacy of Alprostadil can be decreased when used in combination with Leflunomide.
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.
AmikacinLeflunomide may decrease the excretion rate of Amikacin which could result in a lower serum level and potentially a reduction in efficacy.
AmilorideLeflunomide may decrease the antihypertensive activities of Amiloride.
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Leflunomide.
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Leflunomide.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Leflunomide.
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Leflunomide.
AmsacrineThe risk or severity of adverse effects can be increased when Amsacrine is combined with Leflunomide.
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide.
AncrodLeflunomide may increase the anticoagulant activities of Ancrod.
Anti-thymocyte Globulin (Rabbit)The risk or severity of adverse effects can be increased when Anti-thymocyte Globulin (Rabbit) is combined with Leflunomide.
AntipyrineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Antipyrine.
Antithrombin III humanLeflunomide may increase the anticoagulant activities of Antithrombin III human.
ApixabanLeflunomide may increase the anticoagulant activities of Apixaban.
ApremilastThe risk or severity of adverse effects can be increased when Leflunomide is combined with Apremilast.
AprepitantThe metabolism of Leflunomide can be increased when combined with Aprepitant.
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Leflunomide.
ArdeparinLeflunomide may increase the anticoagulant activities of Ardeparin.
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Leflunomide.
ArgatrobanLeflunomide may increase the anticoagulant activities of Argatroban.
ArotinololLeflunomide may decrease the antihypertensive activities of Arotinolol.
ArtemetherThe metabolism of Artemether can be decreased when combined with Leflunomide.
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Leflunomide.
AtenololLeflunomide may decrease the antihypertensive activities of Atenolol.
AzacitidineThe risk or severity of adverse effects can be increased when Azacitidine is combined with Leflunomide.
AzapropazoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Azapropazone.
AzathioprineThe risk or severity of adverse effects can be increased when Azathioprine is combined with Leflunomide.
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Leflunomide.
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Leflunomide.
AzithromycinThe metabolism of Leflunomide can be decreased when combined with Azithromycin.
BalsalazideLeflunomide may increase the nephrotoxic activities of Balsalazide.
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Leflunomide.
BasiliximabThe risk or severity of adverse effects can be increased when Basiliximab is combined with Leflunomide.
BecaplerminLeflunomide may increase the anticoagulant activities of Becaplermin.
BefunololLeflunomide may decrease the antihypertensive activities of Befunolol.
BelataceptThe risk or severity of adverse effects can be increased when Belatacept is combined with Leflunomide.
BelimumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Leflunomide.
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Leflunomide.
BendroflumethiazideThe therapeutic efficacy of Bendroflumethiazide can be decreased when used in combination with Leflunomide.
BenoxaprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Benoxaprofen.
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Leflunomide.
BetaxololLeflunomide may decrease the antihypertensive activities of Betaxolol.
BevacizumabBevacizumab may increase the cardiotoxic activities of Leflunomide.
BevantololLeflunomide may decrease the antihypertensive activities of Bevantolol.
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Leflunomide.
BimatoprostThe therapeutic efficacy of Bimatoprost can be decreased when used in combination with Leflunomide.
BisoprololLeflunomide may decrease the antihypertensive activities of Bisoprolol.
BivalirudinLeflunomide may increase the anticoagulant activities of Bivalirudin.
BleomycinThe risk or severity of adverse effects can be increased when Bleomycin is combined with Leflunomide.
BlinatumomabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.
BopindololLeflunomide may decrease the antihypertensive activities of Bopindolol.
BortezomibThe metabolism of Leflunomide can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Leflunomide.
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Leflunomide.
BriakinumabThe risk or severity of adverse effects can be increased when Briakinumab is combined with Leflunomide.
BromfenacThe risk or severity of adverse effects can be increased when Bromfenac is combined with Leflunomide.
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Leflunomide.
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Leflunomide.
BufuralolLeflunomide may decrease the antihypertensive activities of Bufuralol.
BumetanideLeflunomide may decrease the diuretic activities of Bumetanide.
BupranololLeflunomide may decrease the antihypertensive activities of Bupranolol.
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Leflunomide.
BupropionThe metabolism of Bupropion can be decreased when combined with Leflunomide.
BusulfanThe risk or severity of adverse effects can be increased when Busulfan is combined with Leflunomide.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Leflunomide.
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Leflunomide.
CaffeineThe metabolism of Leflunomide can be decreased when combined with Caffeine.
CanakinumabThe risk or severity of adverse effects can be increased when Canakinumab is combined with Leflunomide.
CandesartanThe risk or severity of adverse effects can be increased when Candesartan is combined with Leflunomide.
CandesartanThe metabolism of Candesartan can be decreased when combined with Leflunomide.
CandoxatrilThe risk or severity of adverse effects can be increased when Candoxatril is combined with Leflunomide.
CapecitabineThe risk or severity of adverse effects can be increased when Capecitabine is combined with Leflunomide.
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Leflunomide.
CarbamazepineThe metabolism of Leflunomide can be increased when combined with Carbamazepine.
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Leflunomide.
CarboplatinThe risk or severity of adverse effects can be increased when Carboplatin is combined with Leflunomide.
Carboprost TromethamineThe therapeutic efficacy of Carboprost Tromethamine can be decreased when used in combination with Leflunomide.
