August 30, 2015
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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)


Adverse reactions associated with the use of leflunomide in RA include diarrhea, elevated liver enzymes (ALT and AST), alopecia and rash. In the controlled studies at one year, the following adverse events were reported, regardless of causality. (See Table 9.)

Table 9: Percentage Of Patients With Adverse Events ≥ 3% In Any Leflunomide Treated Group

  All RA Studies Placebo-Controlled Trials Active-Controlled Trials
MN 301 and US 301 MN 302*
LEF (N=1339)1 LEF (N=315) PBO (N=210) SSZ (N=133) MTX (N=182) LEF (N=501) MTX (N=498)
Allergic Reaction 2% 5% 2% 0% 6% 1% 2%
Asthenia 3% 6% 4% 5% 6% 3% 3%
Flu Syndrome 2% 4% 2% 0% 7% 0% 0%
Infection, upper respiratory 4% 0% 0% 0% 0% 0% 0%
Injury Accident 5% 7% 5% 3% 11% 6% 7%
Pain Abdominal 2% 4% 2% 2% 5% 1% < 1%
Pain Back 6% 5% 4% 4% 8% 6% 4%
Pain 5% 6% 3% 4% 9% 8% 7%
Hypertension2 10% 9% 4% 4% 3% 10% 4%
- New onset of hypertension 1% < 1% 0% 2% 2% < 1%
Chest Pain 2% 4% 2% 2% 4% 1% 2%
Anorexia 3% 3% 2% 5% 2% 3% 3%
Diarrhea 17% 27% 12% 10% 20% 22% 10%
Dyspepsia 5% 10% 10% 9% 13% 6% 7%
Gastroenteritis 3% 1% 1% 0% 6% 3% 3%
Abnormal Liver Enzymes 5% 10% 2% 4% 10% 6% 17%
Nausea 9% 13% 11% 19% 18% 13% 18%
GI/Abdominal Pain 5% 6% 4% 7% 8% 8% 8%
Mouth Ulcer 3% 5% 4% 3% 10% 3% 6%
Vomiting 3% 5% 4% 4% 3% 3% 3%
Hypokalemia 1% 3% 1% 1% 1% 1% < 1%
Weight Loss3 4% 2% 1% 2% 0% 2% 2%
Arthralgia 1% 4% 3% 0% 9% < 1% 1%
Leg Cramps 1% 4% 2% 2% 6% 0% 0%
Joint Disorder 4% 2% 2% 2% 2% 8% 6%
Synovitis 2% < 1% 1% 0% 2% 4% 2%
Tenosynovitis 3% 2% 0% 1% 2% 5% 1%
Dizziness 4% 5% 3% 6% 5% 7% 6%
Headache 7% 13% 11% 12% 21% 10% 8%
Paresthesia 2% 3% 1% 1% 2% 4% 3%
Bronchitis 7% 5% 2% 4% 7% 8% 7%
Increased Cough 3% 4% 5% 3% 6% 5% 7%
Respiratory 15% 21% 21% 20% 32% 27% 25%
Infection 3% 2% 1% 2% 1% 3% 3%
Pharyngitis 2% 3% 0% 0% 1% 2% 2%
Pneumonia 2% 5% 2% 4% 3% 2% 2%
Rhinitis Sinusitis 2% 5% 5% 0% 10% 1% 1%
Alopecia 10% 9% 1% 6% 6% 17% 10%
Eczema 2% 1% 1% 1% 1% 3% 2%
Pruritus 4% 5% 2% 3% 2% 6% 2%
Rash 10% 12% 7% 11% 9% 11% 10%
Dry Skin 2% 3% 2% 2% 0% 3% 1%
Urinary Tract Infection 5% 5% 7% 4% 2% 5% 6%
* Only 10% of patients in MN302 received folate. All patients in US301 received folate; none in MN301 received folate.
1 Includes all controlled and uncontrolled trials with leflunomide (duration up to 12 months).
2 Hypertension as a preexisting condition was overrepresented in all leflunomide treatment groups in phase III trials
3 In a meta-analysis of all phase II and III studies, during the first 6 months in patients receiving leflunomide, 10% lost 10-19 lbs (24 cases per 100 patient years) and 2% lost at least 20 lbs (4 cases/100 patient years). Of patients receiving leflunomide, 4% lost 10% of their baseline weight during the first 6 months of treatment.

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

In addition, the following adverse events have been reported in 1% to < 3% of the RA patients in the leflunomide treatment group in controlled clinical trials.

Body as a Whole: abscess, cyst, fever, hernia, malaise, pain, neck pain, pelvic pain;

Cardiovascular: angina pectoris, migraine, palpitation, tachycardia, varicose vein, vasculitis, vasodilatation;

Gastrointestinal: cholelithiasis, colitis, constipation, esophagitis, flatulence, gastritis, gingivitis, melena, oral moniliasis, pharyngitis, salivary gland enlarged, stomatitis (or aphthous stomatitis), tooth disorder;

Endocrine: diabetes mellitus, hyperthyroidism;

Hemic and Lymphatic System: anemia (including iron deficiency anemia), ecchymosis;

Metabolic and Nutritional: creatine phosphokinase increased, hyperglycemia, hyperlipidemia, peripheral edema;

Musculo-Skeletal System: arthrosis, bone necrosis, bone pain, bursitis, muscle cramps, myalgia, tendon rupture;

Nervous System: anxiety, depression, dry mouth, insomnia, neuralgia, neuritis, sleep disorder, sweating increased, vertigo;

Respiratory System: asthma, dyspnea, epistaxis, lung disorder;

Skin and Appendages: acne, contact dermatitis, fungal dermatitis, hair discoloration, hematoma, herpes simplex, herpes zoster, maculopapular rash, nail disorder, skin discoloration, skin disorder, skin nodule, subcutaneous nodule, ulcer skin;

Special Senses: blurred vision, cataract, conjunctivitis, eye disorder, taste perversion;

Urogenital System: albuminuria, cystitis, dysuria, hematuria, menstrual disorder, prostate disorder, urinary frequency, vaginal moniliasis.

Other less common adverse events seen in clinical trials include: 1 case of anaphylactic reaction occurred in Phase 2 following rechallenge of drug after withdrawal due to rash (rare); urticaria; eosinophilia; transient thrombocytopenia (rare); and leukopenia < 2000 WBC/mm3 (rare).

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

In post-marketing experience, the following have been reported:

Body as a whole: opportunistic infections, severe infections including sepsis that may be fatal;

Gastrointestinal: pancreatitis;

Hematologic: agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia;

Hypersensitivity: angioedema;

Hepatic: hepatitis, jaundice/cholestasis, severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal;

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

Nervous system: peripheral neuropathy;

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

Adverse Reactions (Pediatric Patients)

The safety of ARAVA was studied in 74 patients with polyarticular course juvenile rheumatoid arthritis ranging in age from 3-17 years (47 patients from the active-controlled study and 27 from an open-label safety and pharmacokinetic study). The most common adverse events included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness. Less common adverse events included anemia, hypertension, and weight loss. Fourteen pediatric patients experienced ALT and/or AST elevations, nine between 1.2 and 3-fold the upper limit of normal, five between 3 and 8-fold the upper limit of normal.

Drug Abuse And Dependence

ARAVA has no known potential for abuse or dependence.

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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