|Manufacturer:||BARR LABORATORIES, INC.|
Daily dosing of 20 mg is recommended for treatment of patients with RA.
A small cohort of patients (n=104), treated with 25 mg/day, experienced a greater incidence of side effects; alopecia, weight loss, liver enzyme elevations.
Doses higher than 20 mg/day are not recommended.
If dosing at 20 mg/day is not well tolerated clinically, the dose may be decreased to 10 mg daily.
Liver enzymes must be monitored and dose adjustments may be necessary (see WARNINGS, Hepatotoxicity).Due to the prolonged halflife of the active metabolite of leflunomide, patients should be carefully observed after dose reduction, since it may take several weeks for metabolite levels to decline.
Leflunomide Tablets are indicated in adults for the treatment of active rheumatoid arthritis (RA):to reduce signs and symptomsto inhibit structural damage as evidenced by X-ray erosions and joint space narrowingAspirin, nonsteroidal anti-inflammatory agents and/or low dose corticosteroids may be continued during treatment with leflunomide (see PRECAUTIONS, Drug Interactions, NSAIDs).The combined use of leflunomide with antimalarials, intramuscular or oral gold, D penicillamine, azathioprine or methotrexate has not been adequately studied (see WARNINGS, Immunosuppression Potential/Bone Marrow Suppression).
Leflunomide is contraindicated in patients with known hypersensitivity to leflunomide or any of the other components of leflunomide tablets.Leflunomide can cause fetal harm when administered to a pregnant woman.
Leflunomide, when administered orally to rats during organogenesis at a dose of 15 mg/kg, was teratogenic (most notably anophthalmia or microophthalmia and internal hydrocephalus).
The systemic exposure of rats at this dose was approximately 1/10 the human exposure level based on AUC.
Under these exposure conditions, leflunomide also caused a decrease in the maternal body weight and an increase in embryolethality with a decrease in fetal body weight for surviving fetuses.
In rabbits, oral treatment with 10 mg/kg of leflunomide during organogenesis resulted in fused, dysplastic sternebrae.
The exposure level at this dose was essentially equivalent to the maximum human exposure level based on AUC.
At a 1 mg/kg dose, leflunomide was not teratogenic in rats and rabbits.When female rats were treated with 1.25 mg/kg of leflunomide beginning 14 days before mating and continuing until the end of lactation, the offspring exhibited marked (greater than 90%) decreases in postnatal survival.
The systemic exposure level at 1.25 mg/kg was approximately 1/100 the human exposure level based on AUC.Leflunomide is contraindicated in women who are or may become pregnant.If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Leflunomide is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections.
In the event that a serious infection occurs, it may be necessary to interrupt therapy with leflunomide and administer cholestyramine or charcoal (see PRECAUTIONS, General, Need for Drug Elimination).
Medications like leflunomide that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections.
Rarely, severe infections including sepsis, which may be fatal, have been reported in patients receiving leflunomide.
Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid disease, may predispose patients to infection.There have been rare reports of pancytopenia, agranulocytosis and thrombocytopenia in patients receiving leflunomide alone.
These events have been reported most frequently in patients who received concomitant treatment with methotrexate or other immunosuppressive agents, or who had recently discontinued these therapies; in some cases, patients had a prior history of a significant hematologic abnormality.Patients taking leflunomide should have platelet, white blood cell count and hemoglobin or hematocrit monitored at baseline and monthly for six months following initiation of therapy and every 6 to 8 weeks thereafter.
If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly.
If evidence of bone marrow suppression occurs in a patient taking leflunomide, treatment with leflunomide should be stopped, and cholestyramine or charcoal should be used to reduce the plasma concentration of leflunomide active metabolite (see PRECAUTIONS, General, Need for Drug Elimination).In any situation in which the decision is made to switch from leflunomide to another anti-rheumatic agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds.Leflunomide washout with cholestyramine or charcoal may decrease this risk, but also may induce disease worsening if the patient had been responding to leflunomide treatment.