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MEDICINE MONOGRAPH CODE: [7.23] ID: TIP-MED-000125

Leflunomide

Active Ingredient / Scientific Identity: Leflunomide • Class: Dihydroorotate Dehydrogenase (DHODH) Pyrimidine Synthesis Inhibitor DMARD (Schedule H)

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THE INDIAN PHARMACIST — Educational Reference Sheet
Profile: Leflunomide ([7.23] | ID: TIP-MED-000125) • Last Reviewed: 2026-11-10
Source URL: https://theindianpharmacist.com/medicine/7-23-leflunomide/
Generic / Entity NameLeflunomide ([7.23])
Verified Indian Brands / RefGeneric Compendial Entry (No Commercial Brand Claimed)
Pharmacological ClassDihydroorotate Dehydrogenase (DHODH) Pyrimidine Synthesis Inhibitor DMARD (Schedule H)
Available Dosage FormsTablets: 10 mg, 20 mg
Regulatory ClassificationSchedule H Prescription Drug (To be sold by retail on the prescription of a Registere
Key Warning & Review DateRenal: Avoid in moderate-to-severe CKD. Hepatic: Contraindicated if baseline ALT >2x ULN; if ALT >3x ULN, STOP Leflunomide an
Reviewed: 2026-11-10
Safety Matrix:⚖️ Legal Status: Schedule H Prescription Drug (To be sold by retail o✔️ Standard Clinical Dispensing Precautions

1. Clinical & Scientific Overview

Leflunomide (TIP-MED-000125, Reference Code [7.23]) is classified under Pain, Inflammation, Rheumatology & Gout Medicines (Ch 07) as a Dihydroorotate Dehydrogenase (DHODH) Pyrimidine Synthesis Inhibitor DMARD (Schedule H). Within the Indian regulatory and compendial framework, it is governed under Schedule H Prescription Drug (To be sold by retail on the prescription of a Registered Medical Practitioner only — Drugs Rules 1945).

Verified Indian Market Examples / Compendial Status:
Representative Indian Market Examples (Edition 2.7 Ch 07 [7.23], p. 90): Lefno (Ipca), Arava (Sanofi), Lefra (Torrent), Rumalef (Zydus) — Strengths & Dosage Forms: Tablets: 10 mg, 20 mg
Representative Indian Market Examples (Edition 2.7 Ch 07 [7.23], p. 90): Lefno (Ipca), Arava (Sanofi), Lefra (Torrent), Rumalef (Zydus) — Strengths & Dosage Forms: Tablets: 10 mg, 20 mg
Dosage Forms & Available Strengths:
Tablets: 10 mg, 20 mg
Routes: Oral / Parenteral / Topical as specified by formulation

3. Mechanism of Action & Pharmacodynamics

Dihydroorotate Dehydrogenase (DHODH) Pyrimidine Synthesis Inhibitor DMARD (Schedule H) acting on target receptor/enzyme pathways in Pain, Inflammation, Rheumatology & Gout Medicines (Ch 07): clinical efficacy is mediated via Dihydroorotate Dehydrogenase (DHODH) Pyrimidine Synthesis Inhibitor DMARD (Schedule H) for Moderate-to-severe active Rheumatoid Arthritis and Psoriatic Arthritis (as alternative or add-on when Methotrexate is not tolerated or partially effective).

4. Therapeutic Indications & Evidence-Supported Uses

  • Moderate-to-severe active Rheumatoid Arthritis and Psoriatic Arthritis (as alternative or add-on when Methotrexate is not tolerated or partially effective)

🇮🇳 Jurisdiction & Indication Note: Indications and schedules reflect Indian compendial and regulatory records (CDSCO / Indian Pharmacopoeia & NFI / NLEM 2022). Where international reference labels (US FDA DailyMed / NCBI StatPearls) are cited for pharmacokinetic or mechanistic parameters, international approvals do not automatically imply CDSCO approval in India.

