Leflunomide - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (3)Enzymes (2)Transporters (1)

Targets (3)Enzymes (2)Transporters (1)Biointeractions (6)

Identification

Name

Leflunomide

Accession Number

DB01097 (APRD00205)

Type

Small Molecule

Groups

Approved, Investigational

Description

Leflunomide 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

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

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 IDs

L04AA13 / SU-101 / SU101

Product Ingredients

Not Available

Product Images

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Arava	Tablet, film coated	10 mg/1	Oral	Sanofi Aventis	1998-09-10	Not applicable	US
Arava	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	100 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg/1	Oral	Sanofi Aventis	1998-09-10	Not applicable	US
Arava	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	100 mg/1	Oral	Sanofi Aventis	1998-09-19	Not applicable	US
Arava	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	1999-09-02	Not applicable	EU
Arava	Tablet, film coated	20 mg/1	Oral	bryant ranch prepack	1998-09-10	Not applicable	US
Arava 100 mg	Tablet	100 mg	Oral	Sanofi Aventis	2000-03-29	Not applicable	Canada
Arava 10mg	Tablet	10 mg	Oral	Sanofi Aventis	2000-03-29	Not applicable	Canada
Arava 20 mg	Tablet	20 mg	Oral	Sanofi Aventis	2000-03-29	Not applicable	Canada
Dom-leflunomide	Tablet	10 mg	Oral	Dominion Pharmacal	Not applicable	Not applicable	Canada
Dom-leflunomide	Tablet	20 mg	Oral	Dominion Pharmacal	Not applicable	Not applicable	Canada
Leflunomide	Tablet	20 mg	Oral	Sanis Health Inc	2010-06-15	Not applicable	Canada
Leflunomide	Tablet	10 mg	Oral	Pro Doc Limitee	2013-11-28	Not applicable	Canada
Leflunomide	Tablet, film coated	10 mg/1	Oral	Winthrop U.S.	2015-09-07	Not applicable	US
Leflunomide	Tablet, film coated	10 mg/1	Oral	Prasco, Laboratories	1998-09-10	Not applicable	US
Leflunomide	Tablet	20 mg	Oral	Pro Doc Limitee	2013-11-28	Not applicable	Canada
Leflunomide	Tablet, film coated	20 mg/1	Oral	Winthrop U.S.	2015-09-07	Not applicable	US
Leflunomide	Tablet, film coated	20 mg/1	Oral	Prasco, Laboratories	1998-09-10	Not applicable	US
Leflunomide	Tablet	10 mg	Oral	Sanis Health Inc	2010-06-15	Not applicable	Canada
Leflunomide Winthrop	Tablet, film coated	100 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	20 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Leflunomide Winthrop	Tablet, film coated	10 mg	Oral	Sanofi Aventis Deutschland Gmb H	2010-01-08	Not applicable	EU
Mylan-leflunomide	Tablet	10 mg	Oral	Mylan Pharmaceuticals	2008-11-14	2017-01-09	Canada
Mylan-leflunomide	Tablet	20 mg	Oral	Mylan Pharmaceuticals	2008-11-14	2017-01-09	Canada
Ntp-leflunomide	Tablet	10 mg	Oral	Teva	Not applicable	Not applicable	Canada
Ntp-leflunomide	Tablet	20 mg	Oral	Teva	Not applicable	Not applicable	Canada
Nu-leflunomide	Tablet	20 mg	Oral	Nu Pharm Inc	Not applicable	Not applicable	Canada
Nu-leflunomide	Tablet	10 mg	Oral	Nu Pharm Inc	Not applicable	Not applicable	Canada
PHL-leflunomide	Tablet	20 mg	Oral	Pharmel Inc	2008-10-31	Not applicable	Canada
PHL-leflunomide	Tablet	10 mg	Oral	Pharmel Inc	2008-10-31	Not applicable	Canada
PMS-leflunomide	Tablet	10 mg	Oral	Pharmascience Inc	2006-12-01	Not applicable	Canada
PMS-leflunomide	Tablet	20 mg	Oral	Pharmascience Inc	2006-12-01	Not applicable	Canada
Sandoz Leflunomide	Tablet	10 mg	Oral	Sandoz Canada Incorporated	2006-08-15	Not applicable	Canada
Sandoz Leflunomide	Tablet	20 mg	Oral	Sandoz Canada Incorporated	2006-08-15	Not applicable	Canada
Teva-leflunomide	Tablet	20 mg	Oral	Teva	2004-12-21	Not applicable	Canada
Teva-leflunomide	Tablet	10 mg	Oral	Teva	2004-12-21	Not applicable	Canada

Approved Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Apo-leflunomide	Tablet	10 mg	Oral	Apotex Corporation	2004-09-14	Not applicable	Canada
Apo-leflunomide	Tablet	20 mg	Oral	Apotex Corporation	2004-09-14	Not applicable	Canada
Leflunomide	Tablet, film coated	20 mg/1	Oral	Physicians Total Care, Inc.	2006-07-10	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Heritage	2009-10-29	Not applicable	US
Leflunomide	Tablet	10 mg/1	Oral	Trigen Laboratories, Inc.	2011-05-06	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Golden State Medical Supply	2005-09-13	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Alembic Pharmaceuticals Limited	2016-12-01	Not applicable	US
Leflunomide	Tablet, film coated	10 mg/1	Oral	Teva	2005-09-14	2015-10-31	US
Leflunomide	Tablet	10 mg/1	Oral	Apotex Corporation	2005-09-13	Not applicable	US
Leflunomide	Tablet, film coated	10 mg/1	Oral	Physicians Total Care, Inc.	2010-09-17	Not applicable	US
Leflunomide	Tablet	10 mg/1	Oral	North Star Rx Llc	2011-05-06	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Trigen Laboratories, Inc.	2011-05-06	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Dispensing Solutions, Inc.	2009-10-29	Not applicable	US
Leflunomide	Tablet	10 mg/1	Oral	Heritage	2009-10-29	Not applicable	US
Leflunomide	Tablet, film coated	20 mg/1	Oral	Teva	2005-09-14	2015-10-31	US
Leflunomide	Tablet	20 mg/1	Oral	Apotex Corporation	2005-09-13	Not applicable	US
Leflunomide	Tablet	10 mg/1	Oral	Golden State Medical Supply	2005-09-13	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	North Star Rx Llc	2011-05-06	Not applicable	US
Leflunomide	Tablet	20 mg/1	Oral	Avera Mc Kennan Hospital	2015-03-01	Not applicable	US
Leflunomide	Tablet	10 mg/1	Oral	Alembic Pharmaceuticals Limited	2016-12-01	Not applicable	US
Leflunomide Medac	Tablet, film coated	15 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	10 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	10 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	20 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	20 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	10 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	15 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	20 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	15 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	20 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	15 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	10 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Medac	Tablet, film coated	20 mg	Oral	Medac Gesellschaft Für Klinische Spezialpräparate Mb H	2010-07-27	Not applicable	EU
Leflunomide Ratiopharm	Tablet, film coated	20 mg	Oral	Ratiopharm Inc	2010-11-29	Not applicable	EU
Leflunomide Ratiopharm	Tablet, film coated	20 mg	Oral	Ratiopharm Inc	2010-11-29	Not applicable	EU
Leflunomide Ratiopharm	Tablet, film coated	10 mg	Oral	Ratiopharm Inc	2010-11-29	Not applicable	EU
Leflunomide Ratiopharm	Tablet, film coated	10 mg	Oral	Ratiopharm Inc	2010-11-29	Not applicable	EU
Repso	Tablet, film coated	10 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	20 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	10 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	10 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	20 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	10 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	20 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	20 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	10 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU
Repso	Tablet, film coated	20 mg	Oral	Teva B.V.	2011-03-14	Not applicable	EU

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Leflunomide Teva	Tablet, film coated	20 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	10 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	10 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	20 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	10 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	20 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	10 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	20 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	10 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU
Leflunomide Teva	Tablet, film coated	20 mg	Oral	Teva Pharma B.V.	2011-03-10	Not applicable	EU

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

G162GK9U4W

CAS number

75706-12-6

Weight

Average: 270.2073
Monoisotopic: 270.061612157

Chemical Formula

C₁₂H₉F₃N₂O₂

InChI Key

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

Pharmacology

Indication

For the management of the signs and symptoms of active rheumatoid arthritis (RA) to improve physical function and to slow the progression of structural damage associated with the disease. Has also been used for the prevention of acute and chronic rejection in recipients of solid organ trasnplants and is designated by the FDA as an orphan drug for this use.

Structured Indications

Pharmacodynamics

Leflunomide 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 action

Leflunomide 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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Dihydroorotate dehydrogenase (quinone), mitochondrial	Protein	yes	inhibitor	Human	Q02127	details
Aryl hydrocarbon receptor	Protein	unknown	agonist	Human	P35869	details
Protein-tyrosine kinase 2-beta	Protein	unknown	antagonist	Human	Q14289	details

Absorption

Well 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.

Substrate	Enzymes	Product
Leflunomide	Cytochrome P450 1A2	A771726	Details

Route of elimination

The 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 life

2 weeks

Clearance

Not Available

Toxicity

LD₅₀=100-250 mg/kg (acute oral toxicity)

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Cytochrome P450 1A2	---	(C;C)	C allele	ADR Directly Studied	Diarrhea, vomiting, liver toxicity, headache, insomnia, rash, alopecia, hypertension, leucopenia, asthma	Details

