Last reviewed 2026-04-20 · How we verify

Arava (LEFLUNOMIDE)

Arava works by inhibiting the enzyme Cytochrome P450 1A2, which is involved in the production of inflammatory chemicals in the body.

Arava (Leflunomide) is a small molecule antirheumatic agent developed by Sanofi Aventis US, targeting Cytochrome P450 1A2. It is used to treat psoriasis with arthropathy and rheumatoid arthritis, and has been FDA-approved since 1998. Arava is now off-patent, with 12 generic manufacturers available. As an off-patent medication, its commercial status is generic. Key safety considerations include monitoring for liver function and potential interactions with other medications.

At a glance

Mechanism of action

Mechanism of Action. Leflunomide is an isoxazole immunomodulatory agent which inhibits dihydroorotate dehydrogenase (an enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity. Several in vivo and in vitro experimental models have demonstrated an anti-inflammatory effect.

Approved indications

• Psoriasis with arthropathy
• Rheumatoid arthritis

Boxed warnings

• 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 prior to initiating leflunomide tablets therapy. ( 5.1 , 8.3 ) Advise use of effective contraception in females of reproductive potential during treatment and during a drug elimination procedure. ( 5.1 , 5.3 , 8.3 ) Stop leflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant. ( 5.1 , 5.3 , 8.1 ) Hepatotoxicity Severe liver injury and fatal liver failure have been reported. ( 5.2 ) Avoid leflunomide use in patients with pre-existing liver disease, or those with serum alanine aminotransferase (ALT)>2xULN. ( 5.2 , 8.6 ) Use caution when leflunomide is given with other potentially hepatotoxic drugs. ( 5.2 ) Monitor ALT levels. Interrupt leflunomide treatment if ALT elevation > 3 fold ULN. If likely leflunomide-induced, start accelerated drug elimination procedure and monitor liver tests weekly until normalized. ( 5.2 , 5.3 )

Common side effects

• Respiratory Infection
• Diarrhea
• GI/Abdominal Pain
• Nausea
• Vomiting
• Alopecia
• Dyspepsia
• Bronchitis
• Injury Accident
• Headache
• Dizziness
• Back Pain

Drug interactions

• warfarin

Key clinical trials

• Treatment Strategies for IgG4-RD Patients With Superficial Organ Involvement (NA)
• Venlafaxine as Adjunct Therapy in Rheumatoid Arthritis (PHASE2)
• Leflunomide in Previously Treated Metastatic Triple Negative Cancers (PHASE1,PHASE2)
• A Study of the Effectiveness of Additional Risk Minimization Measures Related to ARAVA® (Leflunomide) in Saudi Arabia
• Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (PHASE2)
• Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients (PHASE4)
• "Effect of Vitamin E (α-Tocopherol) on Clinical Activity and Inflammation in Rheumatoid Arthritis" (PHASE2,PHASE3)
• Analysis of T and B Cell Repertoire Changes in Response to Orencia® (Abatacept) in Rheumatoid Arthritis

Primary sources

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