5. Educational Dosage Context, Formulations & Administration

Educational Dosing & Regimen Summary: 10–20 mg PO Once Daily (Routine 100 mg x 3-day loading dose is now generally OMITTED in clinical practice because it causes high rates of severe diarrhoea and hepatotoxicity!)

Administration & Meal Timing: May be taken with or without food; swallow whole with water | Morning (Once Daily)

6. Pharmacokinetics, Metabolism & Renal/Hepatic Adjustment

Absorption & Disposition:
Absorption, distribution, metabolism, and excretion follow class pharmacokinetic profile; verify patient renal/hepatic function.
Metabolism & Biotransformation:
Renal: Avoid in moderate-to-severe CKD. Hepatic: Contraindicated if baseline ALT >2x ULN; if ALT >3x ULN, STOP Leflunomide and perform Cholestyramine washout!
Elimination & Renal Adjustment:
Renal: Avoid in moderate-to-severe CKD. Hepatic: Contraindicated if baseline ALT >2x ULN; if ALT >3x ULN, STOP Leflunomide and perform Cholestyramine washout!
Hepatic Impairment Considerations:
Renal: Avoid in moderate-to-severe CKD. Hepatic: Contraindicated if baseline ALT >2x ULN; if ALT >3x ULN, STOP Leflunomide and perform Cholestyramine washout!

7. Contraindications, Precautions & High-Risk Warnings

Contraindications & Red-Flag Precautions:
  • ABSOLUTE TERATOGEN & HEPATOTOXICITY BOXED WARNINGS: Strictly contraindicated in pregnancy, women of childbearing potential not using reliable contraception, breastfeeding, pre-existing liver disease (HBV/HCV/cirrhosis or ALT >2x ULN), severe immunodeficiency, bone marrow dysplasia, and severe renal impairment

Key Clinical Precautions: Renal: Avoid in moderate-to-severe CKD. Hepatic: Contraindicated if baseline ALT >2x ULN; if ALT >3x ULN, STOP Leflunomide and perform Cholestyramine washout!

8. Adverse Effects Profile

Common & Mechanism-Related Adverse Effects:
  • Diarrhoea (15–20%), nausea, reversible alopecia (hair thinning — 10%), hypertension (new or worsening BP elevation), mild skin rash, headache
  • Severe/fatal hepatotoxicity (most frequent in first 6 months, especially if combined with Methotrexate!), teratogenicity (congenital malformations), pancytopenia/agranulocytosis, interstitial lung disease (ILD — new dry cough/dyspnoea), peripheral neuropathy, SJS/TEN
Serious / Dose-Limiting Adverse Effects:
  • Monitor for severe hypersensitivity, organ toxicity, or dose-limiting adverse events.

9. Major Drug–Drug, Drug–Food & Drug–Herb Interactions

  • Combined Leflunomide + Methotrexate increases hepatotoxicity and pancytopenia risk (requires monthly LFT/CBC!); inhibits CYP2C9 -> increases Warfarin INR and Phenytoin/Glimepiride levels; Rifampicin increases active teriflunomide peak levels; avoid live vaccines!

10. Clinical Monitoring, Patient Counselling & Storage

Clinical & Laboratory Monitoring: Monitor clinical response, baseline renal/hepatic parameters, and relevant serum biomarkers.

Pharmacist Patient Counselling Points:

  • Patient Counselling Checklist: CRITICAL PREGNANCY & WASHOUT RULE: Leflunomide stays in the body for up to 2 years after stopping! Women must use strict contraception and undergo an 11-day Cholestyramine (8 g TDS) washout protocol before attempting pregnancy; stop alcohol completely and report yellow eyes, fever, or new cough/numbness immediately
  • Meal & Clock Timing Instruction: May be taken with or without food; swallow whole with water (Morning (Once Daily))
  • Missed Dose Protocol: Take same day if remembered; skip if next day
  • Geriatric Dispensing Pearl: Prefer 10 mg OD in older adults; monitor BP, LFTs, and peripheral neuropathy symptoms

Storage, Stability & Dispensing Safeguards: Store below 25°C–30°C in original moisture- and light-resistant packaging out of reach of children. Available forms: Tablets: 10 mg, 20 mg