Interactions

Drug Interactions

Drug	Interaction	Drug group
16-Bromoepiandrosterone	The risk or severity of adverse effects can be increased when Leflunomide is combined with 16-Bromoepiandrosterone.	Investigational
19-norandrostenedione	The risk or severity of adverse effects can be increased when Leflunomide is combined with 19-norandrostenedione.	Experimental, Illicit
2-Methoxyethanol	The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Leflunomide.	Experimental
5-androstenedione	The risk or severity of adverse effects can be increased when Leflunomide is combined with 5-androstenedione.	Experimental, Illicit
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Leflunomide.	Approved
Abciximab	Leflunomide may increase the anticoagulant activities of Abciximab.	Approved
Abiraterone	The serum concentration of Leflunomide can be increased when it is combined with Abiraterone.	Approved
Acebutolol	Leflunomide may decrease the antihypertensive activities of Acebutolol.	Approved
Aceclofenac	The metabolism of Aceclofenac can be decreased when combined with Leflunomide.	Approved
Acenocoumarol	Leflunomide may increase the anticoagulant activities of Acenocoumarol.	Approved
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Leflunomide.	Approved
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Leflunomide.	Approved
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be decreased when combined with Leflunomide.	Approved, Vet Approved
Aclarubicin	Leflunomide may decrease the excretion rate of Aclarubicin which could result in a higher serum level.	Investigational
Acteoside	The risk or severity of adverse effects can be increased when Acteoside is combined with Leflunomide.	Investigational
Activated charcoal	The serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Activated charcoal resulting in a loss in efficacy.	Approved
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Leflunomide.	Approved
Adapalene	The risk or severity of adverse effects can be increased when Adapalene is combined with Leflunomide.	Approved
Adefovir Dipivoxil	The risk or severity of adverse effects can be increased when Adefovir Dipivoxil is combined with Leflunomide.	Approved, Investigational
Afelimomab	The risk or severity of adverse effects can be increased when Afelimomab is combined with Leflunomide.	Investigational
Alclometasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Alclometasone.	Approved
Aldosterone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Aldosterone.	Experimental
Alefacept	The risk or severity of adverse effects can be increased when Alefacept is combined with Leflunomide.	Approved, Withdrawn
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Leflunomide.	Approved, Investigational
Alendronic acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Alendronic acid.	Approved
Aliskiren	Leflunomide may decrease the antihypertensive activities of Aliskiren.	Approved, Investigational
Alosetron	The metabolism of Alosetron can be decreased when combined with Leflunomide.	Approved, Withdrawn
Alprazolam	The metabolism of Alprazolam can be decreased when combined with Leflunomide.	Approved, Illicit, Investigational
Alprenolol	Leflunomide may decrease the antihypertensive activities of Alprenolol.	Approved, Withdrawn
Alprostadil	The therapeutic efficacy of Alprostadil can be decreased when used in combination with Leflunomide.	Approved, Investigational
Altretamine	The risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.	Approved
Amcinonide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Amcinonide.	Approved
Amikacin	Leflunomide may decrease the excretion rate of Amikacin which could result in a higher serum level.	Approved, Vet Approved
Amiloride	Leflunomide may decrease the antihypertensive activities of Amiloride.	Approved
Aminophenazone	The metabolism of Aminophenazone can be decreased when combined with Leflunomide.	Approved, Withdrawn
Amiodarone	The metabolism of Leflunomide can be decreased when combined with Amiodarone.	Approved, Investigational
Amitriptyline	The metabolism of Amitriptyline can be decreased when combined with Leflunomide.	Approved
Amprenavir	The metabolism of Amprenavir can be decreased when combined with Leflunomide.	Approved
Amrubicin	Leflunomide may decrease the excretion rate of Amrubicin which could result in a higher serum level.	Approved, Investigational
Amsacrine	The risk or severity of adverse effects can be increased when Amsacrine is combined with Leflunomide.	Approved
Anakinra	The risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide.	Approved
Ancrod	Leflunomide may increase the anticoagulant activities of Ancrod.	Investigational
Andrographolide	The risk or severity of adverse effects can be increased when Leflunomide is combined with HMPL-004.	Investigational
Androstenedione	The risk or severity of adverse effects can be increased when Leflunomide is combined with 4-Androstenedione.	Experimental, Illicit
Anecortave	The risk or severity of adverse effects can be increased when Leflunomide is combined with Anecortave.	Investigational
Anisodamine	The risk or severity of adverse effects can be increased when Leflunomide is combined with Anisodamine.	Investigational
Antipyrine	The metabolism of Antipyrine can be decreased when combined with Leflunomide.	Approved
Antithrombin III human	Leflunomide may increase the anticoagulant activities of Antithrombin III human.	Approved
Antithymocyte immunoglobulin (rabbit)	The risk or severity of adverse effects can be increased when Anti-thymocyte Globulin (Rabbit) is combined with Leflunomide.	Approved
Apixaban	The metabolism of Apixaban can be decreased when combined with Leflunomide.	Approved
Apocynin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Acetovanillone.	Investigational
Apramycin	Leflunomide may decrease the excretion rate of Apramycin which could result in a higher serum level.	Experimental, Vet Approved
Apremilast	The risk or severity of adverse effects can be increased when Apremilast is combined with Leflunomide.	Approved, Investigational
Aprepitant	The metabolism of Leflunomide can be increased when combined with Aprepitant.	Approved, Investigational
Arachidonic Acid	The metabolism of Arachidonic Acid can be decreased when combined with Leflunomide.	Experimental
Arbekacin	Leflunomide may decrease the excretion rate of Arbekacin which could result in a higher serum level.	Approved
Ardeparin	Leflunomide may increase the anticoagulant activities of Ardeparin.	Approved, Withdrawn
Arformoterol	The metabolism of Arformoterol can be decreased when combined with Leflunomide.	Approved, Investigational
Argatroban	Leflunomide may increase the anticoagulant activities of Argatroban.	Approved, Investigational
Arotinolol	Leflunomide may decrease the antihypertensive activities of Arotinolol.	Approved
Artemether	The metabolism of Artemether can be decreased when combined with Leflunomide.	Approved
Atazanavir	The metabolism of Atazanavir can be decreased when combined with Leflunomide.	Approved, Investigational
Atenolol	Leflunomide may decrease the antihypertensive activities of Atenolol.	Approved
Azacitidine	The risk or severity of adverse effects can be increased when Azacitidine is combined with Leflunomide.	Approved, Investigational
Azapropazone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Azapropazone.	Withdrawn
Azathioprine	The risk or severity of adverse effects can be increased when Azathioprine is combined with Leflunomide.	Approved
Azelastine	The metabolism of Azelastine can be decreased when combined with Leflunomide.	Approved
Azilsartan medoxomil	The risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Leflunomide.	Approved
Azithromycin	The metabolism of Leflunomide can be decreased when combined with Azithromycin.	Approved
Balsalazide	Leflunomide may increase the nephrotoxic activities of Balsalazide.	Approved, Investigational
Basiliximab	The risk or severity of adverse effects can be increased when Basiliximab is combined with Leflunomide.	Approved, Investigational
BCG vaccine	The therapeutic efficacy of Bcg can be decreased when used in combination with Leflunomide.	Investigational
Becaplermin	Leflunomide may increase the anticoagulant activities of Becaplermin.	Approved, Investigational
Beclomethasone dipropionate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Beclomethasone dipropionate.	Approved, Investigational
Befunolol	Leflunomide may decrease the antihypertensive activities of Befunolol.	Experimental
Belatacept	The risk or severity of adverse effects can be increased when Belatacept is combined with Leflunomide.	Approved
Belimumab	The risk or severity of adverse effects can be increased when Belimumab is combined with Leflunomide.	Approved
Benazepril	The risk or severity of adverse effects can be increased when Benazepril is combined with Leflunomide.	Approved, Investigational
Bendroflumethiazide	The therapeutic efficacy of Bendroflumethiazide can be decreased when used in combination with Leflunomide.	Approved
Benoxaprofen	The risk or severity of adverse effects can be increased when Leflunomide is combined with Benoxaprofen.	Withdrawn
Benznidazole	The risk or severity of adverse effects can be increased when Benznidazole is combined with Leflunomide.	Investigational
Beraprost	The therapeutic efficacy of Beraprost can be decreased when used in combination with Leflunomide.	Investigational
Betamethasone	The risk or severity of adverse effects can be increased when Betamethasone is combined with Leflunomide.	Approved, Vet Approved
Betaxolol	Leflunomide may decrease the antihypertensive activities of Betaxolol.	Approved
Betulinic Acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Betulinic Acid.	Investigational
Bevacizumab	Bevacizumab may increase the cardiotoxic activities of Leflunomide.	Approved, Investigational
Bevantolol	Leflunomide may decrease the antihypertensive activities of Bevantolol.	Approved
Bexarotene	The metabolism of Bexarotene can be decreased when combined with Leflunomide.	Approved, Investigational
Bimatoprost	The therapeutic efficacy of Bimatoprost can be decreased when used in combination with Leflunomide.	Approved, Investigational
Bisoprolol	Leflunomide may decrease the antihypertensive activities of Bisoprolol.	Approved
Bivalirudin	Leflunomide may increase the anticoagulant activities of Bivalirudin.	Approved, Investigational
Bleomycin	The risk or severity of adverse effects can be increased when Bleomycin is combined with Leflunomide.	Approved
Blinatumomab	The risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.	Approved
Bopindolol	Leflunomide may decrease the antihypertensive activities of Bopindolol.	Approved
Bortezomib	The metabolism of Leflunomide can be decreased when combined with Bortezomib.	Approved, Investigational
Bosentan	The serum concentration of Bosentan can be increased when it is combined with Leflunomide.	Approved, Investigational
Brentuximab vedotin	The risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Leflunomide.	Approved
Briakinumab	The risk or severity of adverse effects can be increased when Briakinumab is combined with Leflunomide.	Investigational
Brodalumab	The risk or severity of adverse effects can be increased when Amg 827 is combined with Leflunomide.	Approved, Investigational
Bromfenac	The risk or severity of adverse effects can be increased when Bromfenac is combined with Leflunomide.	Approved
Brompheniramine	The metabolism of Brompheniramine can be decreased when combined with Leflunomide.	Approved
Bucillamine	The risk or severity of adverse effects can be increased when Leflunomide is combined with Bucillamine.	Investigational
Bucindolol	Leflunomide may decrease the antihypertensive activities of Bucindolol.	Investigational
Budesonide	The risk or severity of adverse effects can be increased when Budesonide is combined with Leflunomide.	Approved
Bufuralol	Leflunomide may decrease the antihypertensive activities of Bufuralol.	Experimental, Investigational
Bumetanide	Leflunomide may decrease the diuretic activities of Bumetanide.	Approved
Bupranolol	Leflunomide may decrease the antihypertensive activities of Bupranolol.	Approved
Buprenorphine	The metabolism of Buprenorphine can be decreased when combined with Leflunomide.	Approved, Illicit, Investigational, Vet Approved
Bupropion	The metabolism of Bupropion can be decreased when combined with Leflunomide.	Approved
Busulfan	The risk or severity of adverse effects can be increased when Busulfan is combined with Leflunomide.	Approved, Investigational
Cabazitaxel	The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Leflunomide.	Approved
Cabozantinib	The metabolism of Cabozantinib can be decreased when combined with Leflunomide.	Approved
Caffeine	The metabolism of Leflunomide can be decreased when combined with Caffeine.	Approved
Canakinumab	The risk or severity of adverse effects can be increased when Canakinumab is combined with Leflunomide.	Approved, Investigational
Candesartan	The metabolism of Candesartan can be decreased when combined with Leflunomide.	Approved
Candoxatril	The risk or severity of adverse effects can be increased when Candoxatril is combined with Leflunomide.	Experimental
Capecitabine	The risk or severity of adverse effects can be increased when Capecitabine is combined with Leflunomide.	Approved, Investigational
