November 27, 2015
Recommended Topic Related To:


"Rheumatoid arthritis overview

Rheumatoid arthritis (RA) is a disease in which the body's immune system attacks its own joints. This results in pain, swelling and potentially permanent damage. About 1.5 million people in the United State"...


Arava Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 7/10/2015

Arava (leflunomide) is a pyrimidine synthesis inhibitor belonging to the disease-modifying anti-rheumatic class of drugs (DMARD) used to treat symptoms of rheumatoid arthritis. Arava also helps reduce joint damage and improves physical functioning. Arava is available in generic form. Common side effects of Arava include diarrhea, nausea, stomach pain, loss of appetite, weight loss, headache, dizziness, back pain, numbness or tingling, runny or stuffy nose, cold symptoms, or itching or skin rash. In rare cases, Arava may cause serious or fatal liver disease.

Arava is available in doses of 10, 20, or 100 mg tablets. It is usually taken orally once/day or as directed. Arava may adversely interact with warfarin, rifamycins, drugs affecting the liver, cholestyramine, and other drugs that weaken the immune system. Discuss all medications you are taking with your doctor. Avoid being near people with contagious illnesses, as Arava can make it easier to get sick. If you already have liver disease Arava should not be used. Arava must not be used during pregnancy. It may cause birth defects. Before starting this medication, women of childbearing age must have a negative pregnancy test. Two effective forms of birth control (e.g., condoms and birth control pills) must be used while taking this medication. Arava may pass into breast milk and could have undesirable effects on a nursing infant. Breast-feeding is not recommended. After stopping Arava, you may need other medications to help your body eliminate the drug. Without a drug elimination procedure, Arava could stay in the body for up to 2 years.

Our Arava Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Arava in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using leflunomide and call your doctor at once if you have any of these serious side effects:

  • fever, chills, body aches, flu symptoms;
  • white patches or sores inside your mouth or on your lips;
  • chest pain;
  • chest pain, dry cough, wheezing, feeling short of breath (you may also have a fever);
  • pain or burning when you urinate;
  • pale skin, easy bruising or bleeding, unusual weakness;
  • nausea, stomach pain, loss of appetite, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • fever, sore throat, and headache with a severe blistering, peeling, and red skin rash.

Less serious side effects may include:

  • mild stomach pain, diarrhea, loss of appetite;
  • weight loss;
  • headache, dizziness;
  • back pain;
  • numbness or tingling;
  • runny or stuffy nose, cold symptoms; or
  • mild itching or skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Arava (Leflunomide)

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Arava Overview - Patient Information: Side Effects

SIDE EFFECTS: Diarrhea, nausea, and dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: cough, numbness/tingling of hands/feet, hair loss, chest pain, fast/pounding heartbeat, increased thirst/urination, muscle cramp/pain, mental/mood changes, vision changes, easy bruising/bleeding, unusual growths/lumps, swollen glands (lymph nodes), unexplained weight loss, unusual tiredness.

Leflunomide may increase blood pressure. Your blood pressure should be checked regularly while you are taking this medication.

This medication can lower the body's ability to fight an infection. Tell your doctor immediately if you develop any signs of an infection such as fever, chills, or persistent sore throat.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Leflunomide can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Therefore, seek immediate medical attention if you develop any rash.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Arava (Leflunomide)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Arava FDA Prescribing Information: Side Effects
(Adverse Reactions)


The following serious adverse reactions are described elsewhere in the labeling:

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

In clinical studies (Trials 1, 2, and 3), 1,865 patients were treated with ARAVA administered as either monotherapy or in combination with methotrexate or sulfasalazine. Patients ranged in age from 19 to 85 years, with an overall median age of 58 years. The mean duration of RA was 6 years ranging from 0 to 45 years.

Elevation of Liver Enzymes

Treatment with ARAVA was associated with elevations of liver enzymes, primarily ALT and AST, in a significant number of patients; these effects were generally reversible. Most transaminase elevations were mild ( ≤ 2-fold ULN) and usually resolved while continuing treatment. Marked elevations ( > 3-fold ULN) occurred infrequently and reversed with dose reduction or discontinuation of treatment. Table 1 shows liver enzyme elevations seen with monthly monitoring in clinical trials Trial 1 and Trial 2. It was notable that the absence of folate use in Trial 3 was associated with a considerably greater incidence of liver enzyme elevation on methotrexate.

Table 1: Liver Enzyme Elevations > 3-fold Upper Limits of Normal (ULN) in Patients with RA in Trials 1, 2, and 3**

  Trial 1 Trial 2 Trial 3*
ARAVA 20 mg/day
(n= 182)
MTX 7.5 - 15 mg/wk
ARAVA 20mg/day
SSZ 2.0 g/day
ARAVA 20 mg/day
MTX 7.5 - 15 mg/wk
ALT (SGPT) > 3-fold ULN (n %) 8 (4.4) 3 (2.5) 5 (2.7) 2 (1.5) 1 (1.1) 2 (1.5) 13 (2.6) 83 (16.7)
Reversed to ≤ 2-fold ULN: 8 3 5 2 1 2 12 82
Timing of Elevation
  0-3 Months 6 1 1 2 1 2 7 27
  4-6 Months 1 1 3 - - - 1 34
  7-9 Months 1 1 1 - - - - 16
  10-12 Months - - - - - - 5 6
MTX = methotrexate, PL = placebo, SSZ = sulfasalazine, ULN = Upper limit of normal
*Only 10% of patients in Trial 3 received folate. All patients in Trial 1 received folate.