CarmustineThe risk or severity of adverse effects can be increased when Carmustine is combined with Leflunomide.
CarprofenThe risk or severity of adverse effects can be increased when Carprofen is combined with Leflunomide.
CarteololLeflunomide may decrease the antihypertensive activities of Carteolol.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Leflunomide.
CastanospermineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Castanospermine.
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Leflunomide.
CeliprololLeflunomide may decrease the antihypertensive activities of Celiprolol.
CeritinibThe serum concentration of Leflunomide can be increased when it is combined with Ceritinib.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Leflunomide.
CertoparinLeflunomide may increase the anticoagulant activities of Certoparin.
ChlorambucilThe risk or severity of adverse effects can be increased when Chlorambucil is combined with Leflunomide.
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Leflunomide.
ChlorothiazideThe therapeutic efficacy of Chlorothiazide can be decreased when used in combination with Leflunomide.
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Leflunomide.
ChlorthalidoneThe therapeutic efficacy of Chlorthalidone can be decreased when used in combination with Leflunomide.
CholecalciferolThe metabolism of Leflunomide can be decreased when combined with Cholecalciferol.
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.
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Leflunomide.
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Leflunomide.
CisaprideThe metabolism of Cisapride can be decreased when combined with Leflunomide.
CisplatinThe risk or severity of adverse effects can be increased when Cisplatin is combined with Leflunomide.
CitalopramThe metabolism of Leflunomide can be decreased when combined with Citalopram.
Citric AcidLeflunomide may increase the anticoagulant activities of Citric Acid.
CladribineThe risk or severity of adverse effects can be increased when Cladribine is combined with Leflunomide.
ClodronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clodronate.
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Leflunomide.
ClonixinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Clonixin.
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Leflunomide.
CloprostenolThe therapeutic efficacy of Cloprostenol can be decreased when used in combination with Leflunomide.
ClotrimazoleThe metabolism of Leflunomide can be decreased when combined with Clotrimazole.
ClozapineThe metabolism of Clozapine can be decreased when combined with Leflunomide.
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.
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.
CorticotropinThe risk or severity of adverse effects can be increased when Corticotropin is combined with Leflunomide.
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Leflunomide.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Leflunomide.
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Leflunomide.
CyclosporineLeflunomide may increase the nephrotoxic activities of Cyclosporine.
CyclosporineThe metabolism of Leflunomide can be decreased when combined with Cyclosporine.
Cyproterone acetateThe serum concentration of Leflunomide can be decreased when it is combined with Cyproterone acetate.
CytarabineThe risk or severity of adverse effects can be increased when Cytarabine is combined with Leflunomide.
D-LimoneneThe risk or severity of adverse effects can be increased when Leflunomide is combined with D-Limonene.
Dabigatran etexilateLeflunomide may increase the anticoagulant activities of Dabigatran etexilate.
DabrafenibThe serum concentration of Leflunomide can be decreased when it is combined with Dabrafenib.
DacarbazineThe risk or severity of adverse effects can be increased when Dacarbazine is combined with Leflunomide.
DaclizumabThe risk or severity of adverse effects can be increased when Daclizumab is combined with Leflunomide.
DactinomycinThe risk or severity of adverse effects can be increased when Dactinomycin is combined with Leflunomide.
DalteparinLeflunomide may increase the anticoagulant activities of Dalteparin.
DanaparoidLeflunomide may increase the anticoagulant activities of Danaparoid.
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Leflunomide.
DapsoneThe metabolism of Dapsone can be decreased when combined with Leflunomide.
DasatinibThe risk or severity of adverse effects can be increased when Dasatinib is combined with Leflunomide.
DaunorubicinThe risk or severity of adverse effects can be increased when Daunorubicin is combined with Leflunomide.
DaunorubicinLeflunomide may decrease the excretion rate of Daunorubicin which could result in a lower serum level and potentially a reduction in efficacy.
DeferasiroxThe serum concentration of Leflunomide can be increased when it is combined with Deferasirox.
DeferasiroxThe risk or severity of adverse effects can be increased when Leflunomide is combined with Deferasirox.
DelavirdineThe metabolism of Leflunomide can be decreased when combined with Delavirdine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Leflunomide.
DesirudinLeflunomide may increase the anticoagulant activities of Desirudin.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Leflunomide.
DesmopressinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Desmopressin.
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Leflunomide.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Leflunomide.
DextranLeflunomide may increase the anticoagulant activities of Dextran.
Dextran 40Leflunomide may increase the anticoagulant activities of Dextran 40.
Dextran 70Leflunomide may increase the anticoagulant activities of Dextran 70.
Dextran 75Leflunomide may increase the anticoagulant activities of Dextran 75.
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Leflunomide.
DiazepamThe metabolism of Diazepam can be decreased when combined with Leflunomide.
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Leflunomide.
DicoumarolLeflunomide may increase the anticoagulant activities of Dicoumarol.
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Leflunomide.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Leflunomide.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Leflunomide.
DigoxinDigoxin may decrease the cardiotoxic activities of Leflunomide.
DihydrostreptomycinLeflunomide may decrease the excretion rate of Dihydrostreptomycin which could result in a lower serum level and potentially a reduction in efficacy.
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Leflunomide.
