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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- 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
Structure for DB01097 (Leflunomide)
- 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
- Leflunomida
- Leflunomide
- Leflunomidum
- Lefunomide
- External IDs
- L04AA13 / SU-101 / SU101
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Arava Tablet, film coated 20 mg/1 Oral bryant ranch prepack 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/1 Oral Sanofi Aventis 1998-09-10 Not applicable US Arava Tablet, film coated 100 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 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 - 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 Dom-leflunomide Tablet 20 mg Oral Dominion Pharmacal Not applicable Not applicable Canada Dom-leflunomide Tablet 10 mg Oral Dominion Pharmacal Not applicable Not applicable Canada Leflunomide Tablet 10 mg/1 Oral Alembic Pharmaceuticals Limited 2016-12-01 Not applicable US Leflunomide Tablet 20 mg/1 Oral Alembic Pharmaceuticals Limited 2016-12-01 Not applicable US Leflunomide Tablet, film coated 20 mg/1 Oral Physicians Total Care, Inc. 2006-07-10 Not applicable US Leflunomide Tablet 10 mg/1 Oral Trigen Laboratories, Inc. 2011-05-06 Not applicable US Leflunomide Tablet, film coated 10 mg/1 Oral Teva 2005-09-14 2015-10-31 US 
Leflunomide Tablet, film coated 20 mg/1 Oral Prasco, Laboratories 1998-09-10 2017-11-29 US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU - International/Other Brands
- Arava
- 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.
- Associated Conditions
- 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 Actions Organism ADihydroorotate dehydrogenase (quinone), mitochondrial inhibitorHuman UAryl hydrocarbon receptor agonistHuman UProtein-tyrosine kinase 2-beta antagonistHuman - 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.
- 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 The presence of this genotype in CYP1A2 may be associated with an increased risk of drug-related toxicity from leflunomide therapy. Details
Interactions
- Drug Interactions
Drug Interaction Drug group (4R)-limonene The risk or severity of adverse effects can be increased when Leflunomide is combined with (4R)-limonene. Investigational 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 Abetimus The risk or severity of adverse effects can be increased when Abetimus is combined with Leflunomide. Investigational 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, Investigational Aceclofenac The risk or severity of adverse effects can be increased when Leflunomide is combined with Aceclofenac. Approved, Investigational Acemetacin The risk or severity of adverse effects can be increased when Leflunomide is combined with Acemetacin. Approved, Experimental, Investigational Acenocoumarol Leflunomide may increase the anticoagulant activities of Acenocoumarol. Approved, Investigational Acetyl sulfisoxazole The metabolism of Leflunomide can be decreased when combined with Acetyl sulfisoxazole. Approved, Vet Approved Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Leflunomide. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Leflunomide. Experimental Acetylsalicylic acid The risk or severity of adverse effects can be increased when Leflunomide is combined with Acetylsalicylic acid. Approved, Vet Approved 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 The risk or severity of adverse effects can be increased when Adefovir is combined with Leflunomide. Investigational Afelimomab The risk or severity of adverse effects can be increased when Afelimomab is combined with Leflunomide. Investigational Alclofenac The risk or severity of adverse effects can be increased when Leflunomide is combined with Alclofenac. Approved, Withdrawn 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, Investigational Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Leflunomide. Approved, Investigational, 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 Alicaforsen The risk or severity of adverse effects can be increased when Alicaforsen is combined with Leflunomide. Investigational Aliskiren Leflunomide may decrease the antihypertensive activities of Aliskiren. Approved, Investigational Alminoprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Alminoprofen. Experimental 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 Amiloride Leflunomide may decrease the antihypertensive activities of Amiloride. Approved Aminophenazone The metabolism of Aminophenazone can be decreased when combined with Leflunomide. Approved, Withdrawn Aminosalicylic Acid The risk or severity of adverse effects can be increased when Leflunomide is combined with Aminosalicylic Acid. Approved 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, Investigational Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Leflunomide. Approved, Investigational Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide. Approved Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Leflunomide. Approved, Investigational, Withdrawn Ancrod Leflunomide may increase the anticoagulant activities of Ancrod. Approved, Investigational Andrographolide The risk or severity of adverse effects can be increased when Leflunomide is combined with Andrographolide. Investigational Androstenedione The risk or severity of adverse effects can be increased when Leflunomide is combined with Androstenedione. Experimental, Illicit Anecortave The risk or severity of adverse effects can be increased when Leflunomide is combined with Anecortave. Investigational anecortave acetate The risk or severity of adverse effects can be increased when Leflunomide is combined with anecortave acetate. Investigational Anisodamine The risk or severity of adverse effects can be increased when Leflunomide is combined with Anisodamine. Investigational Anthrax immune globulin human The risk or severity of adverse effects can be increased when Leflunomide is combined with Anthrax immune globulin human. Approved Antilymphocyte immunoglobulin (horse) The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Leflunomide. Approved, Investigational Antipyrine The risk or severity of adverse effects can be increased when Leflunomide is combined with Antipyrine. Approved, Investigational 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 Antithymocyte immunoglobulin (rabbit) is combined with Leflunomide. Approved Antrafenine The risk or severity of adverse effects can be increased when Leflunomide is combined with Antrafenine. Approved Apalutamide The serum concentration of Leflunomide can be decreased when it is combined with Apalutamide. Approved, Investigational 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 Apocynin. 