Captopril	The risk or severity of adverse effects can be increased when Captopril is combined with Leflunomide.	Approved
Carbamazepine	The metabolism of Leflunomide can be increased when combined with Carbamazepine.	Approved, Investigational
Carbinoxamine	The metabolism of Carbinoxamine can be decreased when combined with Leflunomide.	Approved
Carboplatin	The risk or severity of adverse effects can be increased when Carboplatin is combined with Leflunomide.	Approved
Carboprost Tromethamine	The therapeutic efficacy of Carboprost Tromethamine can be decreased when used in combination with Leflunomide.	Approved
Carmustine	The risk or severity of adverse effects can be increased when Carmustine is combined with Leflunomide.	Approved
Carprofen	The risk or severity of adverse effects can be increased when Carprofen is combined with Leflunomide.	Approved, Vet Approved, Withdrawn
Carteolol	Leflunomide may decrease the antihypertensive activities of Carteolol.	Approved
Carvedilol	The serum concentration of Carvedilol can be increased when it is combined with Leflunomide.	Approved, Investigational
Castanospermine	The risk or severity of adverse effects can be increased when Castanospermine is combined with Leflunomide.	Experimental
Celecoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Celecoxib.	Approved, Investigational
Celiprolol	Leflunomide may decrease the antihypertensive activities of Celiprolol.	Approved, Investigational
Ceritinib	The serum concentration of Leflunomide can be increased when it is combined with Ceritinib.	Approved
Certolizumab pegol	The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Leflunomide.	Approved
Certoparin	Leflunomide may increase the anticoagulant activities of Certoparin.	Approved
Chlorambucil	The risk or severity of adverse effects can be increased when Chlorambucil is combined with Leflunomide.	Approved
Chloroquine	The risk or severity of adverse effects can be increased when Chloroquine is combined with Leflunomide.	Approved, Vet Approved
Chlorothiazide	The therapeutic efficacy of Chlorothiazide can be decreased when used in combination with Leflunomide.	Approved, Vet Approved
Chlorpropamide	The metabolism of Chlorpropamide can be decreased when combined with Leflunomide.	Approved
Chlorthalidone	The therapeutic efficacy of Chlorthalidone can be decreased when used in combination with Leflunomide.	Approved
Cholecalciferol	The metabolism of Leflunomide can be decreased when combined with Cholecalciferol.	Approved, Nutraceutical
Cholestyramine	The serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Cholestyramine resulting in a loss in efficacy.	Approved
Choline magnesium trisalicylate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Trisalicylate-choline.	Approved
Ciclesonide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Ciclesonide.	Approved, Investigational
Cilazapril	The risk or severity of adverse effects can be increased when Cilazapril is combined with Leflunomide.	Approved
Cinnarizine	The metabolism of Cinnarizine can be decreased when combined with Leflunomide.	Approved
Cinoxacin	Leflunomide may increase the neuroexcitatory activities of Cinoxacin.	Approved, Withdrawn
Ciprofloxacin	Leflunomide may increase the neuroexcitatory activities of Ciprofloxacin.	Approved, Investigational
Cisapride	The metabolism of Cisapride can be decreased when combined with Leflunomide.	Approved, Investigational, Withdrawn
Cisplatin	The risk or severity of adverse effects can be increased when Cisplatin is combined with Leflunomide.	Approved
Citalopram	The metabolism of Leflunomide can be decreased when combined with Citalopram.	Approved
Citric Acid	Leflunomide may increase the anticoagulant activities of Citric Acid.	Nutraceutical, Vet Approved
Cladribine	The risk or severity of adverse effects can be increased when Cladribine is combined with Leflunomide.	Approved, Investigational
Clobetasol	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasol.	Investigational
Clobetasol propionate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasol propionate.	Approved
Clocortolone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clocortolone.	Approved
Clodronic Acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clodronate.	Approved, Investigational, Vet Approved
Clofarabine	The risk or severity of adverse effects can be increased when Clofarabine is combined with Leflunomide.	Approved, Investigational
Clonixin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Clonixin.	Approved
Clopidogrel	The metabolism of Clopidogrel can be decreased when combined with Leflunomide.	Approved, Nutraceutical
Clotrimazole	The metabolism of Leflunomide can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Clozapine	The metabolism of Clozapine can be decreased when combined with Leflunomide.	Approved
Colesevelam	The serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Colesevelam resulting in a loss in efficacy.	Approved
Colestipol	The serum concentration of the active metabolites of Leflunomide can be reduced when Leflunomide is used in combination with Colestipol resulting in a loss in efficacy.	Approved
Corticotropin	The risk or severity of adverse effects can be increased when Corticotropin is combined with Leflunomide.	Approved, Vet Approved
Cortisone acetate	The risk or severity of adverse effects can be increased when Cortisone acetate is combined with Leflunomide.	Approved
Curcumin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Curcumin.	Investigational
Cyclophosphamide	The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Leflunomide.	Approved, Investigational
Cyclosporine	The risk or severity of adverse effects can be increased when Cyclosporine is combined with Leflunomide.	Approved, Investigational, Vet Approved
Cyclosporine	Leflunomide may increase the nephrotoxic activities of Cyclosporine.	Approved, Investigational, Vet Approved
Cyproterone acetate	The serum concentration of Leflunomide can be decreased when it is combined with Cyproterone acetate.	Approved, Investigational
Cytarabine	The risk or severity of adverse effects can be increased when Cytarabine is combined with Leflunomide.	Approved, Investigational
Dabigatran etexilate	Leflunomide may increase the anticoagulant activities of Dabigatran etexilate.	Approved
Dabrafenib	The serum concentration of Leflunomide can be decreased when it is combined with Dabrafenib.	Approved
Dacarbazine	The risk or severity of adverse effects can be increased when Dacarbazine is combined with Leflunomide.	Approved, Investigational
Daclizumab	The risk or severity of adverse effects can be increased when Daclizumab is combined with Leflunomide.	Approved, Investigational
Dactinomycin	The risk or severity of adverse effects can be increased when Dactinomycin is combined with Leflunomide.	Approved
Dalteparin	Leflunomide may increase the anticoagulant activities of Dalteparin.	Approved
Dapagliflozin	The metabolism of Dapagliflozin can be decreased when combined with Leflunomide.	Approved
Dapsone	The metabolism of Dapsone can be decreased when combined with Leflunomide.	Approved, Investigational
Darexaban	Leflunomide may increase the anticoagulant activities of Ym150.	Investigational
Dasatinib	The risk or severity of adverse effects can be increased when Dasatinib is combined with Leflunomide.	Approved, Investigational
Daunorubicin	The risk or severity of adverse effects can be increased when Daunorubicin is combined with Leflunomide.	Approved
Deferasirox	The risk or severity of adverse effects can be increased when Leflunomide is combined with Deferasirox.	Approved, Investigational
Delavirdine	The metabolism of Leflunomide can be decreased when combined with Delavirdine.	Approved
Denosumab	The risk or severity of adverse effects can be increased when Denosumab is combined with Leflunomide.	Approved
Deoxyspergualin	The risk or severity of adverse effects can be increased when Deoxyspergualin is combined with Leflunomide.	Investigational
Desirudin	Leflunomide may increase the anticoagulant activities of Desirudin.	Approved
Deslanoside	Deslanoside may decrease the cardiotoxic activities of Leflunomide.	Approved
Desmopressin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Desmopressin.	Approved
Desoximetasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Desoximetasone.	Approved
Desoxycorticosterone Pivalate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Desoxycorticosterone Pivalate.	Experimental, Vet Approved
Dexamethasone	The risk or severity of adverse effects can be increased when Dexamethasone is combined with Leflunomide.	Approved, Investigational, Vet Approved
Dexketoprofen	The risk or severity of adverse effects can be increased when Dexketoprofen is combined with Leflunomide.	Approved
Dextran	Leflunomide may increase the anticoagulant activities of Dextran.	Approved, Vet Approved
Dextran 40	Leflunomide may increase the anticoagulant activities of Dextran 40.	Approved
Dextromethorphan	The metabolism of Dextromethorphan can be decreased when combined with Leflunomide.	Approved
Diazepam	The metabolism of Diazepam can be decreased when combined with Leflunomide.	Approved, Illicit, Vet Approved
Diclofenac	The risk or severity of adverse effects can be increased when Diclofenac is combined with Leflunomide.	Approved, Vet Approved
Diclofenac	The metabolism of Diclofenac can be decreased when combined with Leflunomide.	Approved, Vet Approved
Dicoumarol	Leflunomide may increase the anticoagulant activities of Dicoumarol.	Approved
Diflorasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Diflorasone.	Approved
Diflunisal	The risk or severity of adverse effects can be increased when Diflunisal is combined with Leflunomide.	Approved
Difluocortolone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Difluocortolone.	Approved
Difluprednate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Difluprednate.	Approved
Digitoxin	Digitoxin may decrease the cardiotoxic activities of Leflunomide.	Approved
Digoxin	The serum concentration of Digoxin can be increased when it is combined with Leflunomide.	Approved
Diltiazem	The metabolism of Diltiazem can be decreased when combined with Leflunomide.	Approved
Dimethyl fumarate	The risk or severity of adverse effects can be increased when Dimethyl fumarate is combined with Leflunomide.	Approved, Investigational
Dinoprost	The therapeutic efficacy of Dinoprost can be decreased when used in combination with Leflunomide.	Investigational
Dinoprost Tromethamine	The therapeutic efficacy of Dinoprost Tromethamine can be decreased when used in combination with Leflunomide.	Approved, Vet Approved
Dinoprostone	The therapeutic efficacy of Dinoprostone can be decreased when used in combination with Leflunomide.	Approved
Dinutuximab	The risk or severity of adverse effects can be increased when Dinutuximab is combined with Leflunomide.	Approved
Diphenhydramine	The metabolism of Diphenhydramine can be decreased when combined with Leflunomide.	Approved
Docetaxel	The risk or severity of adverse effects can be increased when Docetaxel is combined with Leflunomide.	Approved, Investigational
Dolasetron	The metabolism of Dolasetron can be decreased when combined with Leflunomide.	Approved
Donepezil	The metabolism of Donepezil can be decreased when combined with Leflunomide.	Approved
Dopamine	The metabolism of Dopamine can be decreased when combined with Leflunomide.	Approved
Dorzolamide	The metabolism of Dorzolamide can be decreased when combined with Leflunomide.	Approved
Doxepin	The metabolism of Doxepin can be decreased when combined with Leflunomide.	Approved
Doxifluridine	The risk or severity of adverse effects can be increased when Doxifluridine is combined with Leflunomide.	Investigational
Doxorubicin	The risk or severity of adverse effects can be increased when Doxorubicin is combined with Leflunomide.	Approved, Investigational
Dronabinol	The serum concentration of Dronabinol can be increased when it is combined with Leflunomide.	Approved, Illicit
Drospirenone	Leflunomide may increase the hyperkalemic activities of Drospirenone.	Approved
Droxicam	The risk or severity of adverse effects can be increased when Leflunomide is combined with Droxicam.	Approved
Duvelisib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Duvelisib.	Investigational
E-6201	The risk or severity of adverse effects can be increased when Leflunomide is combined with E6201.	Investigational
Ebselen	The risk or severity of adverse effects can be increased when Leflunomide is combined with Ebselen.	Investigational
Eculizumab	The risk or severity of adverse effects can be increased when Eculizumab is combined with Leflunomide.	Approved, Investigational
Edetic Acid	Leflunomide may increase the anticoagulant activities of Edetic Acid.	Approved, Vet Approved
Edoxaban	Leflunomide may increase the anticoagulant activities of Edoxaban.	Approved
Efalizumab	The risk or severity of adverse effects can be increased when Efalizumab is combined with Leflunomide.	Approved, Investigational
Efavirenz	The metabolism of Leflunomide can be decreased when combined with Efavirenz.	Approved, Investigational
Eletriptan	The metabolism of Eletriptan can be decreased when combined with Leflunomide.	Approved, Investigational