Dimethyl fumarateThe risk or severity of adverse effects can be increased when Dimethyl fumarate is combined with Leflunomide.
DinoprostoneThe therapeutic efficacy of Dinoprostone can be decreased when used in combination with Leflunomide.
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Leflunomide.
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Leflunomide.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Leflunomide.
DolasetronThe metabolism of Dolasetron can be decreased when combined with Leflunomide.
DonepezilThe metabolism of Donepezil can be decreased when combined with Leflunomide.
DopamineThe metabolism of Dopamine can be decreased when combined with Leflunomide.
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Leflunomide.
DoxepinThe metabolism of Doxepin can be decreased when combined with Leflunomide.
DoxorubicinThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Leflunomide.
DoxorubicinLeflunomide may decrease the excretion rate of Doxorubicin which could result in a lower serum level and potentially a reduction in efficacy.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Leflunomide.
DrospirenoneLeflunomide may increase the hyperkalemic activities of Drospirenone.
DroxicamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Droxicam.
EculizumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Leflunomide.
Edetic AcidLeflunomide may increase the anticoagulant activities of Edetic Acid.
EdoxabanLeflunomide may increase the anticoagulant activities of Edoxaban.
EfalizumabThe risk or severity of adverse effects can be increased when Efalizumab is combined with Leflunomide.
EfavirenzThe metabolism of Leflunomide can be decreased when combined with Efavirenz.
EletriptanThe metabolism of Eletriptan can be decreased when combined with Leflunomide.
EltrombopagThe serum concentration of Leflunomide can be increased when it is combined with Eltrombopag.
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Leflunomide.
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Leflunomide.
EnoxaparinLeflunomide may increase the anticoagulant activities of Enoxaparin.
EpirizoleThe risk or severity of adverse effects can be increased when Leflunomide is combined with Epirizole.
EpirubicinThe risk or severity of adverse effects can be increased when Epirubicin is combined with Leflunomide.
EpirubicinLeflunomide may decrease the excretion rate of Epirubicin which could result in a lower serum level and potentially a reduction in efficacy.
EplerenoneLeflunomide may decrease the antihypertensive activities of Eplerenone.
EpoprostenolThe therapeutic efficacy of Epoprostenol can be decreased when used in combination with Leflunomide.
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Leflunomide.
EsmololLeflunomide may decrease the antihypertensive activities of Esmolol.
EstradiolThe metabolism of Estradiol can be decreased when combined with Leflunomide.
EstramustineThe risk or severity of adverse effects can be increased when Estramustine is combined with Leflunomide.
EstroneThe metabolism of Estrone can be decreased when combined with Leflunomide.
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Leflunomide.
Etacrynic acidLeflunomide may decrease the diuretic activities of Etacrynic acid.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Leflunomide.
Ethyl biscoumacetateLeflunomide may increase the anticoagulant activities of Ethyl biscoumacetate.
Etidronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etidronic acid.
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Leflunomide.
EtofenamateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etofenamate.
EtoposideThe risk or severity of adverse effects can be increased when Etoposide is combined with Leflunomide.
EtoricoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Etoricoxib.
EtravirineThe metabolism of Etravirine can be decreased when combined with Leflunomide.
Evening primrose oilThe risk or severity of adverse effects can be increased when Leflunomide is combined with Evening primrose oil.
EverolimusThe risk or severity of adverse effects can be increased when Everolimus is combined with Leflunomide.
exisulindThe risk or severity of adverse effects can be increased when Leflunomide is combined with exisulind.
FenbufenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Fenbufen.
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Leflunomide.
FingolimodThe risk or severity of adverse effects can be increased when Fingolimod is combined with Leflunomide.
FingolimodLeflunomide may increase the immunosuppressive activities of Fingolimod.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Leflunomide.
FloxuridineThe risk or severity of adverse effects can be increased when Floxuridine is combined with Leflunomide.
FluconazoleThe metabolism of Leflunomide can be decreased when combined with Fluconazole.
FludarabineThe risk or severity of adverse effects can be increased when Fludarabine is combined with Leflunomide.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Leflunomide.
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Leflunomide.
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Leflunomide.
FlunixinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Flunixin.
FluorouracilThe risk or severity of adverse effects can be increased when Fluorouracil is combined with Leflunomide.
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Leflunomide.
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Leflunomide.
FluvastatinThe metabolism of Leflunomide can be decreased when combined with Fluvastatin.
FluvoxamineThe metabolism of Leflunomide can be decreased when combined with Fluvoxamine.
Folic AcidThe therapeutic efficacy of Folic Acid can be decreased when used in combination with Leflunomide.
Fondaparinux sodiumLeflunomide may increase the anticoagulant activities of Fondaparinux sodium.
ForasartanThe risk or severity of adverse effects can be increased when Forasartan is combined with Leflunomide.
FormoterolThe metabolism of Formoterol can be decreased when combined with Leflunomide.
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Leflunomide.
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Leflunomide.
FramycetinLeflunomide may decrease the excretion rate of Framycetin which could result in a lower serum level and potentially a reduction in efficacy.
FurosemideLeflunomide may decrease the diuretic activities of Furosemide.
Gallium nitrateThe risk or severity of adverse effects can be increased when Gallium nitrate is combined with Leflunomide.
GavestinelThe metabolism of Gavestinel can be decreased when combined with Leflunomide.
GemcitabineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Leflunomide.
GemeprostThe therapeutic efficacy of Gemeprost can be decreased when used in combination with Leflunomide.
GemfibrozilThe metabolism of Leflunomide can be decreased when combined with Gemfibrozil.
Gemtuzumab ozogamicinThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Leflunomide.
GentamicinLeflunomide may decrease the excretion rate of Gentamicin which could result in a lower serum level and potentially a reduction in efficacy.
Glatiramer AcetateThe risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Leflunomide.
GliclazideThe metabolism of Gliclazide can be decreased when combined with Leflunomide.
GlimepirideThe risk or severity of adverse effects can be increased when Glimepiride is combined with Leflunomide.
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Leflunomide.
GlipizideThe metabolism of Glipizide can be decreased when combined with Leflunomide.
GlyburideThe metabolism of Glyburide can be decreased when combined with Leflunomide.
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Leflunomide.
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Leflunomide.
HaloperidolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Haloperidol.
HalothaneThe metabolism of Halothane can be decreased when combined with Leflunomide.
HeparinLeflunomide may increase the anticoagulant activities of Heparin.
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Leflunomide.
HirulogLeflunomide may increase the anticoagulant activities of Hirulog.
Histamine PhosphateThe metabolism of Histamine Phosphate can be decreased when combined with Leflunomide.
HMPL-004The risk or severity of adverse effects can be increased when Leflunomide is combined with HMPL-004.
HydralazineLeflunomide may decrease the antihypertensive activities of Hydralazine.
HydrochlorothiazideThe therapeutic efficacy of Hydrochlorothiazide can be decreased when used in combination with Leflunomide.
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Leflunomide.
HydroflumethiazideThe therapeutic efficacy of Hydroflumethiazide can be decreased when used in combination with Leflunomide.
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Leflunomide.
HydroxyureaThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Leflunomide.
Hygromycin BLeflunomide may decrease the excretion rate of Hygromycin B which could result in a lower serum level and potentially a reduction in efficacy.
IbandronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ibandronate.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Leflunomide.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Leflunomide.
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Leflunomide.
IbuproxamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Ibuproxam.
IcatibantThe risk or severity of adverse effects can be increased when Leflunomide is combined with Icatibant.
IdarubicinThe risk or severity of adverse effects can be increased when Idarubicin is combined with Leflunomide.
IdarubicinLeflunomide may decrease the excretion rate of Idarubicin which could result in a lower serum level and potentially a reduction in efficacy.
IdelalisibThe risk or severity of adverse effects can be increased when Idelalisib is combined with Leflunomide.
IfosfamideThe risk or severity of adverse effects can be increased when Ifosfamide is combined with Leflunomide.
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Leflunomide.
IloprostThe therapeutic efficacy of Iloprost can be decreased when used in combination with Leflunomide.
ImatinibThe risk or severity of adverse effects can be increased when Imatinib is combined with Leflunomide.
ImatinibThe metabolism of Imatinib can be decreased when combined with Leflunomide.
ImiquimodThe risk or severity of adverse effects can be increased when Imiquimod is combined with Leflunomide.
IndapamideThe therapeutic efficacy of Indapamide can be decreased when used in combination with Leflunomide.
IndenololLeflunomide may decrease the antihypertensive activities of Indenolol.
IndinavirThe metabolism of Leflunomide can be decreased when combined with Indinavir.
indisulamThe metabolism of indisulam can be decreased when combined with Leflunomide.
IndomethacinThe risk or severity of adverse effects can be increased when Indomethacin is combined with Leflunomide.
IndoprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Indoprofen.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Leflunomide.
IrbesartanThe risk or severity of adverse effects can be increased when Irbesartan is combined with Leflunomide.
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Leflunomide.
IrinotecanThe risk or severity of adverse effects can be increased when Irinotecan is combined with Leflunomide.
IsoxicamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Isoxicam.
IxazomibThe metabolism of Ixazomib can be decreased when combined with Leflunomide.
KanamycinLeflunomide may decrease the excretion rate of Kanamycin which could result in a lower serum level and potentially a reduction in efficacy.
KebuzoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Kebuzone.
KetamineThe metabolism of Ketamine can be decreased when combined with Leflunomide.
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Leflunomide.
KetoconazoleThe metabolism of Leflunomide can be decreased when combined with Ketoconazole.
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Leflunomide.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Leflunomide.
L-PhenylalanineThe risk or severity of adverse effects can be increased when L-Phenylalanine is combined with Leflunomide.
LabetalolLeflunomide may decrease the antihypertensive activities of Labetalol.
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Leflunomide.
LepirudinLeflunomide may increase the anticoagulant activities of Lepirudin.
LesinuradThe metabolism of Lesinurad can be decreased when combined with Leflunomide.
LevobunololLeflunomide may decrease the antihypertensive activities of Levobunolol.
LicofeloneThe metabolism of Licofelone can be decreased when combined with Leflunomide.
LidocaineThe metabolism of Leflunomide can be decreased when combined with Lidocaine.
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Leflunomide.
LithiumThe serum concentration of Lithium can be increased when it is combined with Leflunomide.
LomustineThe risk or severity of adverse effects can be increased when Lomustine is combined with Leflunomide.
