Lefno

Adults w/ active RA & psoriatic arthritis.

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

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

Hypersensitivity (especially previous SJS, TEN, erythema multiforme) to leflunomide or 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. Women of childbearing potential not using reliable contraception. Hepatic impairment. Moderate to severe renal insufficiency. Pregnancy & lactation.

Discontinue use & initiate washout procedure if ALT elevations of >2-fold times ULN persist or >3-fold times ULN are present; in case of severe haematological reactions including pancytopenia; as soon as skin &/or mucosal reactions are observed which raise suspicion of SJS or TEN; in event that severe, uncontrolled infections occur; if peripheral neuropathy develops. Discontinue use in case of ulcerative stomatitis. Risk of serious undesirable effects even if treatment has been stopped. Reports of pustular psoriasis & worsening of psoriasis; ILD & rare cases of pulmonary HTN; rare cases of progressive multifocal leukoencephalopathy; colitis including microscopic colitis. Switching to another DMARD (eg, MTX) w/o washout procedure may raise possibility of additive risks & may result in increased side effects (closer monitoring is recommended in initial phase after switching). Check ALT & perform CBC including differential WBC count & platelets prior to initiation & during the 1st 6 mth of treatment & every 8 wk thereafter. Maintain monitoring of liver enzymes after discontinuation until levels have normalised. Evaluate patients for active & inactive (latent) TB prior to starting treatment & carefully monitor patients w/ history of TB due to possible reactivation of infection. Check BP prior to start of treatment & periodically thereafter. Not advisable to be co-administered w/ hepatotoxic or haematotoxic DMARDs eg, MTX; antimalarials (eg, chloroquine & hydroxychloroquine), IM or oral gold, D-penicillamine, azathioprine & other immunosuppressives including TNF α-inhibitors; teriflunomide. Avoid alcohol consumption during treatment. Interference w/ determination of ionised Ca levels. Refrain from driving cars & using machines in case of side effects eg, dizziness. Possible male-mediated foetal toxicity; consider discontinuation & perform washout procedure in males wishing to father a child. Women of childbearing potential must use effective contraception during & up to 2 yr after treatment (waiting period before becoming pregnant) or up to 11 days after treatment (washout period for 11 days). Not recommended in childn <18 yr.

Leucopenia; mild allergic reactions; increased creatine phosphokinase; paraesthesia, headache, dizziness, peripheral neuropathy; mild increase in BP; colitis including microscopic colitis (eg, lymphocytic colitis), collagenous colitis, diarrhoea, nausea, vomiting, oral mucosal disorders (eg, aphthous stomatitis, mouth ulceration), abdominal pain; elevated liver parameters [transaminases (especially ALT), less often γ-glutamyl transferase, alkaline phosphatase, bilirubin]; increased hair loss, eczema, rash (including maculopapular rash), pruritus, dry skin; tenosynovitis; anorexia, wt loss, asthenia.

Increased side effects w/ recent or concomitant use of hepatotoxic or haematotoxic drugs or when treatment is followed by such drugs w/o washout period. Vaccination w/ live attenuated vaccines is not recommended. Increased prothrombin time w/ warfarin. Rapid & significant decrease in plasma A771726 (active metabolite) conc w/ cholestyramine or activated charcoal powd. Increased peak A771726 levels w/ rifampicin (non-specific CYP450 inducer). May increase exposure of CYP2C8 substrates eg, repaglinide, paclitaxel, pioglitazone or rosiglitazone; OAT3 substrates eg, cefaclor, benzylpenicillin, ciprofloxacin, indomethacin, ketoprofen, furosemide, cimetidine, MTX, zidovudine; BCRP substrates eg, MTX, topotecan, sulfasalazine, daunorubicin, doxorubicin; HMG-CoA reductase inhibitors eg, rosuvastatin, simvastatin, atorvastatin, pravastatin, nateglinide, MTX, repaglinide, rifampicin; ethinylestradiol & levonorgestrel. Decreased mean C_max & AUC of caffeine. Reduced efficacy of CYP1A2 substrates eg, duloxetine, alosetron, theophylline & tizanidine. Decreased peak INR w/ warfarin.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

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

Rx