Eltrombopag	The serum concentration of Leflunomide can be increased when it is combined with Eltrombopag.	Approved
Enalapril	The risk or severity of adverse effects can be increased when Enalapril is combined with Leflunomide.	Approved, Vet Approved
Enalaprilat	The risk or severity of adverse effects can be increased when Enalaprilat is combined with Leflunomide.	Approved
Enoxacin	Leflunomide may increase the neuroexcitatory activities of Enoxacin.	Approved
Enoxaparin	Leflunomide may increase the anticoagulant activities of Enoxaparin.	Approved
Epirizole	The risk or severity of adverse effects can be increased when Leflunomide is combined with Epirizole.	Approved
Epirubicin	The risk or severity of adverse effects can be increased when Epirubicin is combined with Leflunomide.	Approved
Eplerenone	Leflunomide may decrease the antihypertensive activities of Eplerenone.	Approved
Epoprostenol	The metabolism of Epoprostenol can be decreased when combined with Leflunomide.	Approved
Eprosartan	The risk or severity of adverse effects can be increased when Eprosartan is combined with Leflunomide.	Approved
Equilenin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Equilenin.	Experimental
Equilin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Equilin.	Approved
Esmolol	Leflunomide may decrease the antihypertensive activities of Esmolol.	Approved
Estradiol	The metabolism of Estradiol can be decreased when combined with Leflunomide.	Approved, Investigational, Vet Approved
Estramustine	The risk or severity of adverse effects can be increased when Estramustine is combined with Leflunomide.	Approved
Estrone	The metabolism of Estrone can be decreased when combined with Leflunomide.	Approved
Estrone sulfate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Estrone sulfate.	Approved
Eszopiclone	The metabolism of Eszopiclone can be decreased when combined with Leflunomide.	Approved
Etacrynic acid	Leflunomide may decrease the diuretic activities of Etacrynic acid.	Approved
Etanercept	The risk or severity of adverse effects can be increased when Etanercept is combined with Leflunomide.	Approved, Investigational
Ethyl biscoumacetate	Leflunomide may increase the anticoagulant activities of Ethyl biscoumacetate.	Withdrawn
Etidronic acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Etidronic acid.	Approved
Etodolac	The risk or severity of adverse effects can be increased when Leflunomide is combined with Etodolac.	Approved, Investigational, Vet Approved
Etofenamate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Etofenamate.	Approved
Etoposide	The risk or severity of adverse effects can be increased when Etoposide is combined with Leflunomide.	Approved
Etoricoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Etoricoxib.	Approved, Investigational
Etravirine	The metabolism of Etravirine can be decreased when combined with Leflunomide.	Approved
Everolimus	The risk or severity of adverse effects can be increased when Everolimus is combined with Leflunomide.	Approved
Fenbufen	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fenbufen.	Approved
Fenoprofen	The risk or severity of adverse effects can be increased when Fenoprofen is combined with Leflunomide.	Approved
Fingolimod	The risk or severity of adverse effects can be increased when Fingolimod is combined with Leflunomide.	Approved, Investigational
Fleroxacin	Leflunomide may increase the neuroexcitatory activities of Fleroxacin.	Approved
Floctafenine	The risk or severity of adverse effects can be increased when Floctafenine is combined with Leflunomide.	Approved, Withdrawn
Floxuridine	The risk or severity of adverse effects can be increased when Floxuridine is combined with Leflunomide.	Approved
Fluconazole	The metabolism of Leflunomide can be decreased when combined with Fluconazole.	Approved
Fludarabine	The risk or severity of adverse effects can be increased when Fludarabine is combined with Leflunomide.	Approved
Fludrocortisone	The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Leflunomide.	Approved
Fluindione	Leflunomide may increase the anticoagulant activities of Fluindione.	Investigational
Flumequine	Leflunomide may increase the neuroexcitatory activities of Flumequine.	Withdrawn
Flumethasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Flumethasone.	Approved, Vet Approved
Flunarizine	The metabolism of Flunarizine can be decreased when combined with Leflunomide.	Approved
Flunisolide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Flunisolide.	Approved, Investigational
Flunitrazepam	The metabolism of Flunitrazepam can be decreased when combined with Leflunomide.	Approved, Illicit
Fluocinolone Acetonide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocinolone Acetonide.	Approved, Investigational, Vet Approved
Fluocinonide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocinonide.	Approved, Investigational
Fluocortolone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluocortolone.	Approved, Withdrawn
Fluorometholone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluorometholone.	Approved
Fluorouracil	The risk or severity of adverse effects can be increased when Fluorouracil is combined with Leflunomide.	Approved
Fluoxetine	The metabolism of Fluoxetine can be decreased when combined with Leflunomide.	Approved, Vet Approved
Fluprednidene	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluprednidene.	Approved, Withdrawn
Flurandrenolide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Flurandrenolide.	Approved
Flurbiprofen	The metabolism of Flurbiprofen can be decreased when combined with Leflunomide.	Approved, Investigational
Fluticasone furoate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluticasone furoate.	Approved
Fluticasone propionate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluticasone Propionate.	Approved
Fluvastatin	The metabolism of Leflunomide can be decreased when combined with Fluvastatin.	Approved
Fluvoxamine	The metabolism of Leflunomide can be decreased when combined with Fluvoxamine.	Approved, Investigational
Folic Acid	The therapeutic efficacy of Folic Acid can be decreased when used in combination with Leflunomide.	Approved, Nutraceutical, Vet Approved
Fondaparinux	Leflunomide may increase the anticoagulant activities of Fondaparinux.	Investigational
Fondaparinux sodium	Leflunomide may increase the anticoagulant activities of Fondaparinux sodium.	Approved, Investigational
Forasartan	The risk or severity of adverse effects can be increased when Forasartan is combined with Leflunomide.	Experimental
Formestane	The risk or severity of adverse effects can be increased when Leflunomide is combined with Formestane.	Approved, Investigational, Withdrawn
Formoterol	The metabolism of Formoterol can be decreased when combined with Leflunomide.	Approved, Investigational
Fosinopril	The risk or severity of adverse effects can be increased when Fosinopril is combined with Leflunomide.	Approved
Fosphenytoin	The metabolism of Leflunomide can be increased when combined with Fosphenytoin.	Approved
Framycetin	Leflunomide may decrease the excretion rate of Framycetin which could result in a higher serum level.	Approved
Furosemide	Leflunomide may decrease the diuretic activities of Furosemide.	Approved, Vet Approved
G17DT	The risk or severity of adverse effects can be increased when Leflunomide is combined with G17DT.	Investigational
Gabexate	Leflunomide may increase the anticoagulant activities of Gabexate.	Investigational
Gallium nitrate	The risk or severity of adverse effects can be increased when Gallium nitrate is combined with Leflunomide.	Approved, Investigational
Gatifloxacin	Leflunomide may increase the neuroexcitatory activities of Gatifloxacin.	Approved, Investigational
Gavestinel	The metabolism of Gavestinel can be decreased when combined with Leflunomide.	Investigational
Gemcitabine	The risk or severity of adverse effects can be increased when Gemcitabine is combined with Leflunomide.	Approved
Gemeprost	The therapeutic efficacy of Gemeprost can be decreased when used in combination with Leflunomide.	Approved, Withdrawn
Gemfibrozil	The metabolism of Leflunomide can be decreased when combined with Gemfibrozil.	Approved
Gemifloxacin	Leflunomide may increase the neuroexcitatory activities of Gemifloxacin.	Approved, Investigational
Gemtuzumab ozogamicin	The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Leflunomide.	Approved, Investigational, Withdrawn
Geneticin	Leflunomide may decrease the excretion rate of Geneticin which could result in a higher serum level.	Experimental
Gentamicin	Leflunomide may decrease the excretion rate of Gentamicin which could result in a higher serum level.	Approved, Vet Approved
GENTAMICIN C1A	Leflunomide may decrease the excretion rate of GENTAMICIN C1A which could result in a higher serum level.	Experimental
Glatiramer Acetate	The risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Leflunomide.	Approved, Investigational
Gliclazide	The metabolism of Gliclazide can be decreased when combined with Leflunomide.	Approved
Glimepiride	The risk or severity of adverse effects can be increased when Glimepiride is combined with Leflunomide.	Approved
Glipizide	The metabolism of Glipizide can be decreased when combined with Leflunomide.	Approved
Glyburide	The metabolism of Glyburide can be decreased when combined with Leflunomide.	Approved
Golimumab	The risk or severity of adverse effects can be increased when Golimumab is combined with Leflunomide.	Approved
Grepafloxacin	Leflunomide may increase the neuroexcitatory activities of Grepafloxacin.	Withdrawn
Guanfacine	The metabolism of Guanfacine can be decreased when combined with Leflunomide.	Approved, Investigational
Gusperimus	The risk or severity of adverse effects can be increased when Gusperimus is combined with Leflunomide.	Investigational
Haloperidol	The risk or severity of adverse effects can be increased when Leflunomide is combined with Haloperidol.	Approved
Halothane	The metabolism of Halothane can be decreased when combined with Leflunomide.	Approved, Vet Approved
HE3286	The risk or severity of adverse effects can be increased when Leflunomide is combined with HE3286.	Investigational
Heparin	Leflunomide may increase the anticoagulant activities of Heparin.	Approved, Investigational
Hexobarbital	The metabolism of Hexobarbital can be decreased when combined with Leflunomide.	Approved
Higenamine	The risk or severity of adverse effects can be increased when Leflunomide is combined with Higenamine.	Investigational
Histamine	The metabolism of Histamine Phosphate can be decreased when combined with Leflunomide.	Approved, Investigational
Human C1-esterase inhibitor	The risk or severity of adverse effects can be increased when C1 Esterase Inhibitor (Human) is combined with Leflunomide.	Approved
Hydralazine	Leflunomide may decrease the antihypertensive activities of Hydralazine.	Approved
Hydrochlorothiazide	The therapeutic efficacy of Hydrochlorothiazide can be decreased when used in combination with Leflunomide.	Approved, Vet Approved
Hydrocortisone	The risk or severity of adverse effects can be increased when Hydrocortisone is combined with Leflunomide.	Approved, Vet Approved
Hydroflumethiazide	The therapeutic efficacy of Hydroflumethiazide can be decreased when used in combination with Leflunomide.	Approved
Hydromorphone	The metabolism of Hydromorphone can be decreased when combined with Leflunomide.	Approved, Illicit
Hydroxyurea	The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Leflunomide.	Approved
Ibandronate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Ibandronate.	Approved, Investigational
Ibritumomab tiuxetan	The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Leflunomide.	Approved
Ibrutinib	The risk or severity of adverse effects can be increased when Ibrutinib is combined with Leflunomide.	Approved
Ibuprofen	The metabolism of Ibuprofen can be decreased when combined with Leflunomide.	Approved
Ibuproxam	The risk or severity of adverse effects can be increased when Leflunomide is combined with Ibuproxam.	Withdrawn
Icatibant	The risk or severity of adverse effects can be increased when Icatibant is combined with Leflunomide.	Approved
Idarubicin	The risk or severity of adverse effects can be increased when Idarubicin is combined with Leflunomide.	Approved
Idelalisib	The risk or severity of adverse effects can be increased when Idelalisib is combined with Leflunomide.	Approved
Ifosfamide	The risk or severity of adverse effects can be increased when Ifosfamide is combined with Leflunomide.	Approved
Iloprost	The therapeutic efficacy of Iloprost can be decreased when used in combination with Leflunomide.	Approved, Investigational
Imatinib	The risk or severity of adverse effects can be increased when Imatinib is combined with Leflunomide.	Approved
Imidapril	The risk or severity of adverse effects can be increased when Imidapril is combined with Leflunomide.	Investigational
Imiquimod	The risk or severity of adverse effects can be increased when Imiquimod is combined with Leflunomide.	Approved, Investigational
Indapamide	The therapeutic efficacy of Indapamide can be decreased when used in combination with Leflunomide.	Approved
Indenolol	Leflunomide may decrease the antihypertensive activities of Indenolol.	Withdrawn
Indinavir	The metabolism of Leflunomide can be decreased when combined with Indinavir.	Approved
