Also found in: Dictionary, Thesaurus, Wikipedia.


Apo-Leflunomide (CA), Arava, Novo-Leflunomide (CA), PMS-Leflunomide (CA), Sandoz Leflunomide (CA)

Pharmacologic class: Immune modulator

Therapeutic class: Antirheumatic

Pregnancy risk category X

FDA Box Warning

• Rule out pregnancy before starting therapy. Drug is contraindicated in pregnant women and in women of childbearing age who don't use reliable contraception. Caution patient to avoid pregnancy during therapy or before completing drug elimination procedure after treatment.

• Be aware that severe liver injury, including fatal liver failure, has been reported in some patients treated with leflunomide. Know that patients with preexisting acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) level of more than two times the upper limit of normal (ULN) before initiating treatment, shouldn't be treated with leflunomide. Use caution when giving drug with other potentially hepatotoxic drugs. Monitor ALT level at least monthly for first 6 months of therapy, and every 6 to 8 weeks thereafter. If ALT elevation is more than three times ULN, interrupt therapy while investigating the probable cause of the ALT elevation by close observation and additional tests. If ALT elevation is likely leflunomide-induced, start cholestyramine washout and monitor liver tests weekly until normalized. If leflunomide-induced liver injury is unlikely (because another probable cause has been found), resumption of therapy may be considered.


Inhibits T-cell pyrimidine biosynthesis, tyrosine kinases, and dihydroorotate dehydrogenase, blocking structural damage caused by inflammatory response to autoimmune process. Also shows analgesic, antipyretic, and histamine-blocking activity.


Tablets: 10 mg, 20 mg, 100 mg

Indications and dosages

Active rheumatoid arthritis

Adults: 100 mg P.O. daily for 3 days, then a maintenance dosage of 20 mg daily. If intolerance occurs, decrease to 10 mg daily.

Dosage adjustment

• Hepatic enzyme elevations


• Hypersensitivity to drug or its components
• Women who are or may become pregnant


Use cautiously in:
• renal insufficiency
• patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections (not recommended)
• new-onset or worsening pulmonary symptoms
• concurrent use of potentially hepatotoxic drugs
• concurrent use of live-virus vaccines (not recommended)
• men attempting to father a child
• breastfeeding patients
• children younger than age 18.


• Before starting drug, screen patients for latent tuberculosis (TB) infection with a tuberculin skin test. Treat patients who test positive for TB with standard medical practice before starting leflunomide.
• Obtain baseline platelet and white blood cell (WBC) counts, and hemoglobin or hematocrit.
• Check patient's blood pressure before starting leflunomide
• Give with or without food.
• Be aware that drug has a long half-life. To eliminate from bloodstream, give 8 g cholestyramine P.O. t.i.d. for 11 days.

Adverse reactions

CNS: headache, dizziness, asthenia

CV: chest pain, hypertension

EENT: rhinitis, sinusitis, pharyngitis

GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia, gastroenteritis, mouth ulcers, anorexia

GU: urinary tract infection

Hematologic: pancytopenia, agranulocytosis, thrombocytopenia (rare)

Hepatic: hepatotoxicity

Metabolic: hypokalemia

Musculoskeletal: joint pain or disorders, back pain, leg cramps, synovitis, tenosynovitis

Respiratory: bronchitis, increased cough, pneumonia, respiratory infection, fatal interstitial lung disease

Skin: alopecia, rash, dry skin, eczema, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis

Other: weight loss, pain, infection, allergic reactions, flulike symptoms


Drug-drug.Activated charcoal, cholestyramine: rapid, steep drop in blood level of leflunomide's active metabolite

Methotrexate, other hepatotoxic drugs: increased risk of hepatotoxicity

Rifampin: increased blood level of leflunomide's active metabolite

Drug-diagnostic tests.Alanine aminotransferase (ALT), aspartate aminotransferase: increased levels

Hematocrit, hemoglobin, platelets, WBCs: decreased levels

Patient monitoring

• Check vital signs closely.
• Monitor platelet and WBC counts and hemoglobin or hematocrit monthly for 6 months after initiation of therapy and every 6 to 8 weeks thereafter. If evidence of bone marrow suppression occurs, discontinue drug and treat as indicated to reduce plasma concentration of leflunomide's active metabolite.

Watch for signs and symptoms of hepatotoxicity.

