Leflunomide

Oral
Rheumatoid arthritis, Psoriatic arthritis

Mild: No dosage adjustment needed. Moderate to Severe: Contraindicated.

Contraindicated.

May be taken with or without food.

Hepatic impairment, moderate and severe renal impairment, compromised immune function including bone marrow dysplasia or severe uncontrolled infection, severe hypoproteinaemia; concurrent vaccination w/ live vaccines. Pregnancy and lactation.

Mild renal impairment. Patient w/ history of TB due to the possibility of reactivation of the infection.

HTN, diarrhoea, upper respiratory tract infections, thrombocytopenia, leukopenia, pancytopenia, agranulocytosis, headache, alopecia, dry skin, eczema, erythema multiforme, hypokalaemia, weight loss, asthenia, anxiety, paraesthesia, synovitis, joint disorder, peripheral neuropathy, mild hyperlipidaemia, interstitial lung disease, vasculitis.
Potentially Fatal: Hepatotoxicity, sepsis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis.

Monitor BP and liver enzyme values prior to initiation and periodically during therapy.

Symptoms: Abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash. Management: Administer cholestyramine or charcoal to hasten elimination of the drug. Supportive and symptomatic treatment should also be initiated and observed patient closely.

Cholestyramine and activated charcoal may decrease plasma concentration of active metabolite. Concurrent use of methotrexate and other hepatotoxic drugs may increase the risk of hepatotoxicity. Rifampicin increases serum levels of the active metabolite.
Potentially Fatal: May enhance the adverse effects of live vaccines.

Avoid alcohol due to increased risk of hepatotoxicity. Echinacea may reduce the therapeutic effect of leflunomide.

Description:
Mechanism of Action: Leflunomide is an immunomodulating agent and DMARD. It inhibits pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase enzyme activity resulting in antiproliferative and anti-inflammatory effects.
Pharmacokinetics:
Absorption: Bioavailability: Approx 82-95%. Time to peak plasma concentration (active metabolite): 6-12 hr.
Distribution: Volume of distribution: 0.13 L/kg. Plasma protein binding (active metabolite): 99% (mainly albumin).
Metabolism: Rapidly converted to active metabolite A77 1726 in GI mucosa and the liver.
Excretion: Via urine (approx 43% as glucuronides) and faeces (approx 48%). Elimination half-life (active metabolite): Approx 14-18 days.

Store at 25°C.

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