Indomethacin	The metabolism of Indomethacin can be decreased when combined with Leflunomide.	Approved, Investigational
Indoprofen	The risk or severity of adverse effects can be increased when Leflunomide is combined with Indoprofen.	Withdrawn
Infliximab	The risk or severity of adverse effects can be increased when Infliximab is combined with Leflunomide.	Approved
INGN 201	The risk or severity of adverse effects can be increased when Leflunomide is combined with INGN 201.	Investigational
INGN 225	The risk or severity of adverse effects can be increased when Leflunomide is combined with INGN 225.	Investigational
Irbesartan	The metabolism of Leflunomide can be decreased when combined with Irbesartan.	Approved, Investigational
Irinotecan	The risk or severity of adverse effects can be increased when Irinotecan is combined with Leflunomide.	Approved, Investigational
Isoxicam	The risk or severity of adverse effects can be increased when Leflunomide is combined with Isoxicam.	Withdrawn
Ixazomib	The metabolism of Ixazomib can be decreased when combined with Leflunomide.	Approved
Kanamycin	Leflunomide may decrease the excretion rate of Kanamycin which could result in a higher serum level.	Approved, Vet Approved
Kebuzone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Kebuzone.	Experimental
Ketamine	The metabolism of Ketamine can be decreased when combined with Leflunomide.	Approved, Vet Approved
Ketobemidone	The metabolism of Ketobemidone can be decreased when combined with Leflunomide.	Approved
Ketoconazole	The metabolism of Leflunomide can be decreased when combined with Ketoconazole.	Approved, Investigational
Ketoprofen	The metabolism of Ketoprofen can be decreased when combined with Leflunomide.	Approved, Vet Approved
Ketorolac	The risk or severity of adverse effects can be increased when Ketorolac is combined with Leflunomide.	Approved
L-Phenylalanine	The risk or severity of adverse effects can be increased when L-Phenylalanine is combined with Leflunomide.	Approved, Nutraceutical
Labetalol	Leflunomide may decrease the antihypertensive activities of Labetalol.	Approved
Landiolol	Leflunomide may decrease the antihypertensive activities of Aop200704.	Investigational
Lansoprazole	The metabolism of Lansoprazole can be decreased when combined with Leflunomide.	Approved, Investigational
Latanoprost	The therapeutic efficacy of Latanoprost can be decreased when used in combination with Leflunomide.	Approved, Investigational
Lenalidomide	The risk or severity of adverse effects can be increased when Lenalidomide is combined with Leflunomide.	Approved
Lepirudin	Leflunomide may increase the anticoagulant activities of Lepirudin.	Approved
Lesinurad	The metabolism of Lesinurad can be decreased when combined with Leflunomide.	Approved
Levobunolol	Leflunomide may decrease the antihypertensive activities of Levobunolol.	Approved
Levofloxacin	Leflunomide may increase the neuroexcitatory activities of Levofloxacin.	Approved, Investigational
Licofelone	The metabolism of Licofelone can be decreased when combined with Leflunomide.	Investigational
Lidocaine	The metabolism of Leflunomide can be decreased when combined with Lidocaine.	Approved, Vet Approved
Limaprost	The therapeutic efficacy of Limaprost can be decreased when used in combination with Leflunomide.	Approved
Lisinopril	The risk or severity of adverse effects can be increased when Lisinopril is combined with Leflunomide.	Approved, Investigational
Lisofylline	The risk or severity of adverse effects can be increased when Lisofylline is combined with Leflunomide.	Investigational
Lithium	The serum concentration of Lithium can be increased when it is combined with Leflunomide.	Approved
Lomefloxacin	Leflunomide may increase the neuroexcitatory activities of Lomefloxacin.	Approved
Lomustine	The risk or severity of adverse effects can be increased when Lomustine is combined with Leflunomide.	Approved
Loratadine	The metabolism of Loratadine can be decreased when combined with Leflunomide.	Approved
Lornoxicam	The metabolism of Lornoxicam can be decreased when combined with Leflunomide.	Approved
Losartan	The metabolism of Leflunomide can be decreased when combined with Losartan.	Approved
Lovastatin	The metabolism of Leflunomide can be decreased when combined with Lovastatin.	Approved, Investigational
Loxoprofen	The risk or severity of adverse effects can be increased when Leflunomide is combined with Loxoprofen.	Approved
Lubiprostone	The therapeutic efficacy of Lubiprostone can be decreased when used in combination with Leflunomide.	Approved, Investigational
Lumacaftor	The serum concentration of Leflunomide can be decreased when it is combined with Lumacaftor.	Approved
Lumiracoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Lumiracoxib.	Approved, Investigational
Magnesium salicylate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Magnesium salicylate.	Approved
Masoprocol	The risk or severity of adverse effects can be increased when Masoprocol is combined with Leflunomide.	Approved
ME-609	The risk or severity of adverse effects can be increased when Leflunomide is combined with ME-609.	Investigational
Mechlorethamine	The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Leflunomide.	Approved
Meclofenamic acid	The risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Leflunomide.	Approved, Vet Approved
Medrysone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Medrysone.	Approved
Mefenamic acid	The metabolism of Mefenamic acid can be decreased when combined with Leflunomide.	Approved
Melatonin	The metabolism of Melatonin can be decreased when combined with Leflunomide.	Approved, Nutraceutical, Vet Approved
Meloxicam	The metabolism of Meloxicam can be decreased when combined with Leflunomide.	Approved, Vet Approved
Melphalan	The risk or severity of adverse effects can be increased when Melphalan is combined with Leflunomide.	Approved
Mephenytoin	The metabolism of Mephenytoin can be decreased when combined with Leflunomide.	Investigational, Withdrawn
Mepolizumab	The risk or severity of adverse effects can be increased when Mepolizumab is combined with Leflunomide.	Approved, Investigational
Mercaptopurine	The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Leflunomide.	Approved
Mesalazine	Leflunomide may increase the nephrotoxic activities of Mesalazine.	Approved
Mestranol	The metabolism of Mestranol can be decreased when combined with Leflunomide.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Leflunomide is combined with Metamizole.	Withdrawn
Methadone	The metabolism of Methadone can be decreased when combined with Leflunomide.	Approved
Methotrexate	The risk or severity of adverse effects can be increased when Methotrexate is combined with Leflunomide.	Approved
Methoxyflurane	The metabolism of Methoxyflurane can be decreased when combined with Leflunomide.	Approved, Vet Approved
Methyclothiazide	The therapeutic efficacy of Methyclothiazide can be decreased when used in combination with Leflunomide.	Approved
Methylprednisolone	The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Leflunomide.	Approved, Vet Approved
Metipranolol	Leflunomide may decrease the antihypertensive activities of Metipranolol.	Approved
Metolazone	The therapeutic efficacy of Metolazone can be decreased when used in combination with Leflunomide.	Approved
Metoprolol	Leflunomide may decrease the antihypertensive activities of Metoprolol.	Approved, Investigational
Metrizamide	Leflunomide may decrease the excretion rate of Metrizamide which could result in a higher serum level.	Approved
Metronidazole	The metabolism of Metronidazole can be decreased when combined with Leflunomide.	Approved
Mexiletine	The metabolism of Leflunomide can be decreased when combined with Mexiletine.	Approved
Mifepristone	The serum concentration of Leflunomide can be increased when it is combined with Mifepristone.	Approved, Investigational
Mirtazapine	The metabolism of Mirtazapine can be decreased when combined with Leflunomide.	Approved
Misoprostol	The therapeutic efficacy of Misoprostol can be decreased when used in combination with Leflunomide.	Approved
Mitomycin	The risk or severity of adverse effects can be increased when Mitomycin is combined with Leflunomide.	Approved
Mitoxantrone	The risk or severity of adverse effects can be increased when Mitoxantrone is combined with Leflunomide.	Approved, Investigational
Mizoribine	The risk or severity of adverse effects can be increased when Mizoribine is combined with Leflunomide.	Investigational
Moclobemide	The metabolism of Moclobemide can be decreased when combined with Leflunomide.	Approved
Moexipril	The risk or severity of adverse effects can be increased when Moexipril is combined with Leflunomide.	Approved
Mometasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Mometasone.	Approved, Vet Approved
Montelukast	The metabolism of Montelukast can be decreased when combined with Leflunomide.	Approved
Morniflumate	The risk or severity of adverse effects can be increased when Morniflumate is combined with Leflunomide.	Approved
Moxifloxacin	Leflunomide may increase the neuroexcitatory activities of Moxifloxacin.	Approved, Investigational
Muromonab	The risk or severity of adverse effects can be increased when Muromonab is combined with Leflunomide.	Approved, Investigational
Mycophenolate mofetil	The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Leflunomide.	Approved, Investigational
Mycophenolic acid	The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Leflunomide.	Approved
Nabumetone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Nabumetone.	Approved
Nadolol	Leflunomide may decrease the antihypertensive activities of Nadolol.	Approved
Nadroparin	Leflunomide may increase the anticoagulant activities of Nadroparin.	Approved
Nafamostat	The risk or severity of adverse effects can be increased when Nafamostat is combined with Leflunomide.	Approved, Investigational
Naftifine	The risk or severity of adverse effects can be increased when Naftifine is combined with Leflunomide.	Approved
Nalidixic Acid	Leflunomide may increase the neuroexcitatory activities of Nalidixic Acid.	Approved
Naproxen	The metabolism of Naproxen can be decreased when combined with Leflunomide.	Approved, Vet Approved
Natalizumab	The risk or severity of adverse effects can be increased when Leflunomide is combined with Natalizumab.	Approved, Investigational
Nateglinide	The metabolism of Nateglinide can be decreased when combined with Leflunomide.	Approved, Investigational
NCX 1022	The risk or severity of adverse effects can be increased when Leflunomide is combined with NCX 1022.	Investigational
NCX 4016	The risk or severity of adverse effects can be increased when Leflunomide is combined with NCX 4016.	Investigational
Neamine	Leflunomide may decrease the excretion rate of Neamine which could result in a higher serum level.	Experimental
Nelarabine	The risk or severity of adverse effects can be increased when Nelarabine is combined with Leflunomide.	Approved, Investigational
Neomycin	Leflunomide may decrease the excretion rate of Neomycin which could result in a higher serum level.	Approved, Vet Approved
Nepafenac	The risk or severity of adverse effects can be increased when Leflunomide is combined with Nepafenac.	Approved
Netilmicin	Leflunomide may decrease the excretion rate of Netilmicin which could result in a higher serum level.	Approved
Netupitant	The metabolism of Netupitant can be decreased when combined with Leflunomide.	Approved
Nevirapine	The metabolism of Leflunomide can be decreased when combined with Nevirapine.	Approved
Nicardipine	The metabolism of Leflunomide can be decreased when combined with Nicardipine.	Approved
Niclosamide	The metabolism of Niclosamide can be decreased when combined with Leflunomide.	Approved, Vet Approved
Nicotine	The metabolism of Nicotine can be decreased when combined with Leflunomide.	Approved
Niflumic Acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Niflumic Acid.	Approved
Nilotinib	The risk or severity of adverse effects can be increased when Nilotinib is combined with Leflunomide.	Approved, Investigational
Nimesulide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Nimesulide.	Approved, Withdrawn
Nitroaspirin	The risk or severity of adverse effects can be increased when Leflunomide is combined with Nitroaspirin.	Investigational
Norfloxacin	Leflunomide may increase the neuroexcitatory activities of Norfloxacin.	Approved
Nortriptyline	The metabolism of Nortriptyline can be decreased when combined with Leflunomide.	Approved
Obinutuzumab	The risk or severity of adverse effects can be increased when Obinutuzumab is combined with Leflunomide.	Approved
Ofloxacin	Leflunomide may increase the neuroexcitatory activities of Ofloxacin.	Approved
Oleandrin	Anvirzel may decrease the cardiotoxic activities of Leflunomide.	Experimental
Oleoyl-estrone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Oleoyl estrone.	Investigational
Olmesartan	The risk or severity of adverse effects can be increased when Olmesartan is combined with Leflunomide.	Approved, Investigational
Olodaterol	The metabolism of Olodaterol can be decreased when combined with Leflunomide.	Approved
Olopatadine	The risk or severity of adverse effects can be increased when Olopatadine is combined with Leflunomide.	Approved