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, Investigational Ardeparin Leflunomide may increase the anticoagulant activities of Ardeparin. Approved, Investigational, 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. Investigational Artemether The metabolism of Artemether can be decreased when combined with Leflunomide. Approved Asenapine Leflunomide may decrease the antihypertensive activities of Asenapine. Approved Asunaprevir The metabolism of Asunaprevir can be decreased when combined with Leflunomide. Approved, Investigational, Withdrawn Atamestane The risk or severity of adverse effects can be increased when Leflunomide is combined with Atamestane. Investigational Atazanavir The metabolism of Atazanavir can be decreased when combined with Leflunomide. Approved, Investigational Atenolol Leflunomide may decrease the antihypertensive activities of Atenolol. Approved Avatrombopag The metabolism of Avatrombopag can be decreased when combined with Leflunomide. Approved, Investigational 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 Azficel-T The risk or severity of adverse effects can be increased when Leflunomide is combined with Azficel-T. Approved, Investigational Azilsartan medoxomil The risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Leflunomide. Approved, Investigational Azithromycin The metabolism of Leflunomide can be decreased when combined with Azithromycin. Approved Azosemide The therapeutic efficacy of Azosemide can be decreased when used in combination with Leflunomide. Investigational Bacillus calmette-guerin substrain connaught live antigen The risk or severity of adverse effects can be increased when Leflunomide is combined with Bacillus calmette-guerin substrain connaught live antigen. Approved, Investigational Bacillus calmette-guerin substrain tice live antigen The risk or severity of adverse effects can be increased when Leflunomide is combined with Bacillus calmette-guerin substrain tice live antigen. Approved Balsalazide The risk or severity of adverse effects can be increased when Leflunomide is combined with 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 risk or severity of adverse effects can be increased when Leflunomide is combined with BCG vaccine. 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 Begelomab The risk or severity of adverse effects can be increased when Begelomab is combined with Leflunomide. Experimental, Investigational Bekanamycin Leflunomide may decrease the excretion rate of Bekanamycin which could result in a higher serum level. Experimental Belatacept The risk or severity of adverse effects can be increased when Belatacept is combined with Leflunomide. Approved, Investigational 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 Leflunomide is combined with Benazepril. Approved, Investigational Bendazac The risk or severity of adverse effects can be increased when Leflunomide is combined with Bendazac. Experimental Bendroflumethiazide The therapeutic efficacy of Bendroflumethiazide can be decreased when used in combination with Leflunomide. Approved Benorilate The risk or severity of adverse effects can be increased when Leflunomide is combined with Benorilate. Experimental 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. Approved, Investigational Benzthiazide The therapeutic efficacy of Benzthiazide can be decreased when used in combination with Leflunomide. Approved Benzydamine The risk or severity of adverse effects can be increased when Leflunomide is combined with Benzydamine. Approved 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, Investigational Betrixaban The risk or severity of bleeding can be increased when Betrixaban is combined with Leflunomide. Approved, Investigational Bevacizumab Bevacizumab may increase the cardiotoxic activities of Leflunomide. Approved, Investigational Bevantolol Leflunomide may decrease the antihypertensive activities of Bevantolol. Approved Bevonium The risk or severity of adverse effects can be increased when Leflunomide is combined with Bevonium. Experimental 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, Investigational Blinatumomab The risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide. Approved, Investigational 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, Investigational Briakinumab The risk or severity of adverse effects can be increased when Briakinumab is combined with Leflunomide. Investigational Brivaracetam The metabolism of Brivaracetam can be decreased when combined with Leflunomide. Approved, Investigational Brodalumab The risk or severity of adverse effects can be increased when Brodalumab is combined with Leflunomide. Approved, Investigational Bromfenac The risk or severity of adverse effects can be increased when Leflunomide is combined with Bromfenac. 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 Leflunomide is combined with Budesonide. Approved Bufexamac The risk or severity of adverse effects can be increased when Leflunomide is combined with Bufexamac. Approved, Experimental Bufuralol Leflunomide may decrease the antihypertensive activities of Bufuralol. Experimental, Investigational Bumadizone The risk or severity of adverse effects can be increased when Leflunomide is combined with Bumadizone. Experimental Bumetanide The therapeutic efficacy of Bumetanide can be decreased when used in combination with Leflunomide. 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 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, Investigational 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. Experimental Candesartan cilexetil The metabolism of Candesartan cilexetil can be decreased when combined with Leflunomide. Approved Candoxatril The risk or severity of adverse effects can be increased when Leflunomide is combined with Candoxatril. Experimental Cannabidiol The metabolism of Cannabidiol can be decreased when combined with Leflunomide. Approved, Investigational Capecitabine The risk or severity of adverse effects can be increased when Capecitabine is combined with Leflunomide. Approved, Investigational Capsaicin The risk or severity of adverse effects can be increased when Leflunomide is combined with Capsaicin. Approved Captopril The risk or severity of adverse effects can be increased when Leflunomide is combined with Captopril. Approved Carbamazepine The risk or severity of adverse effects can be increased when Leflunomide is combined with Carbamazepine. Approved, Investigational Carbaspirin calcium The risk or severity of adverse effects can be increased when Leflunomide is combined with Carbaspirin calcium. Experimental, 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, Investigational Carprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Carprofen. Approved, Vet Approved, Withdrawn Carteolol Leflunomide may decrease the antihypertensive activities of Carteolol. Approved 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, Investigational 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, Investigational, Vet Approved Chlorothiazide The therapeutic efficacy of Chlorothiazide can be decreased when used in combination with Leflunomide. Approved, Vet Approved Chlorphenesin The risk or severity of adverse effects can be increased when Leflunomide is combined with Chlorphenesin. Approved, Vet Approved, Withdrawn Chlorpropamide The metabolism of Chlorpropamide can be decreased when combined with Leflunomide. Approved, Investigational 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, Investigational Choline magnesium trisalicylate The risk or severity of adverse effects can be increased when Leflunomide is combined with Choline magnesium trisalicylate. 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 Leflunomide is combined with Cilazapril. Approved Cimicoxib The risk or severity of adverse effects can be increased when Leflunomide is combined with Cimicoxib. Investigational Cinoxacin Leflunomide may increase the neuroexcitatory activities of Cinoxacin. Approved, Investigational, Withdrawn 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 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. Approved, Investigational Clobetasol propionate The risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasol propionate. Approved Clobetasone The risk or severity of adverse effects can be increased when Leflunomide is combined with Clobetasone. 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 Clodronic Acid. 