11. Visual Pharmacology & Mechanism Diagram (svg-v339-01-adme-12-step-journey)

THE 12-STEP ORAL DRUG JOURNEY THROUGH THE HUMAN BODY (LADME) Note: IV bolus enters Step 6 directly (F = 100%); Sublingual & Transdermal routes bypass Step 4–5 Portal First-Pass Metabolism 1. Oral Administration • Tablet / Capsule swallowed • Gastric emptying to duodenum pH 1.5–3.5 (Stomach) 2. Disintegration & Dissolution • Tablet breaks into granules • API dissolves in GI fluid Noyes-Whitney Dissolution Rate 3. GI Epithelial Absorption • Crosses intestinal villi • Passive / Active / P-gp efflux Small Intestine (Large Surface Area) 4. Portal Circulation • Mesenteric veins → Portal vein • Delivers blood to liver sinusoids Pre-systemic Venous Conduit 5. First-Pass Metabolism • Gut & hepatic CYP450 extraction • High: GTN, Propranolol, Morphine Determines Bioavailability (F = f_a × (1-E_H)) 6. Systemic Circulation • Hepatic vein → IVC → Heart • Unbound vs Albumin-bound drug Only FREE drug is active 7–8. Tissue Distribution (Vd) • Capillary permeation to organs • Blood-Brain & Placental barriers Vd = Dose / C_0 (L or L/kg) 9. Target Site of Action • Receptors (GPCR, Ion channel) • Enzymes & Carrier Transporters Pharmacodynamic Effect (E_max, EC50) 10. Hepatic Biotransformation • Phase I (CYP450 Oxidation/Hydrolysis) • Phase II (Glucuronidation/Sulfation) Converts lipophilic drug → hydrophilic metabolite 11. Renal & Biliary Elimination • Nephron: Filtration + Secretion − Reabsorption • Biliary excretion & Enterohepatic recycling Total Clearance CL_tot = CL_renal + CL_hepatic 12. Excretion from the Body • Urine (Primary polar metabolite route) • Bile/Faeces, Expired Air, Sweat, Milk Elimination Half-Life t1/2 = (0.693 × Vd) / CL
svg-v339-01-adme-12-step-journey — 8.1 Complete 12-Step Journey of an Orally Administered Drug (ADME): Figure 8.1: The 12-step physiological journey of a typical orally administered solid dosage form through Liberation, Absorption, Distribution, Metabolism, and Excretion (LADME). Note: Parenteral (IV), sublingual, and inhalational routes bypass gastrointestinal absorption and/or hepatic first-pass metabolism.

12. Authoritative References, Regulatory Sources & Editorial Disclaimer

Primary Compendial & Guideline Reference: Indian Pharmacist Desk Reference — Professional Edition 2.7 (2026–27) • Ch 07 [7.23] (p. 90)

Official Verification Portals: Indian Pharmacopoeia Commission (IPC) & National Formulary of India (NFI) • Central Drugs Standard Control Organization (CDSCO) • Ministry of Health & Family Welfare — NLEM 2022 • NCBI Bookshelf / StatPearls Pharmacology Reference • DailyMed (US FDA Official Prescribing Reference)

Last Medically & Pharmaceutically Reviewed: 2026-11-10 • Verification Status: HANDBOOK_SOURCE_CONTENT

Educational & Clinical Disclaimer: This reference profile is published solely for pharmacy education, academic study, and professional clinical reference. It does not substitute for patient-specific clinical judgement, qualified specialist oncology/medical supervision, or official CDSCO/IP prescribing information. Never self-medicate with prescription, Schedule H/H1/X, NDPS, or oncology medicines.

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Educational Reference Notice: This printout from THE INDIAN PHARMACIST (https://theindianpharmacist.com/medicine/7-23-leflunomide/, Last Reviewed: 2026-11-10) is an educational reference sheet for students and healthcare learners. It is NOT an official prescribing guideline or patient-specific treatment order.