Olsalazine	Leflunomide may increase the nephrotoxic activities of Olsalazine.	Approved
Omacetaxine mepesuccinate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Omacetaxine mepesuccinate.	Approved
Omapatrilat	The risk or severity of adverse effects can be increased when Omapatrilat is combined with Leflunomide.	Investigational
Omeprazole	The metabolism of Leflunomide can be decreased when combined with Omeprazole.	Approved, Investigational, Vet Approved
Ondansetron	The metabolism of Ondansetron can be decreased when combined with Leflunomide.	Approved
Osimertinib	The serum concentration of Leflunomide can be decreased when it is combined with Osimertinib.	Approved
Ospemifene	The metabolism of Ospemifene can be decreased when combined with Leflunomide.	Approved
Ouabain	Ouabain may decrease the cardiotoxic activities of Leflunomide.	Approved
Oxaliplatin	The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Leflunomide.	Approved, Investigational
Oxaprozin	The metabolism of Oxaprozin can be decreased when combined with Leflunomide.	Approved
Oxprenolol	Leflunomide may decrease the antihypertensive activities of Oxprenolol.	Approved
Oxyphenbutazone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Oxyphenbutazone.	Withdrawn
Paclitaxel	The risk or severity of adverse effects can be increased when Paclitaxel is combined with Leflunomide.	Approved, Vet Approved
Palbociclib	The risk or severity of adverse effects can be increased when Palbociclib is combined with Leflunomide.	Approved
Pamidronate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Pamidronate.	Approved
Panobinostat	The risk or severity of adverse effects can be increased when Panobinostat is combined with Leflunomide.	Approved, Investigational
Paramethadione	The metabolism of Paramethadione can be decreased when combined with Leflunomide.	Approved
Paramethasone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Paramethasone.	Approved
Parecoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Parecoxib.	Approved
Paromomycin	Leflunomide may decrease the excretion rate of Paromomycin which could result in a higher serum level.	Approved, Investigational
Pazopanib	The risk or severity of adverse effects can be increased when Pazopanib is combined with Leflunomide.	Approved
Pazufloxacin	Leflunomide may increase the neuroexcitatory activities of Pazufloxacin.	Investigational
Pefloxacin	Leflunomide may increase the neuroexcitatory activities of Pefloxacin.	Approved
Pegaspargase	The risk or severity of adverse effects can be increased when Pegaspargase is combined with Leflunomide.	Approved, Investigational
Peginterferon alfa-2b	The serum concentration of Leflunomide can be increased when it is combined with Peginterferon alfa-2b.	Approved
Pemetrexed	The risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide.	Approved, Investigational
Penbutolol	Leflunomide may decrease the antihypertensive activities of Penbutolol.	Approved, Investigational
Pentosan Polysulfate	Leflunomide may increase the anticoagulant activities of Pentosan Polysulfate.	Approved
Pentostatin	The risk or severity of adverse effects can be increased when Pentostatin is combined with Leflunomide.	Approved, Investigational
Perindopril	The risk or severity of adverse effects can be increased when Perindopril is combined with Leflunomide.	Approved
Perphenazine	The metabolism of Perphenazine can be decreased when combined with Leflunomide.	Approved
Phenacetin	The metabolism of Phenacetin can be decreased when combined with Leflunomide.	Withdrawn
Phenindione	Leflunomide may increase the anticoagulant activities of Phenindione.	Approved
Phenobarbital	The metabolism of Leflunomide can be increased when combined with Phenobarbital.	Approved
Phenprocoumon	Leflunomide may increase the anticoagulant activities of Phenprocoumon.	Approved
Phenylbutazone	The metabolism of Phenylbutazone can be decreased when combined with Leflunomide.	Approved, Vet Approved
Phenytoin	The metabolism of Leflunomide can be increased when combined with Phenytoin.	Approved, Vet Approved
Pimecrolimus	The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Leflunomide.	Approved, Investigational
Pindolol	Leflunomide may decrease the antihypertensive activities of Pindolol.	Approved
Pioglitazone	The metabolism of Pioglitazone can be decreased when combined with Leflunomide.	Approved, Investigational
Pirarubicin	The risk or severity of adverse effects can be increased when Pirarubicin is combined with Leflunomide.	Investigational
Piretanide	Leflunomide may decrease the diuretic activities of Piretanide.	Experimental
Pirfenidone	The risk or severity of adverse effects can be increased when Pirfenidone is combined with Leflunomide.	Investigational
Piroxicam	The metabolism of Piroxicam can be decreased when combined with Leflunomide.	Approved, Investigational
Pitavastatin	The metabolism of Pitavastatin can be decreased when combined with Leflunomide.	Approved
Plicamycin	Leflunomide may decrease the excretion rate of Plicamycin which could result in a higher serum level.	Approved, Withdrawn
Polythiazide	The therapeutic efficacy of Polythiazide can be decreased when used in combination with Leflunomide.	Approved
Pomalidomide	The risk or severity of adverse effects can be increased when Pomalidomide is combined with Leflunomide.	Approved
Practolol	Leflunomide may decrease the antihypertensive activities of Practolol.	Approved
Pralatrexate	The risk or severity of adverse effects can be increased when Pralatrexate is combined with Leflunomide.	Approved
Prasterone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Prasterone.	Approved, Nutraceutical
Prasterone sulfate	The risk or severity of adverse effects can be increased when Leflunomide is combined with dehydroepiandrosterone sulfate.	Investigational
Prasugrel	The metabolism of Prasugrel can be decreased when combined with Leflunomide.	Approved
Pravastatin	The metabolism of Pravastatin can be decreased when combined with Leflunomide.	Approved
Prednicarbate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Prednicarbate.	Approved
Prednisolone	The risk or severity of adverse effects can be increased when Prednisolone is combined with Leflunomide.	Approved, Vet Approved
Prednisone	The risk or severity of adverse effects can be increased when Prednisone is combined with Leflunomide.	Approved, Vet Approved
Pregnenolone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Pregnenolone.	Experimental
Primidone	The metabolism of Leflunomide can be increased when combined with Primidone.	Approved, Vet Approved
Probenecid	The serum concentration of Leflunomide can be increased when it is combined with Probenecid.	Approved
Procarbazine	The risk or severity of adverse effects can be increased when Procarbazine is combined with Leflunomide.	Approved
Progesterone	The metabolism of Progesterone can be decreased when combined with Leflunomide.	Approved, Vet Approved
Proguanil	The metabolism of Proguanil can be decreased when combined with Leflunomide.	Approved
Promazine	The metabolism of Promazine can be decreased when combined with Leflunomide.	Approved, Vet Approved
Propacetamol	The risk or severity of adverse effects can be increased when Leflunomide is combined with Propacetamol.	Approved
Propofol	The metabolism of Propofol can be decreased when combined with Leflunomide.	Approved, Investigational, Vet Approved
Propranolol	Leflunomide may decrease the antihypertensive activities of Propranolol.	Approved, Investigational
Prostaglandin B2	The therapeutic efficacy of Prostaglandin B2 can be decreased when used in combination with Leflunomide.	Experimental
Prostaglandin G2	The therapeutic efficacy of Prostaglandin G2 can be decreased when used in combination with Leflunomide.	Experimental
Protein S human	Leflunomide may increase the anticoagulant activities of Protein S human.	Approved
Prulifloxacin	Leflunomide may increase the neuroexcitatory activities of Prulifloxacin.	Investigational
PTC299	The risk or severity of adverse effects can be increased when Leflunomide is combined with PTC299.	Investigational
Puromycin	Leflunomide may decrease the excretion rate of Puromycin which could result in a higher serum level.	Experimental
Pyrimethamine	The metabolism of Leflunomide can be decreased when combined with Pyrimethamine.	Approved, Vet Approved
Quazepam	The metabolism of Quazepam can be decreased when combined with Leflunomide.	Approved, Illicit
Quinapril	The risk or severity of adverse effects can be increased when Quinapril is combined with Leflunomide.	Approved, Investigational
Quinethazone	The therapeutic efficacy of Quinethazone can be decreased when used in combination with Leflunomide.	Approved
Quinidine	The metabolism of Quinidine can be decreased when combined with Leflunomide.	Approved
Quinine	The metabolism of Leflunomide can be decreased when combined with Quinine.	Approved
Ramipril	The risk or severity of adverse effects can be increased when Ramipril is combined with Leflunomide.	Approved
Rescinnamine	The risk or severity of adverse effects can be increased when Rescinnamine is combined with Leflunomide.	Approved
Resveratrol	The risk or severity of adverse effects can be increased when Leflunomide is combined with Resveratrol.	Experimental, Investigational
Reviparin	Leflunomide may increase the anticoagulant activities of Reviparin.	Approved
Ribostamycin	Leflunomide may decrease the excretion rate of Ribostamycin which could result in a higher serum level.	Approved
Rifampicin	The serum concentration of the active metabolites of Leflunomide can be increased when Leflunomide is used in combination with Rifampicin.	Approved
Rifapentine	The metabolism of Leflunomide can be increased when combined with Rifapentine.	Approved
Rilonacept	The risk or severity of adverse effects can be increased when Rilonacept is combined with Leflunomide.	Approved
Rimexolone	The risk or severity of adverse effects can be increased when Leflunomide is combined with Rimexolone.	Approved
Rindopepimut	The risk or severity of adverse effects can be increased when Leflunomide is combined with CDX-110.	Investigational
Risedronate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Risedronate.	Approved, Investigational
Rituximab	The risk or severity of adverse effects can be increased when Rituximab is combined with Leflunomide.	Approved
Rivaroxaban	Leflunomide may increase the anticoagulant activities of Rivaroxaban.	Approved
Rofecoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Rofecoxib.	Investigational, Withdrawn
Roflumilast	Roflumilast may increase the immunosuppressive activities of Leflunomide.	Approved
Rolapitant	The serum concentration of Leflunomide can be increased when it is combined with Rolapitant.	Approved
Ropinirole	The metabolism of Leflunomide can be decreased when combined with Ropinirole.	Approved, Investigational
Rosiglitazone	The metabolism of Rosiglitazone can be decreased when combined with Leflunomide.	Approved, Investigational
Rosoxacin	Leflunomide may increase the neuroexcitatory activities of Rosoxacin.	Approved
Rosuvastatin	The metabolism of Rosuvastatin can be decreased when combined with Leflunomide.	Approved
Ruxolitinib	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Leflunomide.	Approved
Sacubitril	The risk or severity of adverse effects can be increased when Sacubitril is combined with Leflunomide.	Approved
Salicylamide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Salicylamide.	Approved
Salicylic acid	The metabolism of Salicylic acid can be decreased when combined with Leflunomide.	Approved, Vet Approved
Salsalate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Salsalate.	Approved
Saprisartan	The risk or severity of adverse effects can be increased when Saprisartan is combined with Leflunomide.	Experimental
Secobarbital	The metabolism of Leflunomide can be increased when combined with Secobarbital.	Approved, Vet Approved
Secukinumab	The risk or severity of adverse effects can be increased when Secukinumab is combined with Leflunomide.	Approved
Selegiline	The metabolism of Selegiline can be decreased when combined with Leflunomide.	Approved, Investigational, Vet Approved
Seocalcitol	The risk or severity of adverse effects can be increased when Seocalcitol is combined with Leflunomide.	Experimental
Sertraline	The metabolism of Sertraline can be decreased when combined with Leflunomide.	Approved
Sildenafil	The metabolism of Leflunomide can be decreased when combined with Sildenafil.	Approved, Investigational
Siltuximab	The risk or severity of adverse effects can be increased when Siltuximab is combined with Leflunomide.	Approved
Simeprevir	The metabolism of Leflunomide can be decreased when combined with Simeprevir.	Approved
Sipuleucel-T	The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Leflunomide.	Approved
Sirolimus	The risk or severity of adverse effects can be increased when Sirolimus is combined with Leflunomide.	Approved, Investigational
Sisomicin	Leflunomide may decrease the excretion rate of Sisomicin which could result in a higher serum level.	Investigational
Sitaxentan	The metabolism of Sitaxentan can be decreased when combined with Leflunomide.	Approved, Investigational, Withdrawn
Sorafenib	The risk or severity of adverse effects can be increased when Sorafenib is combined with Leflunomide.	Approved, Investigational