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 Cloprostenol The therapeutic efficacy of Cloprostenol can be decreased when used in combination with Leflunomide. Vet Approved Cloranolol Leflunomide may decrease the antihypertensive activities of Cloranolol. Experimental Clorindione Leflunomide may increase the anticoagulant activities of Clorindione. Experimental Clostridium tetani toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Leflunomide is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated). 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 Cortexolone 17α-propionate The risk or severity of adverse effects can be increased when Leflunomide is combined with Cortexolone 17α-propionate. Investigational Corticosterone The risk or severity of adverse effects can be increased when Leflunomide is combined with Corticosterone. Experimental Corticotropin The risk or severity of adverse effects can be increased when Corticotropin is combined with Leflunomide. Approved, Investigational, Vet Approved Cortisone acetate The risk or severity of adverse effects can be increased when Cortisone acetate is combined with Leflunomide. Approved, Investigational Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Leflunomide is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). Approved Crisaborole The metabolism of Leflunomide can be decreased when combined with Crisaborole. Approved, Investigational Curcumin The metabolism of Leflunomide can be decreased when combined with Curcumin. Approved, Investigational Cyclopenthiazide The therapeutic efficacy of Cyclopenthiazide can be decreased when used in combination with Leflunomide. Experimental 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 Cymarin Cymarin may decrease the cardiotoxic activities of Leflunomide. Experimental 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, Investigational 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. Investigational, Withdrawn Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Leflunomide. Approved, Investigational Dalteparin Leflunomide may increase the anticoagulant activities of Dalteparin. Approved Danaparoid Leflunomide may increase the anticoagulant activities of Danaparoid. Approved, Withdrawn Dapsone The metabolism of Dapsone can be decreased when combined with Leflunomide. Approved, Investigational Darexaban Leflunomide may increase the anticoagulant activities of Darexaban. 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 Deflazacort The risk or severity of adverse effects can be increased when Deflazacort is combined with Leflunomide. Approved, Investigational Delapril The risk or severity of adverse effects can be increased when Leflunomide is combined with Delapril. 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 Desipramine Leflunomide may decrease the antihypertensive activities of Desipramine. Approved, 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 Desonide The risk or severity of adverse effects can be increased when Leflunomide is combined with Desonide. Approved, Investigational Desoximetasone The risk or severity of adverse effects can be increased when Leflunomide is combined with Desoximetasone. Approved Desoxycorticosterone acetate The risk or severity of adverse effects can be increased when Leflunomide is combined with Desoxycorticosterone acetate. 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 Leflunomide is combined with Dexamethasone. Approved, Investigational, Vet Approved Dexamethasone isonicotinate The risk or severity of adverse effects can be increased when Leflunomide is combined with Dexamethasone isonicotinate. Vet Approved Dexibuprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Dexibuprofen. Approved, Investigational Dexketoprofen The risk or severity of adverse effects can be increased when Dexketoprofen is combined with Leflunomide. Approved, Investigational Dextran Leflunomide may increase the anticoagulant activities of Dextran. Approved, Investigational, Vet Approved Diazepam The metabolism of Diazepam can be decreased when combined with Leflunomide. Approved, Illicit, Investigational, Vet Approved Dibekacin Leflunomide may decrease the excretion rate of Dibekacin which could result in a higher serum level. Experimental Dibotermin alfa The risk or severity of adverse effects can be increased when Leflunomide is combined with Dibotermin alfa. Approved, Investigational Dicoumarol Leflunomide may increase the anticoagulant activities of Dicoumarol. Approved Difenpiramide The risk or severity of adverse effects can be increased when Leflunomide is combined with Difenpiramide. Experimental 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 Leflunomide is combined with Diflunisal. Approved, Investigational Difluocortolone The risk or severity of adverse effects can be increased when Leflunomide is combined with Difluocortolone. Approved, Investigational, Withdrawn 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, Investigational Digoxin The serum concentration of Digoxin can be increased when it is combined with Leflunomide. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Leflunomide. Approved Dihydrostreptomycin Leflunomide may decrease the excretion rate of Dihydrostreptomycin which could result in a higher serum level. Investigational, Vet 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, Investigational Diphenadione Leflunomide may increase the anticoagulant activities of Diphenadione. Experimental Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Leflunomide. Approved, Investigational Doconexent The metabolism of Doconexent can be decreased when combined with Leflunomide. Approved, Investigational Dolasetron The metabolism of Dolasetron can be decreased when combined with Leflunomide. Approved, Investigational 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 Dosulepin The metabolism of Leflunomide can be decreased when combined with Dosulepin. Approved Doxepin The metabolism of Doxepin can be decreased when combined with Leflunomide. Approved, Investigational 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. Withdrawn 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 E-6201. 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 Leflunomide is combined with Enalapril. Approved, Vet Approved Enalaprilat The risk or severity of adverse effects can be increased when Leflunomide is combined with Enalaprilat. Approved Enasidenib The metabolism of Enasidenib can be decreased when combined with Leflunomide. Approved, Investigational Enoxacin Leflunomide may increase the neuroexcitatory activities of Enoxacin. Approved, Investigational Enoxaparin Leflunomide may increase the anticoagulant activities of Enoxaparin. Approved Enprostil The therapeutic efficacy of Enprostil can be decreased when used in combination with Leflunomide. Experimental Epanolol Leflunomide may decrease the antihypertensive activities of Epanolol. Experimental 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 Epitizide The therapeutic efficacy of Epitizide can be decreased when used in combination with Leflunomide. Experimental 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 Esatenolol Leflunomide may decrease the antihypertensive activities of Esatenolol. Experimental Esmolol Leflunomide may decrease the antihypertensive activities of Esmolol. Approved Estradiol The serum concentration of Leflunomide can be increased when it is combined with Estradiol. Approved, Investigational, Vet Approved Estradiol acetate The metabolism of Estradiol acetate can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Estradiol