LoratadineThe metabolism of Loratadine can be decreased when combined with Leflunomide.
LornoxicamThe risk or severity of adverse effects can be increased when Leflunomide is combined with Lornoxicam.
LosartanThe risk or severity of adverse effects can be increased when Losartan is combined with Leflunomide.
LosartanThe metabolism of Losartan can be decreased when combined with Leflunomide.
LovastatinThe metabolism of Leflunomide can be decreased when combined with Lovastatin.
LoxoprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Loxoprofen.
LubiprostoneThe therapeutic efficacy of Lubiprostone can be decreased when used in combination with Leflunomide.
LumacaftorThe serum concentration of Leflunomide can be decreased when it is combined with Lumacaftor.
LumiracoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Lumiracoxib.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Magnesium salicylate.
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Leflunomide.
MechlorethamineThe risk or severity of adverse effects can be increased when Mechlorethamine is combined with Leflunomide.
Meclofenamic acidThe risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Leflunomide.
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Leflunomide.
MelatoninThe metabolism of Melatonin can be decreased when combined with Leflunomide.
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Leflunomide.
MelphalanThe risk or severity of adverse effects can be increased when Melphalan is combined with Leflunomide.
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Leflunomide.
MepolizumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Leflunomide.
MercaptopurineThe risk or severity of adverse effects can be increased when Mercaptopurine is combined with Leflunomide.
MesalazineLeflunomide may increase the nephrotoxic activities of Mesalazine.
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Leflunomide.
MestranolThe metabolism of Mestranol can be decreased when combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Leflunomide is combined with Metamizole.
MethadoneThe metabolism of Methadone can be decreased when combined with Leflunomide.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Leflunomide.
MethotrexateThe risk or severity of adverse effects can be increased when Methotrexate is combined with Leflunomide.
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Leflunomide.
MethyclothiazideThe therapeutic efficacy of Methyclothiazide can be decreased when used in combination with Leflunomide.
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Leflunomide.
MetipranololLeflunomide may decrease the antihypertensive activities of Metipranolol.
MetolazoneThe therapeutic efficacy of Metolazone can be decreased when used in combination with Leflunomide.
MetoprololLeflunomide may decrease the antihypertensive activities of Metoprolol.
MetrizamideLeflunomide may decrease the excretion rate of Metrizamide which could result in a lower serum level and potentially a reduction in efficacy.
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Leflunomide.
MexiletineThe metabolism of Leflunomide can be decreased when combined with Mexiletine.
MifepristoneThe serum concentration of Leflunomide can be increased when it is combined with Mifepristone.
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Leflunomide.
MisoprostolThe therapeutic efficacy of Misoprostol can be decreased when used in combination with Leflunomide.
MitomycinThe risk or severity of adverse effects can be increased when Mitomycin is combined with Leflunomide.
MitoxantroneThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with Leflunomide.
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Leflunomide.
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Leflunomide.
MontelukastThe metabolism of Montelukast can be decreased when combined with Leflunomide.
MorniflumateThe risk or severity of adverse effects can be increased when Morniflumate is combined with Leflunomide.
MuromonabThe risk or severity of adverse effects can be increased when Muromonab is combined with Leflunomide.
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Leflunomide.
Mycophenolic acidThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Leflunomide.
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Leflunomide.
NadololLeflunomide may decrease the antihypertensive activities of Nadolol.
NadroparinLeflunomide may increase the anticoagulant activities of Nadroparin.
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Leflunomide.
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Natalizumab is combined with Leflunomide.
NateglinideThe metabolism of Nateglinide can be decreased when combined with Leflunomide.
NCX 4016The risk or severity of adverse effects can be increased when Leflunomide is combined with NCX 4016.
NelarabineThe risk or severity of adverse effects can be increased when Nelarabine is combined with Leflunomide.
NeomycinLeflunomide may decrease the excretion rate of Neomycin which could result in a lower serum level and potentially a reduction in efficacy.
NepafenacThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nepafenac.
NetilmicinLeflunomide may decrease the excretion rate of Netilmicin which could result in a lower serum level and potentially a reduction in efficacy.
NetupitantThe metabolism of Netupitant can be decreased when combined with Leflunomide.
NevirapineThe metabolism of Leflunomide can be decreased when combined with Nevirapine.
NicardipineThe metabolism of Leflunomide can be decreased when combined with Nicardipine.
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Leflunomide.
NicotineThe metabolism of Nicotine can be decreased when combined with Leflunomide.
Niflumic AcidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Niflumic Acid.
NilotinibThe risk or severity of adverse effects can be increased when Nilotinib is combined with Leflunomide.
NimesulideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Nimesulide.
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Leflunomide.
ObinutuzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Leflunomide.
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Leflunomide.
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Leflunomide.
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Leflunomide.
OlsalazineLeflunomide may increase the nephrotoxic activities of Olsalazine.
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Leflunomide.
Omacetaxine mepesuccinateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Omacetaxine mepesuccinate.
OmapatrilatThe risk or severity of adverse effects can be increased when Omapatrilat is combined with Leflunomide.
OmeprazoleThe metabolism of Leflunomide can be decreased when combined with Omeprazole.
OndansetronThe metabolism of Ondansetron can be decreased when combined with Leflunomide.
OrgoteinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Orgotein.