Sotalol	Leflunomide may decrease the antihypertensive activities of Sotalol.	Approved
SP1049C	Leflunomide may decrease the excretion rate of SP1049C which could result in a higher serum level.	Investigational
Sparfloxacin	Leflunomide may increase the neuroexcitatory activities of Sparfloxacin.	Approved
Spectinomycin	Leflunomide may decrease the excretion rate of Spectinomycin which could result in a higher serum level.	Approved, Vet Approved
Spirapril	The risk or severity of adverse effects can be increased when Spirapril is combined with Leflunomide.	Approved
Spironolactone	Leflunomide may decrease the antihypertensive activities of Spironolactone.	Approved
SRP 299	The risk or severity of adverse effects can be increased when Leflunomide is combined with SRP 299.	Investigational
SRT501	The risk or severity of adverse effects can be increased when Leflunomide is combined with SRT501.	Investigational
Stepronin	The risk or severity of adverse effects can be increased when Stepronin is combined with Leflunomide.	Approved
Streptomycin	Leflunomide may decrease the excretion rate of Streptomycin which could result in a higher serum level.	Approved, Vet Approved
Streptozocin	The risk or severity of adverse effects can be increased when Streptozocin is combined with Leflunomide.	Approved
Sulfadiazine	The metabolism of Leflunomide can be decreased when combined with Sulfadiazine.	Approved, Vet Approved
Sulfamethoxazole	The metabolism of Leflunomide can be decreased when combined with Sulfamethoxazole.	Approved
Sulfamoxole	The metabolism of Sulfamoxole can be decreased when combined with Leflunomide.	Approved
Sulfasalazine	Leflunomide may increase the nephrotoxic activities of Sulfasalazine.	Approved
Sulfinpyrazone	The metabolism of Sulfinpyrazone can be decreased when combined with Leflunomide.	Approved
Sulfisoxazole	The metabolism of Leflunomide can be decreased when combined with Sulfisoxazole.	Approved, Vet Approved
Sulindac	The risk or severity of adverse effects can be increased when Sulindac is combined with Leflunomide.	Approved
Sulodexide	Leflunomide may increase the anticoagulant activities of Sulodexide.	Approved, Investigational
Sulprostone	The therapeutic efficacy of Sulprostone can be decreased when used in combination with Leflunomide.	Investigational
Sunitinib	The risk or severity of adverse effects can be increased when Sunitinib is combined with Leflunomide.	Approved, Investigational
Suprofen	The metabolism of Suprofen can be decreased when combined with Leflunomide.	Approved, Withdrawn
Tacrolimus	The risk or severity of adverse effects can be increased when Tacrolimus is combined with Leflunomide.	Approved, Investigational
Tacrolimus	Leflunomide may increase the nephrotoxic activities of Tacrolimus.	Approved, Investigational
Tafluprost	The therapeutic efficacy of Tafluprost can be decreased when used in combination with Leflunomide.	Approved
Talniflumate	The risk or severity of adverse effects can be increased when Talniflumate is combined with Leflunomide.	Approved
Tamoxifen	The metabolism of Tamoxifen can be decreased when combined with Leflunomide.	Approved
Tapentadol	The metabolism of Tapentadol can be decreased when combined with Leflunomide.	Approved
Tasosartan	The risk or severity of adverse effects can be increased when Tasosartan is combined with Leflunomide.	Approved
Technetium Tc-99m medronate	The risk or severity of adverse effects can be increased when Leflunomide is combined with Technetium Tc-99m Medronate.	Approved
Telmisartan	The risk or severity of adverse effects can be increased when Telmisartan is combined with Leflunomide.	Approved, Investigational
Temafloxacin	Leflunomide may increase the neuroexcitatory activities of Temafloxacin.	Withdrawn
Temazepam	The metabolism of Temazepam can be decreased when combined with Leflunomide.	Approved
Temocapril	The risk or severity of adverse effects can be increased when Temocapril is combined with Leflunomide.	Experimental, Investigational
Temozolomide	The risk or severity of adverse effects can be increased when Temozolomide is combined with Leflunomide.	Approved, Investigational
Temsirolimus	The risk or severity of adverse effects can be increased when Temsirolimus is combined with Leflunomide.	Approved
Teniposide	The risk or severity of adverse effects can be increased when Teniposide is combined with Leflunomide.	Approved
Tenofovir disoproxil	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tenofovir.	Approved, Investigational
Tenoxicam	The metabolism of Tenoxicam can be decreased when combined with Leflunomide.	Approved
Terbinafine	The metabolism of Terbinafine can be decreased when combined with Leflunomide.	Approved, Investigational, Vet Approved
Terfenadine	The metabolism of Terfenadine can be decreased when combined with Leflunomide.	Withdrawn
Teriflunomide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Teriflunomide.	Approved
Testosterone	The metabolism of Testosterone can be decreased when combined with Leflunomide.	Approved, Investigational
Thalidomide	The risk or severity of adverse effects can be increased when Thalidomide is combined with Leflunomide.	Approved, Investigational, Withdrawn
Theophylline	The metabolism of Leflunomide can be decreased when combined with Theophylline.	Approved
Thiamylal	The metabolism of Thiamylal can be decreased when combined with Leflunomide.	Approved, Vet Approved
Thiotepa	The risk or severity of adverse effects can be increased when Thiotepa is combined with Leflunomide.	Approved
Tiaprofenic acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tiaprofenic acid.	Approved
Ticagrelor	The metabolism of Leflunomide can be decreased when combined with Ticagrelor.	Approved
Ticlopidine	The metabolism of Leflunomide can be decreased when combined with Ticlopidine.	Approved
Tiludronic acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tiludronate.	Approved, Vet Approved
Timolol	Leflunomide may decrease the antihypertensive activities of Timolol.	Approved
Tinoridine	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tinoridine.	Investigational
Tioguanine	The risk or severity of adverse effects can be increased when Tioguanine is combined with Leflunomide.	Approved
Tixocortol	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tixocortol.	Approved
Tobramycin	Leflunomide may decrease the excretion rate of Tobramycin which could result in a higher serum level.	Approved, Investigational
Tocilizumab	The risk or severity of adverse effects can be increased when Tocilizumab is combined with Leflunomide.	Approved
Tofacitinib	Leflunomide may increase the immunosuppressive activities of Tofacitinib.	Approved, Investigational
Tolbutamide	The serum concentration of Tolbutamide can be increased when it is combined with Leflunomide.	Approved
Tolfenamic Acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tolfenamic Acid.	Approved
Tolmetin	The risk or severity of adverse effects can be increased when Tolmetin is combined with Leflunomide.	Approved
Tolterodine	The metabolism of Tolterodine can be decreased when combined with Leflunomide.	Approved, Investigational
Topotecan	The risk or severity of adverse effects can be increased when Topotecan is combined with Leflunomide.	Approved, Investigational
Torasemide	Leflunomide may decrease the diuretic activities of Torasemide.	Approved
Tositumomab	The risk or severity of adverse effects can be increased when Tositumomab is combined with Leflunomide.	Approved
Trabectedin	The risk or severity of adverse effects can be increased when Trabectedin is combined with Leflunomide.	Approved, Investigational
Trandolapril	The risk or severity of adverse effects can be increased when Trandolapril is combined with Leflunomide.	Approved
Tranilast	The risk or severity of adverse effects can be increased when Leflunomide is combined with Tranilast.	Approved, Investigational
Trastuzumab	Trastuzumab may increase the cardiotoxic activities of Leflunomide.	Approved, Investigational
Trastuzumab emtansine	The risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Leflunomide.	Approved
Travoprost	The therapeutic efficacy of Travoprost can be decreased when used in combination with Leflunomide.	Approved
Treprostinil	The risk or severity of adverse effects can be increased when Treprostinil is combined with Leflunomide.	Approved, Investigational
Tretinoin	The risk or severity of adverse effects can be increased when Tretinoin is combined with Leflunomide.	Approved, Investigational, Nutraceutical
Triamcinolone	The risk or severity of adverse effects can be increased when Triamcinolone is combined with Leflunomide.	Approved, Vet Approved
Triamterene	Leflunomide may decrease the antihypertensive activities of Triamterene.	Approved
Trichlormethiazide	The therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Leflunomide.	Approved, Vet Approved
Trimethadione	The metabolism of Trimethadione can be decreased when combined with Leflunomide.	Approved
Trimethoprim	The metabolism of Leflunomide can be decreased when combined with Trimethoprim.	Approved, Vet Approved
Trimipramine	The metabolism of Trimipramine can be decreased when combined with Leflunomide.	Approved
Trofosfamide	The risk or severity of adverse effects can be increased when Trofosfamide is combined with Leflunomide.	Investigational
Troglitazone	The metabolism of Troglitazone can be decreased when combined with Leflunomide.	Withdrawn
Trovafloxacin	Leflunomide may increase the neuroexcitatory activities of Trovafloxacin.	Approved, Withdrawn
Unoprostone	The therapeutic efficacy of Unoprostone can be decreased when used in combination with Leflunomide.	Approved
Ustekinumab	The risk or severity of adverse effects can be increased when Ustekinumab is combined with Leflunomide.	Approved, Investigational
Valdecoxib	The risk or severity of adverse effects can be increased when Leflunomide is combined with Valdecoxib.	Investigational, Withdrawn
Valproic Acid	The metabolism of Leflunomide can be decreased when combined with Valproic Acid.	Approved, Investigational
Valrubicin	Leflunomide may decrease the excretion rate of Valrubicin which could result in a higher serum level.	Approved
Valsartan	The metabolism of Leflunomide can be decreased when combined with Valsartan.	Approved, Investigational
Vancomycin	The serum concentration of Vancomycin can be increased when it is combined with Leflunomide.	Approved
Vedolizumab	The risk or severity of adverse effects can be increased when Vedolizumab is combined with Leflunomide.	Approved
Vemurafenib	The serum concentration of Leflunomide can be increased when it is combined with Vemurafenib.	Approved
Venlafaxine	The metabolism of Venlafaxine can be decreased when combined with Leflunomide.	Approved
Verapamil	The metabolism of Verapamil can be decreased when combined with Leflunomide.	Approved
Vilanterol	The risk or severity of adverse effects can be increased when Vilanterol is combined with Leflunomide.	Approved
Vinblastine	The risk or severity of adverse effects can be increased when Vinblastine is combined with Leflunomide.	Approved
Vincristine	The risk or severity of adverse effects can be increased when Vincristine is combined with Leflunomide.	Approved, Investigational
Vindesine	The risk or severity of adverse effects can be increased when Vindesine is combined with Leflunomide.	Approved
Vinorelbine	The risk or severity of adverse effects can be increased when Vinorelbine is combined with Leflunomide.	Approved, Investigational
Vismodegib	The metabolism of Vismodegib can be decreased when combined with Leflunomide.	Approved
Voclosporin	The risk or severity of adverse effects can be increased when Lx211 is combined with Leflunomide.	Investigational
Voriconazole	The metabolism of Leflunomide can be decreased when combined with Voriconazole.	Approved, Investigational
Vortioxetine	The metabolism of Vortioxetine can be decreased when combined with Leflunomide.	Approved
Warfarin	Leflunomide may increase the anticoagulant activities of Warfarin.	Approved
Ximelagatran	The metabolism of Ximelagatran can be decreased when combined with Leflunomide.	Approved, Investigational, Withdrawn
Zafirlukast	The metabolism of Leflunomide can be decreased when combined with Zafirlukast.	Approved, Investigational
Zalcitabine	The metabolism of Zalcitabine can be decreased when combined with Leflunomide.	Approved
Zaltoprofen	The metabolism of Zaltoprofen can be decreased when combined with Leflunomide.	Approved
Zidovudine	The metabolism of Zidovudine can be decreased when combined with Leflunomide.	Approved
Zileuton	The metabolism of Zileuton can be decreased when combined with Leflunomide.	Approved, Investigational, Withdrawn
Zoledronic acid	The risk or severity of adverse effects can be increased when Leflunomide is combined with Zoledronic acid.	Approved
Zolpidem	The metabolism of Zolpidem can be decreased when combined with Leflunomide.	Approved
Zomepirac	The risk or severity of adverse effects can be increased when Leflunomide is combined with Zomepirac.	Withdrawn
Zopiclone	The metabolism of Zopiclone can be decreased when combined with Leflunomide.	Approved
Zorubicin	Leflunomide may decrease the excretion rate of Zorubicin which could result in a higher serum level.	Experimental

