OVERDOSE
There is no human experience regarding leflunomide overdosage.
In mouse and rat acute toxicology studies, the minimally
toxic dose for oral leflunomide was 200-500 mg/kg and
100 mg/kg respectively (approximately >350 times the
maximum recommended human dose respectively).
In the event of a significant overdose or toxicity, cholestyramine
or charcoal administration is recommended to accelerate
elimination (see PRECAUTIONS: General - Need for Drug
Elimination).
CONTRAINDICATIONS
See BOXED
CONTRAINDICATIONS
AND WARNINGS.
ARAVA is contraindicated in patients with known hypersensitivity
to leflunomide or any of the other components of ARAVA.
ARAVA 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.
ARAVA 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.
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