Leflunomide

Leflunomide

Clinical data
Trade names	Arava, Arabloc, Lunava, Repso, Elafra
AHFS/Drugs.com	Monograph
MedlinePlus	a600032
License data	EU EMA: Arava US FDA: Leflunomide
Pregnancy category	AU: X (High risk) US: X (Contraindicated)
Routes of administration	Oral (tablets)
ATC code	L04AA13 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	80%
Protein binding	>99%
Metabolism	GI mucosa and liver
Biological half-life	14–18 days
Excretion	Faeces (48%), urine (43%)
Identifiers
IUPAC name 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-carboxamide
CAS Number	75706-12-6 Y
PubChem CID	3899
IUPHAR/BPS	6825
DrugBank	DB01097 Y
ChemSpider	3762 Y
UNII	G162GK9U4W
KEGG	D00749 Y
ChEBI	CHEBI:6402 Y
ChEMBL	CHEMBL960 Y
ECHA InfoCard	100.123.883
Chemical and physical data
Formula	C12H9F3N2O2
Molar mass	270.207 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(Nc1ccc(cc1)C(F)(F)F)c2c(onc2)C
InChI InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18) Y Key:VHOGYURTWQBHIL-UHFFFAOYSA-N Y

Leflunomide (original brand name Arava) is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Rheumatoid arthritis and psoriatic arthritis are the only indications that have received regulatory approval. Arava was developed by Sanofi Aventis and approved by the U.S. Food and Drug Administration in 1998. Clinical studies regarding the following diseases have been conducted:

The dose-limiting side effects are liver damage, lung disease and immunosuppression. The most common side effects (occurring in >1% of those treated with it) are, in approximately descending order of frequency: diarrhea, respiratory tract infections, hair loss, high blood pressure, rash, nausea, bronchitis, headache, abdominal pain, abnormal liver function tests, back pain, indigestion, urinary tract infection, dizziness, infection, joint disorder, itchiness, weight loss, loss of appetite, cough, gastroenteritis, pharyngitis, stomatitis, tenosynovitis, vomiting, weakness, allergic reaction, chest pain, dry skin, eczema, paraesthesia, pneumonia, rhinitis, synovitis, cholelithiasis and shortness of breath. Whereas uncommon side effects (occurring in 0.1-1% of those treated with the drug) include: constipation, oral thrush, stomatitis, taste disturbance, thrombocytopenia and hives. Rarely (in 0.1% of those treated with it) it can cause:anaphylaxis, angiooedema, anaemia, agranulocytosis, eosinophilia, leucopenia, pancytopenia, vasculitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, cutaneous lupus erythematosus, severe infection, interstitial lung disease, cirrhosis and liver failure.