Food Interactions

Take without regard to meals.

References

Synthesis Reference

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

US20010031878

General References

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 ]
Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743 ]
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 ]
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 ]
Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033 ]
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 ]
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 ]
Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414 ]

External Links

Resource	Link
Human Metabolome Database (HMDB)	HMDB15229
KEGG Drug	D00749
KEGG Compound	C07905
PubChem Compound	3899
PubChem Substance	46506013
ChemSpider	3762
BindingDB	50054601
ChEBI	6402
ChEMBL	CHEMBL960
Therapeutic Targets Database	DAP000636
PharmGKB	PA450192
Drug Product Database	11980
RxList	http://www.rxlist.com/cgi/generic3/leflunomide.htm
Drugs.com	http://www.drugs.com/cdi/leflunomide.html
Wikipedia	Leflunomide

ATC Codes

L04AA13 — Leflunomide

AHFS Codes

92:00.00

PDB Entries

1D3H

FDA label

Download (1.23 MB)

MSDS

Download (105 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	2
1	Completed	Not Available	To Determine Bioequivalence Under Fed Conditions	1
1	Completed	Not Available	To Determine the Bioequivalence Study Under Fasting	1
1	Completed	Treatment	Gliomas / Sarcomas	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
1	Completed	Treatment	Psoriatic Arthritis / Rheumatoid Arthritis	1
1	Terminated	Treatment	Melanoma	1
1, 2	Recruiting	Treatment	Recurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma	1
2	Completed	Treatment	Adult-Onset Still's Disease	1
2	Completed	Treatment	Brain and Central Nervous System Tumors	1
2	Completed	Treatment	Rheumatoid Arthritis	1
2	Completed	Treatment	Systemic Lupus Eythematosus (SLE)	1
2	Completed	Treatment	Uveitis	1
2	Recruiting	Prevention	Viral sepsis / Viruria	1
2	Recruiting	Treatment	Henoch-Schoenlein Purpura Nephritis	1
2	Unknown Status	Treatment	Bullous Pemphigoid (BP)	1
2	Withdrawn	Treatment	Systemic Lupus Erythematosus (SLE)	1
2, 3	Completed	Treatment	Malignant Neoplasm of Prostate	1
3	Active Not Recruiting	Treatment	Rheumatoid Arthritis	1
3	Completed	Treatment	Brain and Central Nervous System Tumors	1
3	Completed	Treatment	Rheumatoid Arthritis	6
3	Terminated	Treatment	Nephritis, Lupus	1
3	Unknown Status	Treatment	Myasthenia Gravis	1
4	Completed	Treatment	Rheumatoid Arthritis	5
4	Enrolling by Invitation	Basic Science	Rheumatoid Arthritis	1
4	Recruiting	Treatment	Immunoglobulin G4 Related Sclerosing Disease	1
4	Recruiting	Treatment	Rheumatoid Arthritis	1
4	Terminated	Treatment	Rheumatoid Arthritis	1
4	Unknown Status	Treatment	Juvenile Idiopathic Arthritis (JIA)	1
4	Unknown Status	Treatment	Rheumatoid Arthritis	1
Not Available	Completed	Basic Science	Rheumatoid Arthritis	1
Not Available	Completed	Treatment	Rheumatoid Arthritis	1
Not Available	Recruiting	Treatment	Lupus / Nephritis	1
Not Available	Unknown Status	Treatment	BK Virus Infection / Terminal Renal Failure	1
Not Available	Unknown Status	Treatment	Rheumatoid Arthritis	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Apotex Inc.
Barr Pharmaceuticals
Diversified Healthcare Services Inc.
Heritage Pharmaceuticals
Kali Laboratories Inc.
Murfreesboro Pharmaceutical Nursing Supply
Physicians Total Care Inc.
Prasco Labs
Sandoz
Sanofi-Aventis Inc.
Teva Pharmaceutical Industries Ltd.

Dosage forms

Form	Route	Strength
Tablet, film coated	Oral	10 mg/1
Tablet, film coated	Oral	10 mg
Tablet, film coated	Oral	100 mg
Tablet, film coated	Oral	100 mg/1
Tablet, film coated	Oral	20 mg
Tablet, film coated	Oral	20 mg/1
Tablet	Oral	100 mg
Tablet	Oral	10 mg
Tablet	Oral	20 mg
Tablet	Oral	10 mg/1
Tablet	Oral	20 mg/1
Tablet, film coated	Oral	15 mg

Prices

Unit description	Cost	Unit
Arava 10 mg tablet	24.76USD	tablet
Arava 20 mg tablet	24.76USD	tablet
Leflunomide 10 mg tablet	16.75USD	tablet
Leflunomide 20 mg tablet	16.75USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	165-166 °C	Not Available
water solubility	21 mg/L (poorly soluble)	Not Available
logP	2.8	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0844 mg/mL	ALOGPS
logP	2.52	ALOGPS
logP	2.51	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	10.41	ChemAxon
pKa (Strongest Basic)	-0.45	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	55.13 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	64.16 m³·mol^-1	ChemAxon
Polarizability	23.11 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9949
Caco-2 permeable	+	0.5069
P-glycoprotein substrate	Non-substrate	0.909
P-glycoprotein inhibitor I	Non-inhibitor	0.7822
P-glycoprotein inhibitor II	Non-inhibitor	0.8889
Renal organic cation transporter	Non-inhibitor	0.9154
CYP450 2C9 substrate	Non-substrate	0.8548
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.5211
CYP450 1A2 substrate	Inhibitor	0.9189
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Non-inhibitor	0.5117
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.5622
Ames test	Non AMES toxic	0.5504
Carcinogenicity	Non-carcinogens	0.7067
Biodegradation	Not ready biodegradable	0.9836
Rat acute toxicity	3.0297 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9879
hERG inhibition (predictor II)	Non-inhibitor	0.9068

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-00di-0390000000-1ac4065d1ef245442a16	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-03di-2920000000-819d0674f452a60be1a4	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Anilides

Direct Parent

Aromatic anilides

Alternative Parents

Trifluoromethylbenzenes / Isoxazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organofluorides

Substituents

Aromatic anilide / Trifluoromethylbenzene / Azole / Isoxazole / Heteroaromatic compound / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid derivative / Organoheterocyclic compound / Azacycle

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

monocarboxylic acid amide, isoxazoles, (trifluoromethyl)benzenes (CHEBI:6402 )

Targets

Details

1. Dihydroorotate dehydrogenase (quinone), mitochondrial

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
Uniprot Name:: Dihydroorotate dehydrogenase (quinone), mitochondrial
Molecular Weight:: 42866.93 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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 ]
Prakash A, Jarvis B: Leflunomide: a review of its use in active rheumatoid arthritis. Drugs. 1999 Dec;58(6):1137-64. [PubMed:10651393 ]
Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743 ]
Wozel G, Pfeiffer C: [Leflunomide--a new drug for pharmacological immunomodulation]. Hautarzt. 2002 May;53(5):309-15. [PubMed:12063741 ]
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 ]
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 ]
Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033 ]
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 ]
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 ]
Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414 ]
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 ]

Details

2. Aryl hydrocarbon receptor

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
Uniprot Name:: Aryl hydrocarbon receptor
Molecular Weight:: 96146.705 Da

References

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 ]
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 ]

Details

3. Protein-tyrosine kinase 2-beta

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
Uniprot Name:: Protein-tyrosine kinase 2-beta
Molecular Weight:: 115873.62 Da

References

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 ]
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 ]
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

Details

1. Cytochrome P450 2C9

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
Uniprot Name:: Cytochrome P450 2C9
Molecular Weight:: 55627.365 Da

References

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 ]
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 ]

Details

2. Cytochrome P450 1A2

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
Uniprot Name:: Cytochrome P450 1A2
Molecular Weight:: 58293.76 Da

References

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 ]
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

Details

1. ATP-binding cassette sub-family G member 2

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
Uniprot Name:: ATP-binding cassette sub-family G member 2
Molecular Weight:: 72313.47 Da

References

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 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:56

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Structure for DB01097 (Leflunomide)

Targets

References

References

References

Enzymes

References

References

Transporters

References