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Arava

  • Generic Name: leflunomide
  • Brand Name: Arava
  • Drug Class: DMARDs, Other

Arava (Leflunomide) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

Arava Side Effects Center

Last reviewed on RxList 4/25/2019

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:

Tell your doctor if you have serious side effects of Arava including:

  • cough,
  • hair loss,
  • chest pain,
  • fast or pounding heartbeat,
  • increased thirst or urination,
  • muscle cramps or pain,
  • mental/mood changes,
  • vision changes,
  • easy bruising or bleeding,
  • unusual growths or lumps,
  • swollen glands (lymph nodes),
  • unexplained weight loss, or
  • unusual tiredness.

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. Breastfeeding 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.

 

Arava Consumer Information

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

Call your doctor at once if you have:

  • signs of infection--sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing;
  • sudden chest pain or discomfort, wheezing, dry cough, feeling short of breath;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • numbness, tingling, or burning pain in your hands or feet;
  • liver problems--nausea, upper stomach pain, itching, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • nausea, diarrhea, stomach pain;
  • headache;
  • abnormal liver function tests;
  • thinning hair;
  • back pain;
  • weakness;
  • rash; or
  • high blood pressure.

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)

 

Arava Professional Information

SIDE EFFECTS

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)		 PL
(n=118)		 MTX 7.5 - 15 mg/wk
(n=182)		 ARAVA 20mg/day
(n=133)		 PL
(n=92)		 SSZ 2.0 g/day
(n=133)		 ARAVA 20 mg/day
(n=501)		 MTX 7.5 - 15 mg/wk
(n=498)
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
(N=315)		 PL
(N=210)		 SSZ 2.0g/day
(N=133)		 MTX 7.5 - 15 mg/wk
(N=182)		 ARAVA 20 mg/day
(N=501)		 MTX 7.5 - 15 mg/wk
(N=498)		 ARAVA
(N=1339)2
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)

&Copy; Arava Patient Information is supplied by Cerner Multum, Inc. and Arava Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.