In a 6 month study of 263 patients with persistent active rheumatoid arthritis despite methotrexate therapy, and with normal LFTs, ARAVA was administered to a group of 130 patients starting at 10 mg per day and increased to 20 mg as needed. An increase in ALT greater than or equal to three times the ULN was observed in 3.8% of patients compared to 0.8% in 133 patients continued on methotrexate with placebo.

Most Common Adverse Reactions

The most common adverse reactions in ARAVA-treated patients with RA include diarrhea, elevated liver enzymes (ALT and AST), alopecia and rash. Table 2 displays the most common adverse reactions in the controlled studies in patients with RA at one year ( ≥ 5% in any ARAVA treatment group).

Table 2: Percentage Of Patients With Adverse Events ≥ 5% In Any ARAVA Treated Group in all RA Studies in Patients with RA

  Placebo-Controlled Trials Active-Controlled Trials All RA Studies
Trial 1 and 2 Trial 3 1  
ARAVA 20 mg/day
SSZ 2.0g/day
MTX 7.5 - 15 mg/wk
ARAVA 20 mg/day
MTX 7.5 - 15 mg/wk
Diarrhea 27% 12% 10% 20% 22% 10% 17%
Headache 13% 11% 12% 21% 10% 8% 7%
Nausea 13% 11% 19% 18% 13% 18% 9%
Rash 12% 7% 11% 9% 11% 10% 10%
Abnormal Liver Enzymes 10% 2% 4% 10% 6% 17% 5%
Alopecia 9% 1% 6% 6% 17% 10% 10%
Hypertension3 9% 4% 4% 3% 10% 4% 10%
Asthenia 6% 4% 5% 6% 3% 3% 3%
Back Pain 6% 3% 4% 9% 8% 7% 5%
GI/Abdominal Pain 6% 4% 7% 8% 8% 8% 5%
Abdominal Pain 5% 4% 4% 8% 6% 4% 6%
Allergic Reaction 5% 2% 0% 6% 1% 2% 2%
Bronchitis 5% 2% 4% 7% 8% 7% 7%
Dizziness 5% 3% 6% 5% 7% 6% 4%
Mouth Ulcer 5% 4% 3% 10% 3% 6% 3%
Pruritus 5% 2% 3% 2% 6% 2% 4%
Rhinitis 5% 2% 4% 3% 2% 2% 2%
Vomiting 5% 4% 4% 3% 3% 3% 3%
Tenosynovitis 2% 0% 1% 2% 5% 1% 3%
MTX = methotrexate, PL = placebo, SSZ = sulfasalazine
1 Only 10% of patients in Trial3 received folate. All patients in Trial 1 received folate; none in Trial 2 received folate.
2 Includes all controlled and uncontrolled trials with ARAVA (duration up to 12 months).
3Hypertension as a preexisting condition was overrepresented in all ARAVA treatment groups in phase III trials

Adverse events during a second year of treatment with ARAVA in clinical trials were consistent with those observed during the first year of treatment and occurred at a similar or lower incidence.

Less Common Adverse Reactions

In addition, in controlled clinical trials, the following adverse events in the ARAVA treatment group occurred at a higher incidence than in the placebo group. These adverse events were deemed possibly related to the study drug.

Blood and Lymphatic System: leukocytosis, thrombocytopenia;

Cardiovascular: chest pain, palpitation, thrombophlebitis of the leg, varicose vein;

Eye: blurred vision, eye disorder, papilledema, retinal disorder, retinal hemorrhage;

Gastrointestinal: alkaline phosphatase increased, anorexia, bilirubinemia, flatulence, gamma-GT increased, salivary gland enlarged, sore throat, vomiting, dry mouth;

General Disorders: malaise;

Immune System: anaphylactic reaction;

Infection: abscess, flu syndrome, vaginal moniliasis;

Nervous System: dizziness, headache, somnolence;

Respiratory System: dyspnea;

Post Marketing Experience

The following additional adverse reactions have been identified during postapproval use of ARAVA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System: agranulocytosis, leukopenia, neutropenia, pancytopenia;

Infection: opportunistic infections, severe infections including sepsis;

Gastrointestinal: acute hepatic necrosis, hepatitis, jaundice/cholestasis, pancreatitis; severe liver injury such as hepatic failure

Immune System: angioedema;

Nervous system: peripheral neuropathy;

Respiratory: interstitial lung disease, including interstitial pneumonitis and pulmonary fibrosis, which may be fatal;

Skin and Appendages: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis including cutaneous necrotizing vasculitis, cutaneous lupus erythematosus, pustular psoriasis or worsening psoriasis.

Read the entire FDA prescribing information for Arava (Leflunomide)

Arava - User Reviews

Arava User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Arava sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration


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