Lefno

Leflunomide

Active RA & psoriatic arthritis in adults.

Loading dose: 100 mg once daily for 3 days. RA Initially 10 mg or 20 mg depending on severity of disease. Maintenance dose: 10-20 mg once daily. Psoriatic arthritis Maintenance dose: 20 mg once daily.

May be taken with or without food: Swallow whole w/ sufficient amount of liqd.

Hypersensitivity to leflunomide & principal active metabolite teriflunomide. Patients w/ severe immunodeficiency states eg, AIDS; significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia due to causes other than RA or psoriatic arthritis; serious infections; severe hypoproteinaemia eg, in nephrotic syndrome. Liver function impairment. Moderate to severe renal insufficiency. Women of childbearing potential not using reliable contraception during treatment. Pregnancy & lactation.

Discontinue leflunomide & any concomitant myelosuppressive treatment & initiate washout procedure in case of severe haematological reactions including pancytopenia; skin &/or mucosal reactions; peripheral neuropathy. Discontinue treatment if ALT (SGPT) elevations between 2 & 3 fold ULN persist or if confirmed ALT elevations of >3 fold ULN are present; in case of ulcerative stomatitis; pulmonary symptoms eg, cough & dyspnoea. Interrupt treatment & administer washout procedure if serious infections occur. SJS, TEN & DRESS; ILD; peripheral neuropathy. Susceptibility to infections including opportunistic infections. Additive risks/increased side effects when switching to another DMARD w/o performing washout procedure. Evaluate patients for active & latent TB before starting treatment; monitor patients w/ history of TB. Check ALT (SGPT), CBC including differential WBC count & platelets before starting treatment & at least mthly intervals during 1st 6 mth, then every 6-8 wk thereafter; BP before starting therapy & periodically thereafter. Perform frequent haematological monitoring in patients w/ recent or concomitant treatment w/ immunosuppressive or haematotoxic drugs & when treatment is followed by such substances w/o washout period; history of relevant haematological abnormalities; relevant haematological abnormalities at baseline due to causes other than arthritic disease. Consider washout procedure if risk of haematological disorders is increased in patients w/ pre-existing anaemia, leucopenia, &/or thrombocytopenia & in patients w/ impaired bone marrow function or those at risk of bone marrow suppression. Administer cholestyramine or activated charcoal to clear A771726 from the body. Not recommended to use concomitantly w/ hepatotoxic or haematotoxic DMARDs (eg, MTX); teriflunomide. Avoid alcohol consumption during treatment. Additive or synergistic toxicity w/ antimalarials used in rheumatic diseases (eg, chloroquine & hydroxychloroquine), IM or oral gold, D-penicillamine, azathioprine & other immunosuppressives. Concomitant administration w/ phenytoin, warfarin, phenprocoumon & tolbutamide. May affect ability to drive & use machines. Not recommended in patients w/ significant hepatic impairment or pre-existing hepatic disease. Consider discontinuation & perform elimination procedure in males wishing to father a child. Not recommended for patients <18 yr.

Leucopenia; mild allergic reactions; increased CPK; paraesthesia, headache, dizziness; mild increase in BP; elevation of liver parameters [transaminases (especially ALT), γ-GT, alkaline phosphatase, bilirubin]; increased hair loss, eczema, rash including maculopapular rash, pruritus, dry skin; tenosynovitis; anorexia, wt loss, asthenia. TEN, SJS, DRESS.

Elevated liver enzymes w/ MTX. Increased prothrombin time w/ warfarin or other coumarin anticoagulant. Decreased plasma A771726 (active metabolite) conc w/ cholestyramine or activated charcoal powd. Increased peak A771726 levels w/ rifampicin. Increased mean C_max & AUC of CYP2C8 substrates eg, repaglinide, paclitaxel, pioglitazone or rosiglitazone; cefaclor; rosuvastatin; ethinylestradiol & levonorgestrel. Decreased mean C_max & AUC of caffeine. Reduced efficacy of CYP1A2 substrates eg, duloxetine, alosetron, theophylline & tizanidine. Decreased peak INR w/ warfarin. Concomitant use w/ live attenuated vaccines; organic anion transporter 3 substrates eg, benzylpenicillin, ciprofloxacin, indomethacin, ketoprofen, furosemide, cimetidine, zidovudine; BCRP substrates eg, topotecan, sulfasalazine, daunorubicin, doxorubicin; HMG-CoA reductase inhibitors eg, simvastatin, atorvastatin, pravastatin, nateglinide, repaglinide, rifampicin.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

L04AK01 - leflunomide ; Belongs to the class of dihydroorotate dehydrogenase (DHODH) inhibitors. Used as immunosuppressants.

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