benzoate The metabolism of Estradiol benzoate can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Estradiol cypionate The metabolism of Estradiol cypionate can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Estradiol dienanthate The metabolism of Estradiol dienanthate can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Estradiol valerate The metabolism of Estradiol valerate 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, Investigational 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, Investigational Etacrynic acid The therapeutic efficacy of Etacrynic acid can be decreased when used in combination with Leflunomide. Approved, Investigational Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Leflunomide. Approved, Investigational Ethenzamide The risk or severity of adverse effects can be increased when Leflunomide is combined with Ethenzamide. Experimental 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, Investigational 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 Leflunomide can be decreased when combined with Etravirine. Approved Evening primrose oil The risk or severity of adverse effects can be increased when Leflunomide is combined with Evening primrose oil. Investigational, Nutraceutical Everolimus The risk or severity of adverse effects can be increased when Leflunomide is combined with Everolimus. Approved Exisulind The risk or severity of adverse effects can be increased when Leflunomide is combined with Exisulind. Investigational Felbinac The risk or severity of adverse effects can be increased when Leflunomide is combined with Felbinac. Experimental Fenbufen The risk or severity of adverse effects can be increased when Leflunomide is combined with Fenbufen. Approved Fenofibric acid The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Leflunomide is combined with Fenofibric acid. Approved Fenoprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Fenoprofen. Approved Fenprostalene The therapeutic efficacy of Fenprostalene can be decreased when used in combination with Leflunomide. Vet Approved Fentiazac The risk or severity of adverse effects can be increased when Leflunomide is combined with Fentiazac. Experimental Feprazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Feprazone. Experimental Ferulic acid Leflunomide may increase the anticoagulant activities of Ferulic acid. Experimental Fimasartan The risk or severity of adverse effects can be increased when Fimasartan is combined with Leflunomide. Approved, Investigational 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 Fluasterone The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluasterone. Investigational Fluconazole The metabolism of Leflunomide can be decreased when combined with Fluconazole. Approved, Investigational 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, Investigational Fluindione Leflunomide may increase the anticoagulant activities of Fluindione. Approved, 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 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 Flunixin The risk or severity of adverse effects can be increased when Leflunomide is combined with Flunixin. Vet Approved Flunoxaprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Flunoxaprofen. Experimental 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, Investigational Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Leflunomide. Approved Fluprednidene The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluprednidene. Approved, Withdrawn Fluprednisolone The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluprednisolone. Approved Fluprostenol The therapeutic efficacy of Fluprostenol can be decreased when used in combination with Leflunomide. Vet Approved Flurandrenolide The risk or severity of adverse effects can be increased when Leflunomide is combined with Flurandrenolide. Approved Flurbiprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Flurbiprofen. Approved, Investigational Fluticasone The risk or severity of adverse effects can be increased when Leflunomide is combined with Fluticasone. Approved, Experimental, 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 risk or severity of myopathy and rhabdomyolysis can be increased when Leflunomide is combined with Fluvastatin. Approved 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 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 Fosphenytoin The metabolism of Leflunomide can be increased when combined with Fosphenytoin. Approved, Investigational Framycetin Leflunomide may decrease the excretion rate of Framycetin which could result in a higher serum level. 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 Garenoxacin Leflunomide may increase the neuroexcitatory activities of Garenoxacin. 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 Leflunomide is combined with Gemcitabine. 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 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 GI-5005 The risk or severity of adverse effects can be increased when Leflunomide is combined with GI-5005. Investigational Ginseng The risk or severity of adverse effects can be increased when Leflunomide is combined with Ginseng. Approved, Investigational, Nutraceutical Gitoformate Gitoformate may decrease the cardiotoxic activities of Leflunomide. Experimental Glatiramer 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 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. Approved, Investigational, Withdrawn GS 0573 The risk or severity of adverse effects can be increased when GS 0573 is combined with Leflunomide. Investigational Guacetisal The risk or severity of adverse effects can be increased when Leflunomide is combined with Guacetisal. Experimental Gusperimus The risk or severity of adverse effects can be increased when Gusperimus is combined with Leflunomide. Investigational Halcinonide The risk or severity of adverse effects can be increased when Leflunomide is combined with Halcinonide. Approved, Investigational, Withdrawn 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 Hepatitis A Vaccine The risk or severity of adverse effects can be increased when Leflunomide is combined with Hepatitis A Vaccine. Approved Hepatitis B Vaccine (Recombinant) The risk or severity of adverse effects can be increased when Leflunomide is combined with Hepatitis B Vaccine (Recombinant). Approved, Withdrawn 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 Human C1-esterase inhibitor The risk or severity of adverse effects can be increased when Human C1-esterase inhibitor is combined with Leflunomide. Approved Human rabies virus immune globulin The risk or severity of adverse effects can be increased when Leflunomide is combined with Human rabies virus immune globulin. Approved Hydralazine Leflunomide may decrease the antihypertensive activities of Hydralazine. Approved Hydrocortisone The risk or severity of adverse effects can be increased when Leflunomide is combined with Hydrocortisone. Approved, Vet Approved Hydrocortisone acetate The risk or severity of adverse effects can be increased when Leflunomide is combined with Hydrocortisone acetate. Approved, Vet Approved Hydrocortisone butyrate The risk or severity of adverse effects can be increased when Leflunomide is combined with Hydrocortisone butyrate. Approved, Vet Approved Hydroflumethiazide The therapeutic efficacy of Hydroflumethiazide can be decreased when used in combination with Leflunomide. Approved, Investigational 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 Hygromycin B Leflunomide may decrease the excretion rate of Hygromycin B which