Also found in: Dictionary, Thesaurus, Wikipedia.
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.
• 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.
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)
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
• 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.
• 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.
Arava™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.
leflunomide; 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
asava. See also arista.