Adult: Loading dose (optional): 100 mg once daily for 3 days. May omit the loading dose to decrease the risk of adverse effects, especially in patients with increased risk for haematologic or hepatic toxicity. Maintenance: 10-20 mg once daily. Dosing discontinuation and initiation of washout procedure may be required according to individual safety and tolerability (refer to detailed product guidelines).
Oral Psoriatic arthritis
Adult: Loading dose (optional): 100 mg once daily for 3 days. May omit the loading dose to decrease the risk of adverse effects, especially in patients with increased risk for haematologic or hepatic toxicity. Maintenance: 20 mg once daily. Dosing discontinuation and initiation of washout procedure may be required according to individual safety and tolerability (refer to detailed product guidelines).
What are the brands available for Leflunomide in Hong Kong?
Significantly impaired bone marrow function or significant neutropenia, leucopenia, thrombocytopenia and anaemia due to causes other than rheumatoid or psoriatic arthritis; severe hypoproteinaemia; serious infection, severe immunodeficiency states (e.g. AIDS). Hepatic and moderate to severe renal impairment. Pregnancy and lactation.
Special Precautions
Patient with new or history of recurrent infections, conditions that increase predisposition to infections, and chronic, localised or latent infections; history of interstitial lung disease (ILD). Teriflunomide (active metabolite) is slowly eliminated in the body and serious adverse effects may occur even after treatment discontinuation; therefore, a washout or accelerated drug elimination procedure may be required. Washout procedure using colestyramine or activated charcoal is recommended in patients who experience severe adverse reactions, if pregnancy occurs during therapy, or before switching to another DMARD; after the procedure, verify the teriflunomide plasma concentrations (<0.02 mg/L) by 2 separate tests at least 14 days apart. Refer to individual product guidelines for the detailed procedure. Concomitant use with live vaccines. Mild renal impairment.
Adverse Reactions
Significant: Abnormal LFTs (particularly increased ALT and AST), haematologic effects (e.g. agranulocytosis, pancytopenia, thrombocytopenia); increased susceptibility to infection, including opportunistic infections (particularly TB, Pneumocystis jirovecii pneumonia, or aspergillosis); mild to moderate diarrhoea; sensorimotor and peripheral neuropathy; increased risk of lymphoproliferative malignancy; skin ulcers, pustular psoriasis, exacerbation of psoriasis; severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Rarely, pulmonary hypertension. Gastrointestinal disorders: Nausea, abdominal pain, oral mucosal disorders (e.g. aphthous stomatitis, mouth ulceration); colitis, including microscopic colitis (e.g. lymphocytic colitis, collagenous colitis). General disorders and administration site conditions: Asthenia. Immune system disorders: Hypersensitivity reactions. Investigations: Increased creatine phosphokinase, increased blood pressure; weight loss. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Tenosynovitis, back pain. Nervous system disorders: Headache, dizziness, paraesthesia. Respiratory, thoracic and mediastinal disorders: Bronchitis, rhinitis. Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus, dry skin. Potentially Fatal: New-onset or worsening of pre-existing ILD. Rarely, severe liver injury (e.g. liver failure and hepatic necrosis), severe infections (e.g. sepsis).
Patient Counseling Information
Women of childbearing potential must use effective contraception during and for up to 2 years after stopping the treatment. If contraception for up to 2 years is not feasible after treatment discontinuation, a washout procedure may be initiated; continue using effective contraception and wait until teriflunomide is undetectable in the blood. Men with female partners of childbearing potential should use proven birth control methods during treatment; for men who wish to father a child, a washout procedure may be initiated after treatment discontinuation and wait until teriflunomide is undetectable in the blood.
Monitoring Parameters
Exclude pregnancy in women of reproductive potential prior to treatment initiation. Perform active and latent TB screening before starting the therapy. Obtain CBC with differential and hepatic function (particularly serum ALT) at baseline, every 2 weeks during the 1st 6 months of therapy, then every 6-8 weeks thereafter. Monitor blood pressure before and periodically during treatment. Assess for signs of new-onset or worsening pulmonary symptoms, severe infection, hepatic dysfunction, and hypertension.
Overdosage
Symptoms: Diarrhoea, nausea, abdominal pain, increased liver enzymes, pruritus, rash, anaemia, and leucopenia. Management: Symptomatic and supportive treatment. Administer activated charcoal susp via nasogastric tube or colestyramine to rapidly eliminate the drug.
Drug Interactions
Increased risk of hepatotoxicity and haematologic toxicity with methotrexate, other DMARDs, and other hepatotoxic or haematotoxic drugs. May increase the risk of infection with live vaccines. May result in rapid and significantly reduced teriflunomide plasma concentrations with colestyramine and activated charcoal. May increase or decrease prothrombin time with warfarin. May increase the plasma levels of teriflunomide with rifampicin. May increase the serum concentrations of CYP2C8 substrates (e.g. repaglinide, paclitaxel, pioglitazone), OATPB1B1/1B3 substrates (e.g. rosuvastatin, nateglinide), and organic anion transporter 3 (OAT3) substrates (e.g. cefaclor, ciprofloxacin, indometacin, ketoprofen, furosemide, cimetidine). May decrease the serum levels of agents metabolised by CYP1A2 (e.g. caffeine, theophylline, duloxetine, tizanidine). May elevate the systemic exposure of ethinylestradiol and levonorgestrel.
Food Interaction
May cause additive hepatotoxic effects with alcohol.
Lab Interference
May result in falsely reduced ionised Ca levels depending on the type of analyser used (e.g. blood gas analyser).
Action
Description: Mechanism of Action: Leflunomide, a prodrug, is an immunomodulatory agent and a disease-modifying anti-rheumatic drug (DMARD). Its active metabolite inhibits pyrimidine synthesis by blocking the human dihydroorotate dehydrogenase (DHODH) enzyme, leading to the antiproliferative and anti-inflammatory effects. Pharmacokinetics: Absorption: Bioavailability: Approx 82-95%. Time to peak plasma concentration: 6-12 hours (teriflunomide). Distribution: Distributes into semen (teriflunomide). Plasma protein binding: >99%, mainly to albumin (teriflunomide). Metabolism: Rapidly converted into the active metabolite, teriflunomide (A771726) via first-pass metabolism in the liver and gut wall; further metabolised to other minor metabolites. Undergoes enterohepatic recycling. Excretion: Via faeces (37.5%); urine (22.6%). Elimination half-life: Mean: Approx 18-19 days.
Chemical Structure
Leflunomide Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3899, Leflunomide. https://pubchem.ncbi.nlm.nih.gov/compound/Leflunomide. Accessed Nov. 26, 2024.
L04AK01 - leflunomide ; Belongs to the class of dihydroorotate dehydrogenase (DHODH) inhibitors. Used as immunosuppressants.
References
Anon. Leflunomide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/11/2024.Arava 10 mg and 20 mg Film-coated Tablets (Sanofi-Aventis [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/11/2024.Arava Tablet, Film Coated (Sanofi-Aventis U.S. LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/11/2024.Brayfield A, Cadart C (eds). Leflunomide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2024.Joint Formulary Committee. Leflunomide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2024.Leflunomide Mylan 20 mg Film-coated Tablets (Generics UK Ltd. Trading as Mylan). MHRA. https://products.mhra.gov.uk. Accessed 04/11/2024.Leflunomide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 04/11/2024.Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. Arava 10 mg and 20 mg Film-coated Tablets data sheet 20 June 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 04/11/2024.
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