could result in a higher serum level. Vet Approved Hypericin The risk or severity of adverse effects can be increased when Hypericin is combined with Leflunomide. Investigational Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Leflunomide. Approved, Investigational Ibrutinib The risk or severity of adverse effects can be increased when Ibrutinib is 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, Investigational Icosapent The risk or severity of adverse effects can be increased when Leflunomide is combined with Icosapent. Approved, Nutraceutical 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 Idraparinux Leflunomide may increase the anticoagulant activities of Idraparinux. Investigational 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 Leflunomide is combined with Imidapril. Investigational Imidazole salicylate The risk or severity of adverse effects can be increased when Leflunomide is combined with Imidazole salicylate. Experimental 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 Indisulam The metabolism of Indisulam can be decreased when combined with Leflunomide. Investigational Indobufen The risk or severity of adverse effects can be increased when Leflunomide is combined with Indobufen. Investigational Indomethacin The risk or severity of adverse effects can be increased when Leflunomide is combined with Indomethacin. 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 Leflunomide is combined with Irinotecan. Approved, Investigational Isavuconazole The serum concentration of Leflunomide can be increased when it is combined with Isavuconazole. Approved, Investigational Isepamicin Leflunomide may decrease the excretion rate of Isepamicin which could result in a higher serum level. Experimental Isoxicam The risk or severity of adverse effects can be increased when Leflunomide is combined with Isoxicam. Withdrawn Istaroxime The risk or severity of adverse effects can be increased when Leflunomide is combined with Istaroxime. Investigational Ixazomib The metabolism of Ixazomib can be decreased when combined with Leflunomide. Approved, Investigational Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Leflunomide is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated). Approved Kanamycin Leflunomide may decrease the excretion rate of Kanamycin which could result in a higher serum level. Approved, Investigational, 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, Investigational Ketoconazole The metabolism of Leflunomide can be decreased when combined with Ketoconazole. Approved, Investigational Ketoprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Ketoprofen. Approved, Vet Approved L-Phenylalanine The risk or severity of adverse effects can be increased when L-Phenylalanine is combined with Leflunomide. Approved, Investigational, Nutraceutical Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Leflunomide. Experimental Landiolol Leflunomide may decrease the antihypertensive activities of Landiolol. Investigational Lansoprazole The metabolism of Lansoprazole can be decreased when combined with Leflunomide. Approved, Investigational Latanoprostene Bunod The therapeutic efficacy of Latanoprostene Bunod 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, Investigational Letaxaban Leflunomide may increase the anticoagulant activities of Letaxaban. Investigational Levobetaxolol Leflunomide may decrease the antihypertensive activities of Levobetaxolol. Approved, Investigational 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 Limaprost The therapeutic efficacy of Limaprost can be decreased when used in combination with Leflunomide. Approved, Investigational Lisinopril The risk or severity of adverse effects can be increased when Leflunomide is combined with Lisinopril. Approved, Investigational Lisofylline The risk or severity of adverse effects can be increased when Lisofylline is combined with Leflunomide. Investigational Lithium cation The serum concentration of Lithium can be increased when it is combined with Leflunomide. Experimental Lobeglitazone The metabolism of Leflunomide can be decreased when combined with Lobeglitazone. Approved, Investigational Lomefloxacin Leflunomide may increase the neuroexcitatory activities of Lomefloxacin. Approved, Investigational Lomustine The risk or severity of adverse effects can be increased when Lomustine is combined with Leflunomide. Approved, Investigational Lonazolac The risk or severity of adverse effects can be increased when Leflunomide is combined with Lonazolac. Experimental Lornoxicam The risk or severity of adverse effects can be increased when Leflunomide is combined with Lornoxicam. Approved, Investigational Loteprednol The risk or severity of adverse effects can be increased when Leflunomide is combined with Loteprednol. 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, Investigational 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 Luprostiol The therapeutic efficacy of Luprostiol can be decreased when used in combination with Leflunomide. Vet Approved 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, Investigational 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, Investigational Meclofenamic acid The risk or severity of adverse effects can be increased when Leflunomide is combined with Meclofenamic acid. Approved, Vet Approved Medical Cannabis The metabolism of Medical Cannabis can be decreased when combined with Leflunomide. Experimental, Investigational Medrysone The risk or severity of adverse effects can be increased when Leflunomide is combined with Medrysone. Approved Mefenamic acid The risk or severity of adverse effects can be increased when Leflunomide is combined with Mefenamic acid. Approved Melagatran Leflunomide may increase the anticoagulant activities of Melagatran. Experimental Melatonin The metabolism of Melatonin can be decreased when combined with Leflunomide. Approved, Nutraceutical, Vet Approved Melengestrol The risk or severity of adverse effects can be increased when Leflunomide is combined with Melengestrol. Vet Approved Meloxicam The risk or severity of adverse effects can be increased when Leflunomide is combined with Meloxicam. 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 Mepindolol Leflunomide may decrease the antihypertensive activities of Mepindolol. Experimental 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 The risk or severity of adverse effects can be increased when Leflunomide is combined with 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. Approved, Investigational, Withdrawn Methadone The metabolism of Methadone can be decreased when combined with Leflunomide. Approved Methimazole The risk or severity of adverse effects can be increased when Leflunomide is combined with Methimazole. 