Be aware that rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in patients receiving leflunomide. If patient develops either condition, discontinue drug by using the recommended drug elimination procedure.
• Periodically assess cardiovascular status, including blood pressure, carefully to detect adverse reactions.
• Be aware that interstitial lung disease has been reported during leflunomide therapy and has been associated with fatal outcomes. New-onset or worsening pulmonary symptoms, such as cough and dyspnea with or without associated fever, may be cause for discontinuing drug and for further investigation as appropriate. If stopping drug is necessary, consider initiation of wash-out procedures.
• Monitor electrolyte levels.
• Monitor ALT level at least monthly for 6 months after starting drug, and every 6 to 8 weeks thereafter. If ALT level is more than three times the upper limit of normal, interrupt therapy while investigating the probable cause of the ALT elevation by close observation and additional tests. If leflunomide therapy is likely cause, start cholestyramine washout and monitor liver tests weekly until normalized. If leflunomide-induced liver injury is unlikely because another probable cause has been found, consider resuming drug therapy.
• Stay alert for signs and symptoms of infection. If a serious infection occurs, it may be necessary to interrupt therapy and administer cholestyramine or charcoal, as indicated.
• Observe patient closely after dosage reduction. Metabolite levels may take several weeks to fall.

Patient teaching

• Tell patient he may take with or without food.

Advise patient to immediately report unusual tiredness or yellowing of skin or eyes.

Instruct patient to recognize and report signs or symptoms of infection, respiratory problems, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
• Advise patient to avoid vaccination with live-virus vaccines.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

Inform female of childbearing age that drug may harm fetus. Tell her to contact prescriber immediately if she suspects pregnancy.
• Caution female not to breastfeed without consulting prescriber.
• Advise male planning to father a child to consult prescriber, because drug may harm fetus.
• Tell patient he'll undergo regular blood testing to check liver function.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.


Leflunomide Rheumatology An agent used to manage rheumatoid arthritis in adults and slow structural damage as evidenced by bone erosion and joint-space narrowing. See Rheumatoid arthritis.


; Arava long-acting disease-modifying antirheumatic drug of similar efficacy to methotrexate and sulfasalazine; acts on the immune system, is bone marrow-toxic, and increases patient predisposition to infection and malignancy

arava (äˑ·r·v),

n in Ayurveda, a method of medicine preparation in which an alcohol-based herbal tincture is created through natural fermentation. Herbal juices are mixed with raw sugar (jaggery) and dried forest-flame bush flowers (which contain yeast). Also called
asava. See also arista.
References in periodicals archive ?
Founded in 2006, Arava Power is a pioneer in the field of solar energy in Israel, leading the way in developing the industry and building numerous solar projects both in Israel's Negev and Arava regions.
Arava Power is to build a 40-megawatt solar field on 60 hectares of Kibbutz Ketura land.
To build these fields, Arava Power secured over $200 million in funding from sources including Bank Hapoalim, Migdal Insurance and the Jewish National Fund; received provisional licenses; and signed an agreement with Israel Electric Corporation to distribute the energy generated.
Since I can remember back, I was always inside different houses and buildings, looking at all types of architecture," Arava recalled.
The conduit is planned to run the length of the Arava Valley, which is known for seismic activity and flash flooding.
I misunderstood the leaders of the Arava Institute because I didn't realize to what degree the Jewish National Fund was supporting Arava.
From Israel and Jordan, the Arava & Wadi Araba communities who are engaged in agricultural activities in the area, the tourist industry that is flouring along the coast in Dead Sea, and chemical producing industries that are thriving along the coasts have genuine concerns about the environmental impact of the project, since they would be directly affected by the benefits or otherwise of the project.
Clashes and exchanges of fire between groups of youths took place in Osh and the neighbouring districts of Karassu, Arava and Uzgen," Farid Niyazov, a government spokesman, said.
The study was conducted at the Shezaf Nature Reserve during April 2006 to July 2009 in the southern part of Israel, ~30 km south of the Dead Sea in the Arava Rift Valley between the settlements of Hazeva (30[degrees] 46' N, 35[degrees] 16' E) and Ein Yahav (30[degrees] 45' N, 35[degrees] 15' E).
Algatechnologies, a leading manufacturer of AstaPure natural astaxanthin, is located in Israel's Arava desert.
CDATA[ Police are investigating the suspicion that a truck driver fell asleep on the wheel, plowing into a family's minivan on Arava road.
On the eve of the peace-signing ceremony at the Arava border crossing, 82 percent of the Jordanian population (including Palestinians) supported the agreement and praised at length the planned economic and other cooperation.