LEFLUNOMIDE
LEFLUNOMIDE is indicated for the treatment of Active rheumatoid arthritis.
How LEFLUNOMIDE Works
Leflunomide acts as a pyrimidine synthesis inhibitor by inhibiting dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme essential for *de novo* pyrimidine synthesis. By blocking this pathway, the drug exerts antiproliferative effects, particularly on activated T-lymphocytes, which are highly dependent on *de novo* synthesis for expansion. This results in a reduction of the inflammatory response associated with rheumatoid arthritis.
Details
- Status
- Discontinued
- First Approved
- 2005-09-13
- Routes
- ORAL
- Dosage Forms
- TABLET
Companies
LEFLUNOMIDE Approval History
What LEFLUNOMIDE Treats
1 indicationsLEFLUNOMIDE is approved for 1 conditions since its original approval in 2005. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Active rheumatoid arthritis
LEFLUNOMIDE Boxed Warning
EMBRYO-FETAL TOXICITY and HEPATOTOXICITY Embryo-Fetal Toxicity Leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. Teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level. Exclude pregnancy before the start of treatment with leflunomide in females of reproductive potential. Advise females of reproductive potential to use effective contraception during leflunomide treatment and duri...
WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY Embryo-Fetal Toxicity Leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. Teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level. Exclude pregnancy before the start of treatment with leflunomide in females of reproductive potential. Advise females of reproductive potential to use effective contraception during leflunomide treatment and during an accelerated drug elimination procedure after leflunomide treatment. Stop leflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant. [see Contraindications (4) , Warnings and Precautions ( 5.1 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), and Clinical Pharmacology (12.3) ] Hepatotoxicity Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide. Leflunomide is contraindicated in patients with severe hepatic impairment. Concomitant use of leflunomide with other potentially hepatotoxic drugs may increase the risk of liver injury. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) >2xULN before initiating treatment, are at increased risk and should not be treated with leflunomide. Monitor ALT levels at least monthly for six months after starting leflunomide, and thereafter every 6 to 8 weeks. If leflunomide-induced liver injury is suspected, stop leflunomide treatment, start an accelerated drug elimination procedure, and monitor liver tests weekly until normalized. [see Contraindications (4) , Warnings and Precautions ( 5.2 , 5.3 ), Use in Special Populations (8.6) ] WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity Teratogenicity and embryo-lethality occurred in animals administered leflunomide. ( 5.1 , 8.1 ) Exclude pregnancy
LEFLUNOMIDE Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
What's emerging in LEFLUNOMIDE's indications
See all emerging drugs →Phase 3 candidates targeting molecules with no FDA-approved drug, in indications LEFLUNOMIDE treats. First-in-class if their pivotal trials read out positive.
Clinical Trial Registry
34 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT04508790 | 19418 NCI-2020-01962, 19418 | Ph 2 | recruiting | Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma |
| NCT05014646 | 21049 NCI-2021-07263, 21049 | Ph 2 | active not recruiting | Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients |
| NCT06454383 | 23540 NCI-2024-04359, 23540 | Ph 1 | recruiting | Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer |
| NCT03709446 | GCO 18-1832 | Ph 1, Ph 2 | completed | Leflunomide in Previously Treated Metastatic Triple Negative Cancers |
| NCT03739853 SPEED results posted | 18/SC/0107 | Ph 4 | completed | Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial |
| NCT07138898 | 25-00380 | Ph 2 | not yet recruiting | Immunosuppressant Management in Rheumatology Patients Undergoing Elective Total Shoulder Arthroplasty |
| NCT05443425 | 22026 NCI-2022-05061, 22026 | Ph 1 | recruiting | Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies |
| NCT04212416 | 19202 NCI-2019-04532, 19202 | Ph 1 | active not recruiting | Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease |