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, Investigational, 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 Leflunomide is combined with Methylprednisolone. Approved, Vet Approved Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Leflunomide. Experimental 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 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, Investigational Micronomicin Leflunomide may decrease the excretion rate of Micronomicin which could result in a higher serum level. Experimental Midostaurin The metabolism of Leflunomide can be decreased when combined with Midostaurin. Approved, Investigational Mifamurtide The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Leflunomide. Approved, Experimental 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, Investigational Moexipril The risk or severity of adverse effects can be increased when Leflunomide is combined with Moexipril. Approved Mofebutazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Mofebutazone. Experimental 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 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 Nabilone The metabolism of Leflunomide can be decreased when combined with Nabilone. Approved, Investigational Nabiximols The metabolism of Nabiximols can be decreased when combined with Leflunomide. Approved, Investigational 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, Investigational 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, Investigational 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 Neamine Leflunomide may decrease the excretion rate of Neamine which could result in a higher serum level. Experimental Nebivolol Leflunomide may decrease the antihypertensive activities of Nebivolol. Approved, Investigational Nelarabine The risk or severity of adverse effects can be increased when Nelarabine is combined with Leflunomide. Approved, Investigational Nemonoxacin Leflunomide may increase the neuroexcitatory activities of Nemonoxacin. Investigational Nepafenac The risk or severity of adverse effects can be increased when Leflunomide is combined with Nepafenac. Approved, Investigational Netilmicin Leflunomide may decrease the excretion rate of Netilmicin which could result in a higher serum level. Approved, Investigational Netupitant The metabolism of Netupitant can be decreased when combined with Leflunomide. Approved, Investigational Nevirapine The metabolism of Leflunomide can be decreased when combined with Nevirapine. Approved Niclosamide The metabolism of Niclosamide can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Nifenazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Nifenazone. Experimental 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 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, Investigational Ocrelizumab Ocrelizumab may increase the immunosuppressive activities of Leflunomide. Approved, Investigational Ofloxacin Leflunomide may increase the neuroexcitatory activities of Ofloxacin. Approved Oleandrin Oleandrin may decrease the cardiotoxic activities of Leflunomide. Experimental, Investigational 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 bleeding can be increased when Leflunomide is combined with Omacetaxine mepesuccinate. Approved, Investigational Omapatrilat The risk or severity of adverse effects can be increased when Leflunomide is combined with Omapatrilat. Investigational Orgotein The risk or severity of adverse effects can be increased when Leflunomide is combined with Orgotein. Vet 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, Investigational Otamixaban Leflunomide may increase the anticoagulant activities of Otamixaban. Investigational 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 risk or severity of adverse effects can be increased when Leflunomide is combined with Oxaprozin. Approved Oxolinic acid Leflunomide may increase the neuroexcitatory activities of Oxolinic acid. Experimental 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. Approved, 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, Investigational Palmidrol The risk or severity of adverse effects can be increased when Leflunomide is combined with Palmidrol. Experimental, Nutraceutical 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 Paquinimod The risk or severity of adverse effects can be increased when Paquinimod is combined with Leflunomide. 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 Parthenolide The risk or severity of adverse effects can be increased when Leflunomide is combined with Parthenolide. 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 Pentaerythritol Tetranitrate Leflunomide may increase the anticoagulant activities of Pentaerythritol Tetranitrate. Approved 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 Leflunomide is combined with Perindopril. Approved Perphenazine The metabolism of Perphenazine can be decreased when combined with Leflunomide. Approved Peruvoside Peruvoside may decrease the cardiotoxic activities of Leflunomide. Experimental Phenacetin The metabolism of Phenacetin can be decreased when combined with Leflunomide. Withdrawn Phenindione Leflunomide may increase the anticoagulant activities of Phenindione. Approved, Investigational Phenprocoumon Leflunomide may increase the anticoagulant activities of Phenprocoumon. Approved, Investigational Phenylbutazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Phenylbutazone. 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, Investigational Pioglitazone The metabolism of Pioglitazone can be decreased when combined with Leflunomide. Approved, Investigational Pipemidic acid Leflunomide may increase the neuroexcitatory activities of Pipemidic acid. Experimental Piperaquine The metabolism of Piperaquine 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 The therapeutic efficacy of Piretanide can be decreased when used in combination with Leflunomide. Approved Pirfenidone The risk or severity of adverse effects can be increased when Pirfenidone is combined with Leflunomide. Approved, Investigational Piromidic acid Leflunomide may increase the neuroexcitatory activities of Piromidic acid. Experimental Piroxicam The risk or severity of adverse effects can be increased when Leflunomide is combined with Piroxicam. Approved, Investigational Pirprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Pirprofen. Experimental Pitavastatin The metabolism of Pitavastatin can be decreased when combined with Leflunomide. Approved Pitolisant The risk or severity of adverse effects can be increased when Leflunomide is combined with Pitolisant. Approved, Investigational Platelet Activating Factor Leflunomide may decrease the antihypertensive activities of Platelet Activating Factor. Experimental Plazomicin Leflunomide may decrease the excretion rate of Plazomicin which could result in a higher serum level. Approved, Investigational 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 Potassium Citrate Leflunomide may increase the anticoagulant activities of Potassium Citrate. Approved, Investigational, Vet 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, Investigational Pranoprofen The risk or severity of adverse effects can be increased when Leflunomide is combined with Pranoprofen. Experimental, Investigational Prasterone The risk or severity of adverse effects can be increased when Leflunomide is combined with Prasterone. Approved, Investigational, Nutraceutical Prasterone sulfate The risk or severity of adverse effects can be increased when Leflunomide is combined with Prasterone 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, Investigational Prednisolone The risk or severity of adverse effects can be increased when Leflunomide is combined with Prednisolone. 