Trade Names:Arava- Tablet 10 mg- Tablet 20 mgApo-Leflunomide (Canada)PMS-Leflunomide (Canada)Sandoz Leflunomide (Canada)
An isoxazole immunomodulatory agent that inhibits dihydro-orotate dehydrogenase and has antiproliferative and anti-inflammatory activity.
The T max of active metabolite is 6 to 12 h. Without a loading dose (100 mg/3 days), steady-state plasma concentration would require nearly 2 mo of dosing. Plasma levels are dose-proportional. High-fat food does not affect absorption.
Steady-state Vd is 0.13 L/kg. Greater than 99.3% protein bound.
The specific site of metabolism is unknown. The major active metabolite responsible for all activity is A77 1726 (M1); 4-trifluor-methylaniline is the minor metabolite.
The t ½ is approximately 2 wk. Renally excreted as well as by direct biliary excretion. Renal excretion is more significant in the first 96 h. Eliminated in urine (43%) and feces (48%). Primary urinary metabolites are leflunomide glucoronide and oxanilic acid derivative of M1. Primary fecal metabolite is M1.
Studies have not been done; however, leflunomide is not recommended in these patients.Tobacco use
Tobacco use has a 38% increase in Cl over nonsmokers; however, no difference in clinical efficacy was seen between smokers and nonsmokers.
Treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms and to retard structural damage.
Pregnancy; standard considerations.
PO 100 mg every day for 3 days.Maintenance therapy
PO 20 mg every day. If dosing at 20 mg/day is not well-tolerated, the dose may be decreased to 10 mg/day.
Store at controlled room temperature (59° to 86°F); protect from light.
Decrease plasma leflunomide.Hepatotoxic drugs
May potentiate the hepatotoxicity of leflunomide.NSAIDs and tolbutamide
Free-fraction serum concentrations were increased by leflunomide.Rifampin
May increase leflunomide serum levels.
May cause hypophosphaturia. May cause an increase in uric acid excretion.
Hypertension; chest pain; palpitation; tachycardia; varicose vein; vasculitis; vasodilation.
Dizziness; headache; paresthesia; anxiety; depression; dry mouth; insomnia; neuralgia; neuritis; sleep disorder; vertigo; migraine.
Alopecia; eczema; pruritus; rash; dry skin; abscess; cyst; Stevens-Johnson syndrome and toxic epidermal necrolysis (rare, discontinue drug if symptoms occur).
Diabetes mellitus; hyperthyroidism.
Abdominal pain; anorexia; diarrhea; dyspepsia; gastroenteritis; nausea; mouth ulcer; vomiting.
Albuminuria; cystitis; dysuria; hematuria; menstrual disorder; prostate disorder; urinary frequency; vaginal moniliasis.
Abnormal liver enzymes.
Increased CPK; hyperglycemia; hyperlipidemia; hypokalemia.
Arthralgia; leg cramps; joint disorder; synovitis; tenosynovitis; arthrosis; bone necrosis; bone pain; bursitis; muscle cramps; myalgia; tendon rupture.
Bronchitis; increased cough; respiratory infection; pharyngitis; pneumonia; rhinitis; sinusitis; asthma; dyspnea; epistaxis; lung disorder.
Blurred vision; cataract; conjunctivitis; eye disorder; taste perversion.
Peripheral edema; weight loss; UTI; asthenia; flu syndrome; infection; injury, accident; pain; back pain; fever; hernia; malaise; neck pain; pelvic pain; increased sweating.
Contraindicated in pregnancy. Pregnancy must be excluded prior to initiation of therapy. Ensure reliable use of contraception in women with childbearing potential during therapy. Patient must avoid pregnancy prior to completion of the drug elimination procedure after leflunomide treatment.
Category X .
Do not use in breast-feeding mothers. It is not known if leflunomide is excreted in human milk.
No dosage adjustment is needed in patients older than 65 yr of age.
Renal function impairment; immunocompromise; bone marrow dysplasia; severe, uncontrolled infections; pre-existing hepatic disease.
Without the drug elimination procedure, it may take up to 2 yr to reach plasma M1 metabolite levels less than 0.02 mg/L because of individual variation in drug Cl. Recommended to achieve nondetectable plasma levels (less than 0.02 mg/L) after stopping treatment:
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