| NCT04997993 | GCO 20-2528 | Ph 1 | recruiting | Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer |
| NCT02451748 results posted | 2015-0117 | Ph 4 | completed | IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA |
| NCT04532372 results posted | 20291 NCI-2020-05746, 20291 | Ph 1, Ph 2 | completed | Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy |
| NCT04361214 | IRB20-0622 | Ph 1 | terminated | Leflunomide in Mild COVID-19 Patients |
| NCT06229340 NТО-RAS | LS01 | Ph 2 | recruiting | Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations |
| NCT04463615 results posted | 19606 NCI-2020-02973, 19606 | Ph 2 | completed | Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders |
| NCT02509052 results posted | 15140 NCI-2015-01181, 15140 | Ph 1, Ph 2 | completed | Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma |
| NCT05937191 Lef for IPH | 2021-KY-001 | Ph 1, Ph 2 | recruiting | Leflunomide for Idiopathic Pulmonary Hemosiderosis in Children |
| NCT05007678 DEFEAT-COVID | 2020ZC01 | Ph 3 | completed | Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease |
| NCT05626348 | Response of DMARDs in RA QiluH | Ph 4 | recruiting | The Clinical Efficacy of Immunomodulators in RA Patients |
| NCT03449758 SariPRO results posted | SARILL08755 U1111-1197-7699, 2017-002951-27 | Ph 4 | completed | Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis |
| NCT01727193 | ZS-LEF | Ph 3 | completed | The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy |
| NCT02930343 results posted | JIP/IEC/2016/27/893 | Ph 3 | terminated | Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy |
| NCT03797872 POISE results posted | 18/SC/0261 | Ph 4 | completed | Psoriatic Oligoarthritis Intervention With Symptomatic thErapy |
| NCT03952832 | 18458 NCI-2019-00247, 18458 | Ph 2 | withdrawn | Leflunomide in Treating Patients With High-Risk Smoldering Multiple Myeloma |
| NCT02644499 | JIP/IEC/SC/2013/5/433 | Ph 4 | completed | Comparison of Combination Disease Modifying Antirheumatic Drugs With Methotrexate Therapy in Early Rheumatoid Arthritis |
| NCT02703194 | ChinaPLAGH-IgG4 | Ph 4 | completed | Leflunomide for Maintenance of Remission in IgG4 Related Disease |
| NCT01172639 results posted | CareRA 2008-007225-39 | Ph 4 | completed | Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis. |
| NCT01941095 results posted | ML28695 2013-000359-42 | Ph 3 | completed | A Study of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Rheumatoid Arthritis |
| NCT02373202 results posted | LTS13618 U1111-1160-6525 | Ph 3 | completed | A Study Assessing the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis (SARIL-RA-HARUKA) |
| NCT01709578 results posted | EFC10832 U1111-1115-8466, 2011-003538-16 | Ph 3 | completed | To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET) |
| NCT01768572 results posted | SFY13370 2012-003536-23, U1111-1133-7839 | Ph 3 | completed | To Evaluate The Safety of SAR153191 (REGN88) and Tocilizumab Added to Other RA Drugs in Patients With RA Who Are Not Responding to or Intolerant of Anti-TNF Therapy (SARIL-RA-ASCERTAIN) |
| NCT02057250 SARIL-RA-EASY results posted | MSC12665 2012-004339-21, U1111-1130-9931 | Ph 3 | completed | To Evaluate Sarilumab - SAR153191 (REGN88) - Auto-injector Device In Patients With Rheumatoid Arthritis |
| NCT01611675 | 12-088 | Ph 1 | terminated | Leflunomide+Vemurafenib in V600 Mutant Met. Melanoma |
| NCT01225393 | ALT4864g GA00932 | Ph 2 | completed | A Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patients With Active Rheumatoid Arthritis |
| NCT01659242 | YK 01-2012 | Ph 4 | terminated | Leflunomide Versus Sulfasalazine/Methotrexate in Rheumatoid Arthritis:an Ultrasound/Magnetic Resonance Imaging Study |
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
LEFLUNOMIDE FDA Label Details
Indications & Usage
LEFLUNOMIDE is indicated for the treatment of Active rheumatoid arthritis.
WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY Embryo-Fetal Toxicity Leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. Teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level. Exc...
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Full clinical data, patents, trials, and competitive landscape for leflunomide.
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.