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. Approved, Experimental, Investigational 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, Investigational Procarbazine The risk or severity of adverse effects can be increased when Procarbazine is combined with Leflunomide. Approved, Investigational Progesterone The metabolism of Progesterone can be decreased when combined with Leflunomide. Approved, Vet Approved Proglumetacin The risk or severity of adverse effects can be increased when Leflunomide is combined with Proglumetacin. Experimental 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, Investigational Propofol The metabolism of Propofol can be decreased when combined with Leflunomide. Approved, Investigational, Vet Approved Propyphenazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Propyphenazone. Experimental Proquazone The risk or severity of adverse effects can be increased when Leflunomide is combined with Proquazone. Experimental Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Leflunomide. Experimental 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 Prostalene The therapeutic efficacy of Prostalene can be decreased when used in combination with Leflunomide. Vet Approved Protein C Leflunomide may increase the anticoagulant activities of Protein C. Approved Protein S human Leflunomide may increase the anticoagulant activities of Protein S human. Approved Protocatechualdehyde Leflunomide may increase the anticoagulant activities of Protocatechualdehyde. 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, Investigational, 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 Leflunomide is combined with Quinapril. 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, Investigational Quinine The metabolism of Leflunomide can be decreased when combined with Quinine. Approved Rabies virus inactivated antigen, A The risk or severity of adverse effects can be increased when Leflunomide is combined with Rabies virus inactivated antigen, A. Approved, Investigational Rabies virus inactivated antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Leflunomide. Approved, Investigational Ramipril The risk or severity of adverse effects can be increased when Leflunomide is combined with Ramipril. Approved Rescinnamine The risk or severity of adverse effects can be increased when Leflunomide is combined with Rescinnamine. Approved Resveratrol The risk or severity of adverse effects can be increased when Leflunomide is combined with Resveratrol. Approved, Experimental, Investigational Reviparin Leflunomide may increase the anticoagulant activities of Reviparin. Approved, Investigational Ribostamycin Leflunomide may decrease the excretion rate of Ribostamycin which could result in a higher serum level. Approved, Investigational 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, Investigational Rilonacept The risk or severity of adverse effects can be increased when Rilonacept is combined with Leflunomide. Approved, Investigational 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 Rindopepimut. 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. Approved, 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, Investigational Rosoxacin Leflunomide may increase the neuroexcitatory activities of Rosoxacin. Approved, Investigational Rosuvastatin The risk or severity of myopathy and rhabdomyolysis can be increased when Leflunomide is combined with Rosuvastatin. Approved Rotavirus Vaccine The risk or severity of adverse effects can be increased when Leflunomide is combined with Rotavirus Vaccine. Approved Rubella virus vaccine The risk or severity of adverse effects can be increased when Leflunomide is combined with Rubella virus vaccine. Approved, Investigational Rucaparib The metabolism of Leflunomide can be decreased when combined with Rucaparib. Approved, Investigational Rufloxacin Leflunomide may increase the neuroexcitatory activities of Rufloxacin. Experimental Rupatadine The metabolism of Rupatadine 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 Salmonella typhi ty2 vi polysaccharide antigen The risk or severity of adverse effects can be increased when Leflunomide is combined with Salmonella typhi ty2 vi polysaccharide antigen. Approved Salmonella typhi Ty21a live antigen The risk or severity of adverse effects can be increased when Leflunomide is combined with Salmonella typhi ty21a live antigen. 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 Saralasin The risk or severity of adverse effects can be increased when Saralasin is combined with Leflunomide. Investigational Sarilumab Sarilumab may increase the immunosuppressive activities of Leflunomide. Approved, Investigational 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 Seliciclib The risk or severity of adverse effects can be increased when Leflunomide is combined with Seliciclib. Investigational Semapimod The risk or severity of adverse effects can be increased when Semapimod is combined with Leflunomide. Investigational Seocalcitol The risk or severity of adverse effects can be increased when Seocalcitol is combined with Leflunomide. Experimental, Investigational Seratrodast The metabolism of Seratrodast can be decreased when combined with Leflunomide. Approved Serrapeptase The risk or severity of adverse effects can be increased when Leflunomide is combined with Serrapeptase. Investigational 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, Investigational 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, Investigational 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 Sitafloxacin Leflunomide may increase the neuroexcitatory activities of Sitafloxacin. Experimental, 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 Sparfloxacin Leflunomide may increase the neuroexcitatory activities of Sparfloxacin. Approved, Investigational Spirapril The risk or severity of adverse effects can be increased when Leflunomide is combined with Spirapril. 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, Investigational Sulfadiazine The metabolism of Leflunomide can be decreased when combined with Sulfadiazine. Approved, Investigational, 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 The risk or severity of adverse effects can be increased when Leflunomide is combined with 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 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 risk or severity of adverse effects can be increased when Leflunomide is combined with Suprofen. Approved, Withdrawn Suxibuzone The risk or severity of adverse effects can be increased when Leflunomide is combined with Suxibuzone. Experimental Tacrolimus Tacrolimus may increase the immunosuppressive activities of Leflunomide. Approved, Investigational Tafluprost The therapeutic efficacy of Tafluprost can be decreased when used in combination with Leflunomide. Approved Talinolol Leflunomide may decrease the antihypertensive activities of Talinolol. Investigational 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 Tarenflurbil The risk or severity of adverse effects can be increased when Leflunomide is combined with Tarenflurbil. Investigational Tasosartan The risk or severity of adverse effects can be increased when Tasosartan is combined with Leflunomide. Approved Tecemotide The risk or severity of adverse effects can be increased when Leflunomide is combined with Tecemotide. Investigational Technetium Tc-99m etidronate The risk or severity of adverse effects can be increased when Leflunomide is combined with Technetium Tc-99m etidronate. 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, Investigational Temocapril The risk or severity of adverse effects can be increased when Leflunomide is combined with Temocapril. 