OsimertinibThe serum concentration of Leflunomide can be decreased when it is combined with Osimertinib.
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Leflunomide.
OtamixabanLeflunomide may increase the anticoagulant activities of Otamixaban.
OuabainOuabain may decrease the cardiotoxic activities of Leflunomide.
OxaliplatinThe risk or severity of adverse effects can be increased when Oxaliplatin is combined with Leflunomide.
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Leflunomide.
OxprenololLeflunomide may decrease the antihypertensive activities of Oxprenolol.
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Oxyphenbutazone.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Leflunomide.
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Leflunomide.
PalbociclibThe risk or severity of adverse effects can be increased when Palbociclib is combined with Leflunomide.
PamidronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Pamidronate.
PanobinostatThe risk or severity of adverse effects can be increased when Panobinostat is combined with Leflunomide.
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Leflunomide.
ParecoxibThe risk or severity of adverse effects can be increased when Leflunomide is combined with Parecoxib.
ParomomycinLeflunomide may decrease the excretion rate of Paromomycin which could result in a lower serum level and potentially a reduction in efficacy.
PazopanibThe risk or severity of adverse effects can be increased when Pazopanib is combined with Leflunomide.
PegaspargaseThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Leflunomide.
Peginterferon alfa-2bThe serum concentration of Leflunomide can be increased when it is combined with Peginterferon alfa-2b.
PemetrexedThe risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide.
PenbutololLeflunomide may decrease the antihypertensive activities of Penbutolol.
Pentosan PolysulfateLeflunomide may increase the anticoagulant activities of Pentosan Polysulfate.
PentostatinThe risk or severity of adverse effects can be increased when Pentostatin is combined with Leflunomide.
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Leflunomide.
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Leflunomide.
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Leflunomide.
PhenindioneLeflunomide may increase the anticoagulant activities of Phenindione.
PhenobarbitalThe metabolism of Leflunomide can be increased when combined with Phenobarbital.
PhenprocoumonLeflunomide may increase the anticoagulant activities of Phenprocoumon.
PhenylbutazoneThe risk or severity of adverse effects can be increased when Phenylbutazone is combined with Leflunomide.
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Leflunomide.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Leflunomide.
PindololLeflunomide may decrease the antihypertensive activities of Pindolol.
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Leflunomide.
PiretanideLeflunomide may decrease the diuretic activities of Piretanide.
PirfenidoneThe risk or severity of adverse effects can be increased when Leflunomide is combined with Pirfenidone.
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Leflunomide.
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Leflunomide.
PlicamycinLeflunomide may decrease the excretion rate of Plicamycin which could result in a lower serum level and potentially a reduction in efficacy.
PolythiazideThe therapeutic efficacy of Polythiazide can be decreased when used in combination with Leflunomide.
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Leflunomide.
PractololLeflunomide may decrease the antihypertensive activities of Practolol.
PralatrexateThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Leflunomide.
PralatrexateThe serum concentration of Pralatrexate can be increased when it is combined with Leflunomide.
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Leflunomide.
PravastatinThe metabolism of Pravastatin can be decreased when combined with Leflunomide.
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Leflunomide.
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Leflunomide.
PrimidoneThe metabolism of Leflunomide can be increased when combined with Primidone.
ProbenecidThe serum concentration of Leflunomide can be increased when it is combined with Probenecid.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Leflunomide.
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Leflunomide.
ProguanilThe metabolism of Proguanil can be decreased when combined with Leflunomide.
PromazineThe metabolism of Promazine can be decreased when combined with Leflunomide.
PropacetamolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Propacetamol.
PropofolThe metabolism of Propofol can be decreased when combined with Leflunomide.
PropranololLeflunomide may decrease the antihypertensive activities of Propranolol.
Prostaglandin D2The therapeutic efficacy of Prostaglandin D2 can be decreased when used in combination with Leflunomide.
Protein CLeflunomide may increase the anticoagulant activities of Protein C.
ProtocatechualdehydeLeflunomide may increase the anticoagulant activities of Protocatechualdehyde.
PTC299The risk or severity of adverse effects can be increased when Leflunomide is combined with PTC299.
PuromycinLeflunomide may decrease the excretion rate of Puromycin which could result in a lower serum level and potentially a reduction in efficacy.
PyrimethamineThe metabolism of Leflunomide can be decreased when combined with Pyrimethamine.
QuazepamThe metabolism of Quazepam can be decreased when combined with Leflunomide.
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Leflunomide.
QuinethazoneThe therapeutic efficacy of Quinethazone can be decreased when used in combination with Leflunomide.
QuinidineThe metabolism of Quinidine can be decreased when combined with Leflunomide.
QuinineThe metabolism of Leflunomide can be decreased when combined with Quinine.
Rabies vaccineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Rabies vaccine.
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Leflunomide.
RescinnamineThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Leflunomide.
ResveratrolThe risk or severity of adverse effects can be increased when Leflunomide is combined with Resveratrol.
ReviparinLeflunomide may increase the anticoagulant activities of Reviparin.
RibostamycinLeflunomide may decrease the excretion rate of Ribostamycin which could result in a lower serum level and potentially a reduction in efficacy.
RifampicinThe serum concentration of the active metabolites of Leflunomide can be increased when Leflunomide is used in combination with Rifampicin.
