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Drugs Used in Leprosy (Anti-Leprosy Agents) — KDT-Style for 2nd Year MBBS

Classification of Anti-Leprosy Drugs

1. Primary (First-Line) Drugs — WHO MDT Regimen

2. Secondary (Reserve/Alternative) Drugs

• Ofloxacin (fluoroquinolone)
• Minocycline (tetracycline)
• Clarithromycin (macrolide)

3. Drugs for Leprosy Reactions

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WHO Multidrug Therapy (MDT) Regimens

Paucibacillary (PB) Leprosy

• Duration: 6 months (6 blister packs)
• Follow-up: 2 years of monitoring after completion

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Multibacillary (MB) Leprosy

• Duration: 12 months (12 blister packs)
• Follow-up: At least 2 years after treatment
• Cure rate: ~99%

Note (2018 WHO update): WHO suggested adding clofazimine to PB-MDT as well, but this is not yet universally implemented due to risk of skin discoloration affecting compliance. — Harrison's Principles of Internal Medicine 22E, 2025

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Individual Drug Profiles

1. Dapsone (DDS — Diaminodiphenyl Sulfone)

• Mechanism: PABA antagonism → inhibits folate synthesis → weakly bactericidal
• Half-life: ~28 hours (long)
• Dose: 100 mg/day (adult), 50 mg/day (children 10–14 yr)
• Adverse effects:
  • Mild hemolysis (dose-dependent) → anemia
  • Methemoglobinemia (especially in G6PD deficiency)
  • DDS Syndrome / Dapsone Hypersensitivity Syndrome: Fever + skin rash + eosinophilia + lymphadenopathy + hepatitis ± encephalopathy; onset ~6 weeks after starting therapy; fatality 10% (death from liver failure/sepsis/bone marrow failure)
  • Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)
  • Agranulocytosis, cholestatic jaundice (rare)

2. Rifampicin

• Mechanism: Inhibits DNA-dependent RNA polymerase → blocks RNA synthesis → most bactericidal anti-leprosy drug
• Dose: 600 mg once monthly (supervised)
• Adverse effects:
  • Orange-red discoloration of urine, tears, sweat
  • Flulike syndrome (with intermittent dosing) — fever, myalgia, asthenia
  • Hepatotoxicity, nausea/vomiting
  • Purpura, epistaxis

3. Clofazimine

• Mechanism: Unknown; likely binds mycobacterial DNA; also has anti-inflammatory properties (useful in leprosy reactions)
• Dose: 300 mg once monthly (supervised) + 50 mg/day (self-administered) — MB only
• Key adverse effects:
  • Skin hyperpigmentation — red to purple/black discoloration, especially in lesions; fades in 6–12 months after stopping (traces may persist up to 4 years)
  • Ichthyosis of shins and forearms
  • GI effects — cramps, diarrhea, weight loss (crystal deposition in small bowel wall)
  • Pink discoloration of urine, sputum, sweat
• Note: Fat-soluble dye; accumulates in fat, macrophages, mesenteric lymph nodes

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Treatment of Leprosy Reactions

Type 1 — Reversal Reaction (Delayed Hypersensitivity to M. leprae antigens)

• More common in borderline types
• Features: Edema, erythema of existing lesions, acute neuritis
• Treatment: Prednisolone 1–2 mg/kg/day, tapered by 10–15% every 15 days over ~3 months; calcium + Vitamin D supplementation during steroid use

Type 2 — Erythema Nodosum Leprosum (ENL — Immune Complex/Arthus reaction)

• Seen in lepromatous leprosy; triggered by antigen release during therapy
• Features: Raised tender subcutaneous nodules, fever, constitutional symptoms, orchitis, iritis
• Treatment:
  • Thalidomide 100–400 mg/day — drug of choice (teratogenic — mandatory pregnancy testing + contraception in women of childbearing age)
  • Clofazimine — also useful for ENL
  • Prednisolone — for associated nerve damage

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Quick Recall Table (Exam Format)

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Sources: Harrison's Principles of Internal Medicine 22E (2025), Goodman & Gilman's Pharmacological Basis of Therapeutics, Fitzpatrick's Dermatology — consistent with WHO MDT guidelines referenced in KD Tripathi's Essentials of Medical Pharmacology.

• Rifampicin is always given monthly and supervised
• Dapsone is given daily (self-administered)
• Clofazimine is added only in MB leprosy (currently)
• Thalidomide = drug of choice for ENL (Type 2 reaction)
• DDS Syndrome occurs ~6 weeks after starting dapsone