Leflunomide

The active metabolite of leflunomide, the ring-opened drug A771726, inhibits dihydroorotate dehydrogenase (DHOD) which is the key enzyme of the de novo pyrimidine synthesis. Inhibition of synthesis stops proliferation of activated lymphocytes. The leflunomide derivative FK778 which shows similar therapeutic efficacy but shorter half-life is investigated in clinical trials. 

Low-dose methotrexate is used for treatment of rheumatoid arthritis despite side effects such as disorders of the gastrointestinal tract and the liver. Leflunomide is also approved for this indication, however, hepatoxicity limits its use as first option. 

QHiqO 141-97-9) see Aminophenazone Baclofen Cefotaxime Ceftazidime Chloroquine Cloricromen Cloxacillin Dipyridamole Felodipine Flutoprazepam Hymecromone Kawain Lacidipine Leflunomide Methylthiouracil Nevirapine Nitrendipine Oxacillin Pentoxifylline Propyphenazone Sulfamerazine acetoacetic acid 4-(trifluoromethyl)anilide (C H (,F3N02 351-87-1) see Leflunomide acetoacetyl chloride... 

C4H4O2 674-82-8) see Aranidipine Bamidipine Benidipine Butoctamide Efonidipine hydrochloride ethanol Epirizole Ketazolam Leflunomide Lercanidipine hydrochloride Manidipine Nimodipine Orotic acid diloxanide... 

Leflunomide (Arava) 100 mg daily for 3 days then 20 mg daily Oral 4-12 weeks Hepatotoxicity, D, N, HTN, rash, HA, abdominal pain CBC, creatinine, LFTs q mo. for 6 mo. then q 4-8 weeks Monitor for signs of infection Avoid alcohol Use contraception if childbearing potential... 

Efavirenz, nevirapine Epristeride, finasteride, dutasteride Fluoro uracil Leflunomide... 

Leflunomide Oral 100 mg daily for 3 Baseline ALT, CBC with plate- CBC with platelets and... 

Leflunomide Hepatitis, Gl distress, alopecia Nausea/vomiting gastritis, diarrhea, hair... 

Leflunomide (Arava) inhibits pyrimidine synthesis, which reduces lymphocyte proliferation and modulation of inflammation. Its efficacy for RA is similar to that of MTX. 

The drug may cause liver toxicity and is contraindicated in patients with preexisting liver disease. The ALT should be monitored monthly initially and periodically thereafter. Leflunomide may cause bone marrow toxicity a complete blood cell count with platelets is recommended monthly for 6 months and then every 6 to 8 weeks thereafter. It is teratogenic and should be avoided during pregnancy. 

Of interest here is that certain drugs and prodrugs that contain an isoxazole ring are metabolized to a cyano enol, e.g., leflunomide (11.122, R = CF3, R = H), a prodrug of the potential anti-arthritic agent 2-cyano-3-hydroxy-A-[4-(trifluoromethyl)phenyl]but-2-enamide (11.123). After oral administration of 50 mg/kg of 11.122 to rats, the plasma concentration of the prodrug peaked at 1 pg/ml and dropped rapidly, whereas the concentration of the active metabolite 11.123 was maintained at ca. 100 pg/ml for 24 h [147]. This... 

Strand, V., Cohen, S., Schiff, M., et al. (1999) Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Archives of Internal Medicine. 159, 2542-2550. 

Dietrich S, Kramer OH, Hahn E et al (2012) Leflunomide induces apoptosis in fludarabine-resistant and clinically refractory CLL cells. Clin Cancer Res 18 417-4 31... 

Leflunomide is an immunomodulatory dmg inhibiting dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine synthesis. It has also anti-inflammatory effects. Leflunomide is able to slow progression of the disease and to cause re-mission/relief of symptoms of rheumatoid arthritis and psoriatic arthritis such as joint tenderness and decreased joint and general mobility in patients. The combined use of leflunomide with methotrexate may... 

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