RifampicinThe metabolism of Rifampicin can be decreased when combined with Leflunomide.
RifapentineThe metabolism of Leflunomide can be increased when combined with Rifapentine.
RilonaceptThe risk or severity of adverse effects can be increased when Rilonacept is combined with Leflunomide.
RisedronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Risedronate.
RituximabThe risk or severity of adverse effects can be increased when Rituximab is combined with Leflunomide.
RivaroxabanLeflunomide may increase the anticoagulant activities of Rivaroxaban.
RofecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Leflunomide.
RoflumilastRoflumilast may increase the immunosuppressive activities of Leflunomide.
RolapitantThe serum concentration of Leflunomide can be increased when it is combined with Rolapitant.
RopiniroleThe metabolism of Leflunomide can be decreased when combined with Ropinirole.
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Leflunomide.
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Leflunomide.
RuxolitinibThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Leflunomide.
SalicylamideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Salicylamide.
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Leflunomide.
SalsalateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Salsalate.
SaprisartanThe risk or severity of adverse effects can be increased when Saprisartan is combined with Leflunomide.
SaralasinThe risk or severity of adverse effects can be increased when Saralasin is combined with Leflunomide.
SecobarbitalThe metabolism of Leflunomide can be increased when combined with Secobarbital.
SecukinumabThe risk or severity of adverse effects can be increased when Secukinumab is combined with Leflunomide.
SelegilineThe metabolism of Selegiline can be decreased when combined with Leflunomide.
SeocalcitolThe risk or severity of adverse effects can be increased when Seocalcitol is combined with Leflunomide.
SeratrodastThe risk or severity of adverse effects can be increased when Leflunomide is combined with Seratrodast.
SertralineThe metabolism of Sertraline can be decreased when combined with Leflunomide.
SildenafilThe metabolism of Leflunomide can be decreased when combined with Sildenafil.
SiltuximabThe risk or severity of adverse effects can be increased when Siltuximab is combined with Leflunomide.
SimeprevirThe metabolism of Leflunomide can be decreased when combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Leflunomide.
SirolimusThe risk or severity of adverse effects can be increased when Sirolimus is combined with Leflunomide.
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Leflunomide.
SorafenibThe metabolism of Leflunomide can be decreased when combined with Sorafenib.
SotalolLeflunomide may decrease the antihypertensive activities of Sotalol.
SpectinomycinLeflunomide may decrease the excretion rate of Spectinomycin which could result in a lower serum level and potentially a reduction in efficacy.
SpiraprilThe risk or severity of adverse effects can be increased when Spirapril is combined with Leflunomide.
SpironolactoneLeflunomide may decrease the antihypertensive activities of Spironolactone.
SRT501The risk or severity of adverse effects can be increased when Leflunomide is combined with SRT501.
SteproninThe risk or severity of adverse effects can be increased when Stepronin is combined with Leflunomide.
StreptomycinLeflunomide may decrease the excretion rate of Streptomycin which could result in a lower serum level and potentially a reduction in efficacy.
StreptozocinThe risk or severity of adverse effects can be increased when Streptozocin is combined with Leflunomide.
StreptozocinLeflunomide may decrease the excretion rate of Streptozocin which could result in a lower serum level and potentially a reduction in efficacy.
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Leflunomide.
SulfamethoxazoleThe metabolism of Leflunomide can be decreased when combined with Sulfamethoxazole.
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Leflunomide.
SulfasalazineLeflunomide may increase the nephrotoxic activities of Sulfasalazine.
SulfasalazineThe risk or severity of adverse effects can be increased when Sulfasalazine is combined with Leflunomide.
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Leflunomide.
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Leflunomide.
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Leflunomide.
SulodexideLeflunomide may increase the anticoagulant activities of Sulodexide.
SunitinibThe risk or severity of adverse effects can be increased when Sunitinib is combined with Leflunomide.
SuprofenThe risk or severity of adverse effects can be increased when Suprofen is combined with Leflunomide.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Leflunomide.
TacrolimusLeflunomide may increase the nephrotoxic activities of Tacrolimus.
TalniflumateThe risk or severity of adverse effects can be increased when Talniflumate is combined with Leflunomide.
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Leflunomide.
TapentadolThe metabolism of Tapentadol can be decreased when combined with Leflunomide.
TasosartanThe risk or severity of adverse effects can be increased when Tasosartan is combined with Leflunomide.
Technetium Tc-99m MedronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Technetium Tc-99m Medronate.
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Leflunomide.
TemazepamThe metabolism of Temazepam can be decreased when combined with Leflunomide.
TemocaprilThe risk or severity of adverse effects can be increased when Temocapril is combined with Leflunomide.
TemozolomideThe risk or severity of adverse effects can be increased when Temozolomide is combined with Leflunomide.
TemsirolimusThe risk or severity of adverse effects can be increased when Temsirolimus is combined with Leflunomide.
TeniposideThe risk or severity of adverse effects can be increased when Teniposide is combined with Leflunomide.
TenofovirThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tenofovir.
TenofovirThe metabolism of Leflunomide can be decreased when combined with Tenofovir.
TenoxicamThe risk or severity of adverse effects can be increased when Tenoxicam is combined with Leflunomide.
TepoxalinThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tepoxalin.
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Leflunomide.
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Leflunomide.
TeriflunomideThe serum concentration of Leflunomide can be decreased when it is combined with Teriflunomide.
TeriflunomideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Teriflunomide.
TestosteroneThe metabolism of Testosterone can be decreased when combined with Leflunomide.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Leflunomide.
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Leflunomide.
TheophyllineThe metabolism of Leflunomide can be decreased when combined with Theophylline.
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Leflunomide.
ThiotepaThe risk or severity of adverse effects can be increased when Thiotepa is combined with Leflunomide.
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiaprofenic acid.
TicagrelorThe metabolism of Leflunomide can be decreased when combined with Ticagrelor.
TiclopidineThe metabolism of Leflunomide can be decreased when combined with Ticlopidine.
TiludronateThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiludronate.
TimololLeflunomide may decrease the antihypertensive activities of Timolol.
TioguanineThe risk or severity of adverse effects can be increased when Tioguanine is combined with Leflunomide.
TobramycinLeflunomide may decrease the excretion rate of Tobramycin which could result in a lower serum level and potentially a reduction in efficacy.
TocilizumabThe risk or severity of adverse effects can be increased when Tocilizumab is combined with Leflunomide.
TofacitinibThe risk or severity of adverse effects can be increased when Tofacitinib is combined with Leflunomide.
TofacitinibLeflunomide may increase the immunosuppressive activities of Tofacitinib.
TolbutamideThe serum concentration of Tolbutamide can be increased when it is combined with Leflunomide.
TolbutamideThe metabolism of Leflunomide can be decreased when combined with Tolbutamide.
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tolfenamic Acid.
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Leflunomide.
TolterodineThe metabolism of Tolterodine can be decreased when combined with Leflunomide.
TopotecanThe risk or severity of adverse effects can be increased when Topotecan is combined with Leflunomide.
TorasemideThe metabolism of Torasemide can be decreased when combined with Leflunomide.
TositumomabThe risk or severity of adverse effects can be increased when Tositumomab is combined with Leflunomide.
TrabectedinThe risk or severity of adverse effects can be increased when Trabectedin is combined with Leflunomide.
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Leflunomide.
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Leflunomide.
TranilastThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tranilast.
TrastuzumabTrastuzumab may increase the neutropenic activities of Leflunomide.
Trastuzumab emtansineThe risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Leflunomide.
TravoprostThe therapeutic efficacy of Travoprost can be decreased when used in combination with Leflunomide.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Leflunomide.
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Leflunomide.
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Leflunomide.
TretinoinThe metabolism of Tretinoin can be decreased when combined with Leflunomide.
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Leflunomide.
TriamtereneLeflunomide may decrease the antihypertensive activities of Triamterene.
TrichlormethiazideThe therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Leflunomide.
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Leflunomide.
TrimethoprimThe metabolism of Leflunomide can be decreased when combined with Trimethoprim.
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Leflunomide.
Trisalicylate-cholineThe risk or severity of adverse effects can be increased when Leflunomide is combined with Trisalicylate-choline.
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Leflunomide.
UstekinumabThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Leflunomide.
ValdecoxibThe risk or severity of adverse effects can be increased when Valdecoxib is combined with Leflunomide.
Valproic AcidThe metabolism of Leflunomide can be decreased when combined with Valproic Acid.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Leflunomide.
ValsartanThe metabolism of Valsartan can be decreased when combined with Leflunomide.
VancomycinThe serum concentration of Vancomycin can be increased when it is combined with Leflunomide.
VedolizumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Leflunomide.
VemurafenibThe serum concentration of Leflunomide can be increased when it is combined with Vemurafenib.
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Leflunomide.
VerapamilThe metabolism of Verapamil can be decreased when combined with Leflunomide.
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Leflunomide.
VilanterolThe risk or severity of adverse effects can be increased when Vilanterol is combined with Leflunomide.
VinblastineThe risk or severity of adverse effects can be increased when Vinblastine is combined with Leflunomide.
VincristineThe risk or severity of adverse effects can be increased when Vincristine is combined with Leflunomide.
VindesineThe risk or severity of adverse effects can be increased when Vindesine is combined with Leflunomide.
VinorelbineThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Leflunomide.
VismodegibThe metabolism of Vismodegib can be decreased when combined with Leflunomide.
VoriconazoleThe metabolism of Leflunomide can be decreased when combined with Voriconazole.
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Leflunomide.
WarfarinLeflunomide may increase the anticoagulant activities of Warfarin.
XimelagatranLeflunomide may increase the anticoagulant activities of Ximelagatran.
ZafirlukastThe metabolism of Leflunomide can be decreased when combined with Zafirlukast.
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Leflunomide.
ZaltoprofenThe risk or severity of adverse effects can be increased when Leflunomide is combined with Zaltoprofen.
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Leflunomide.
ZileutonThe risk or severity of adverse effects can be increased when Zileuton is combined with Leflunomide.
Zoledronic acidThe risk or severity of adverse effects can be increased when Leflunomide is combined with Zoledronic acid.
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Leflunomide.
ZomepiracThe risk or severity of adverse effects can be increased when Leflunomide is combined with Zomepirac.
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Leflunomide.
Food Interactions
  • Take without regard to meals.

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