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 Tenidap The risk or severity of adverse effects can be increased when Leflunomide is combined with Tenidap. Experimental 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 disoproxil. Approved, Investigational Tenoxicam The risk or severity of adverse effects can be increased when Leflunomide is combined with Tenoxicam. Approved Tepoxalin The risk or severity of adverse effects can be increased when Tepoxalin is combined with Leflunomide. Vet Approved Terbutaline Leflunomide may decrease the antihypertensive activities of Terbutaline. Approved Terfenadine The metabolism of Terfenadine can be decreased when combined with Leflunomide. Approved, Withdrawn Teriflunomide The risk or severity of adverse effects can be increased when Leflunomide is combined with Teriflunomide. Approved Tertatolol Leflunomide may decrease the antihypertensive activities of Tertatolol. Experimental Testosterone The metabolism of Testosterone can be decreased when combined with Leflunomide. Approved, Investigational Testosterone cypionate The metabolism of Testosterone cypionate can be decreased when combined with Leflunomide. Approved Testosterone enanthate The metabolism of Testosterone enanthate can be decreased when combined with Leflunomide. Approved Testosterone undecanoate The metabolism of Testosterone undecanoate can be decreased when combined with Leflunomide. Approved, Investigational Tetrandrine The risk or severity of adverse effects can be increased when Leflunomide is combined with Tetrandrine. Experimental TG4010 The risk or severity of adverse effects can be increased when Leflunomide is combined with TG4010. 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, Investigational 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 Tiludronic acid. Approved, Investigational, 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 Tioclomarol Leflunomide may increase the anticoagulant activities of Tioclomarol. Experimental 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, Withdrawn 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, Investigational Tolmetin The risk or severity of adverse effects can be increased when Leflunomide is combined with Tolmetin. Approved Tolterodine The metabolism of Tolterodine can be decreased when combined with Leflunomide. Approved, Investigational Topiroxostat The metabolism of Leflunomide can be decreased when combined with Topiroxostat. Approved, Investigational Topotecan The risk or severity of adverse effects can be increased when Topotecan is combined with Leflunomide. Approved, Investigational Torasemide The therapeutic efficacy of Torasemide can be decreased when used in combination with Leflunomide. Approved Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Leflunomide. Approved, Investigational 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 Leflunomide is combined with Trandolapril. Approved 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, Investigational 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 Tribenoside The risk or severity of adverse effects can be increased when Leflunomide is combined with Tribenoside. Experimental Trichlormethiazide The therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Leflunomide. Approved, Vet 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 Triptolide The risk or severity of adverse effects can be increased when Triptolide is combined with Leflunomide. Investigational 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. Investigational, Withdrawn Trovafloxacin Leflunomide may increase the neuroexcitatory activities of Trovafloxacin. Approved, Investigational, Withdrawn Troxerutin Leflunomide may increase the anticoagulant activities of Troxerutin. Investigational Ulobetasol The risk or severity of adverse effects can be increased when Leflunomide is combined with Ulobetasol. Approved Unoprostone The therapeutic efficacy of Unoprostone can be decreased when used in combination with Leflunomide. Approved, Investigational 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. Approved, Investigational, Withdrawn Valsartan The metabolism of Leflunomide can be decreased when combined with Valsartan. Approved, Investigational Varicella Zoster Vaccine (Live/Attenuated) The risk or severity of adverse effects can be increased when Leflunomide is combined with Varicella Zoster Vaccine (Live/Attenuated). 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 Vicriviroc The metabolism of Vicriviroc can be decreased when combined with Leflunomide. Investigational 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, Investigational 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, Investigational Voclosporin The risk or severity of adverse effects can be increased when Voclosporin 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, Investigational Warfarin Leflunomide may increase the anticoagulant activities of Warfarin. Approved Wortmannin The risk or severity of adverse effects can be increased when Wortmannin is combined with Leflunomide. Experimental Ximelagatran The metabolism of Ximelagatran can be decreased when combined with Leflunomide. Approved, Investigational, Withdrawn Yellow Fever Vaccine The risk or severity of adverse effects can be increased when Leflunomide is combined with Yellow Fever Vaccine. Approved, Investigational 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, Investigational Zaltoprofen The metabolism of Zaltoprofen can be decreased when combined with Leflunomide. Approved, Investigational Zidovudine The risk or severity of adverse effects can be increased when Leflunomide is combined with Zidovudine. Approved Zileuton The metabolism of Zileuton can be decreased when combined with Leflunomide. Approved, Investigational, Withdrawn Zofenopril The risk or severity of adverse effects can be increased when Leflunomide is combined with Zofenopril. Experimental 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 Zucapsaicin The metabolism of Leflunomide can be decreased when combined with Zucapsaicin. Approved, Investigational - 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
- Human Metabolome Database
- HMDB0015229
- 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
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Leflunomide
- ATC Codes
- L04AA13 — Leflunomide
- AHFS Codes
- 92:36.00 — Disease-modifying Antirheumatic Agents
- FDA label
- Download (1.23 MB)
- MSDS
- Download (105 KB)
Clinical Trials
- Clinical Trials
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 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 100 mg Tablet, film coated Oral 20 mg 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 10 mg/1 Tablet, film coated 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-00di-0390000000-1ac4065d1ef245442a16 MS/MS Spectrum - , positive LC-MS/MS splash10-03di-2920000000-819d0674f452a60be1a4
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 show 3 more
- Substituents
- Aromatic anilide / Trifluoromethylbenzene / Azole / Isoxazole / Heteroaromatic compound / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid derivative / Organoheterocyclic compound / Azacycle show 13 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- monocarboxylic acid amide, isoxazoles, (trifluoromethyl)benzenes (CHEBI:6402)
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ubiquinone binding
- Specific Function
- Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
- Gene Name
- DHODH
- Uniprot ID
- Q02127
- 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]
- 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...
- 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]
- 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 regulat...
- 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
- 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 un...
- 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]
- 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 un...
- 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
- 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 fro...
- 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 August 15, 2018 09:48