“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Wednesday, August 6, 2025

Leprostatics


Definition and Purpose

Leprostatics are a pharmacological class of antimicrobial agents specifically used for the treatment of leprosy (Hansen’s disease), a chronic infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. These drugs act by inhibiting the growth or killing the causative mycobacteria. Treatment with leprostatics is essential not only for curing the disease but also for halting transmission, minimizing disability, and preventing relapse.

Core Characteristics of Leprostatics

  • Antimycobacterial activity: Most leprostatics work by interfering with essential metabolic pathways of M. leprae.

  • Combination therapy: To prevent drug resistance, these agents are typically administered as part of a multidrug therapy (MDT) regimen.

  • Long duration of therapy: Due to the slow-growing nature of M. leprae, treatment spans several months to years.

  • Bactericidal or bacteriostatic: Depending on the drug, it can kill the bacteria or merely inhibit its replication.

  • Immunomodulatory role: Some agents, like clofazimine, also exhibit anti-inflammatory properties useful in managing leprosy reactions.

List of Common Leprostatic Drugs

Below are the primary leprostatic agents approved and recommended for use:

1. Dapsone

  • Mechanism of Action: Inhibits dihydropteroate synthase, interfering with folate synthesis in bacteria.

  • Therapeutic Role: Bacteriostatic against M. leprae. Core component of MDT.

  • Dosage: Typically 100 mg orally once daily in adults.

  • Notable Side Effects: Hemolysis (especially in G6PD deficiency), methemoglobinemia, hypersensitivity syndrome, peripheral neuropathy.

2. Rifampicin (Rifampin)

  • Mechanism of Action: Binds to the β-subunit of bacterial RNA polymerase, inhibiting transcription.

  • Therapeutic Role: Bactericidal against M. leprae. The most potent leprostatic drug.

  • Dosage: 600 mg once monthly (supervised dose).

  • Notable Side Effects: Hepatotoxicity, orange discoloration of body fluids, drug interactions (CYP450 inducer).

3. Clofazimine

  • Mechanism of Action: Binds bacterial DNA, leading to growth inhibition; also has anti-inflammatory activity.

  • Therapeutic Role: Bacteriostatic; useful in controlling erythema nodosum leprosum (ENL).

  • Dosage: 50 mg daily + 300 mg monthly (supervised).

  • Notable Side Effects: Skin discoloration (reddish-brown), gastrointestinal distress, ichthyosis.

4. Minocycline

  • Mechanism of Action: Inhibits bacterial protein synthesis via the 30S ribosomal subunit.

  • Therapeutic Role: Used in cases resistant to first-line drugs.

  • Dosage: Typically 100 mg daily.

  • Notable Side Effects: Vestibular toxicity, pigmentation, hypersensitivity.

5. Ofloxacin

  • Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV.

  • Therapeutic Role: Effective against rifampin-resistant M. leprae strains.

  • Dosage: 400 mg daily or 800 mg as monthly pulse.

  • Notable Side Effects: Tendinopathy, QT prolongation, CNS effects.

6. Moxifloxacin

  • Mechanism of Action: Fluoroquinolone similar to ofloxacin.

  • Therapeutic Role: Used in MDT in resistant leprosy.

  • Notable Side Effects: Same as ofloxacin, with a higher risk of QT prolongation.

7. Clarithromycin

  • Mechanism of Action: Macrolide that inhibits bacterial protein synthesis via the 50S ribosomal subunit.

  • Therapeutic Role: Alternative in patients intolerant to other agents.

  • Dosage: 500 mg daily.

  • Notable Side Effects: Gastrointestinal disturbances, hepatotoxicity, QT prolongation.

Standard Treatment Regimens (WHO Guidelines)

Multibacillary (MB) Leprosy

  • Drugs: Rifampicin, Dapsone, Clofazimine

  • Duration: 12 months

  • Doses:

    • Rifampicin 600 mg monthly

    • Clofazimine 300 mg monthly + 50 mg daily

    • Dapsone 100 mg daily

Paucibacillary (PB) Leprosy

  • Drugs: Rifampicin, Dapsone

  • Duration: 6 months

  • Doses:

    • Rifampicin 600 mg monthly

    • Dapsone 100 mg daily

Single Lesion Leprosy

  • ROM Regimen (single dose):

    • Rifampicin 600 mg

    • Ofloxacin 400 mg

    • Minocycline 100 mg

Mechanisms of Action Summary

  • Dapsone: Competitive inhibitor of folate pathway enzyme → bacteriostatic

  • Rifampicin: RNA synthesis inhibition → bactericidal

  • Clofazimine: DNA binding + anti-inflammatory → bacteriostatic and symptom control

  • Minocycline/Clarithromycin: Protein synthesis inhibition → variable activity

  • Ofloxacin/Moxifloxacin: DNA synthesis inhibition → potent bactericidal

Side Effects and Monitoring

DrugMajor Side EffectsMonitoring Requirements
DapsoneHemolysis, rash, neuropathyCBC, G6PD status
RifampicinHepatotoxicity, drug interactionsLFTs
ClofazimineSkin pigmentation, GI upsetSkin monitoring
OfloxacinTendon rupture, CNS issuesECG (QT), tendon monitoring
ClarithromycinQT prolongation, GI symptomsECG, LFTs



Contraindications and Cautions

  • Dapsone: Contraindicated in G6PD deficiency due to hemolysis risk.

  • Rifampicin: Avoid in hepatic impairment, potent inducer of CYP450.

  • Clofazimine: Use caution in patients concerned with skin discoloration.

  • Ofloxacin/Moxifloxacin: Avoid in patients with seizure disorders or arrhythmias.

  • Clarithromycin: Avoid in QT prolongation, caution with other CYP3A4 substrates.

Drug Interactions

  • Rifampicin: Strong inducer of CYP3A4, reduces efficacy of oral contraceptives, warfarin, antiretrovirals.

  • Dapsone: May interact with folate antagonists (e.g., trimethoprim).

  • Clofazimine: Limited interactions but may delay the absorption of other oral drugs.

  • Fluoroquinolones (Ofloxacin/Moxifloxacin): Interaction with antacids, QT-prolonging agents.

  • Clarithromycin: Inhibits CYP3A4; increases levels of drugs like theophylline, carbamazepine.

Special Populations

Pregnancy

  • Dapsone and Clofazimine are generally considered safe with caution.

  • Rifampicin is used with caution; vitamin K supplementation recommended due to bleeding risk in newborns.

  • Ofloxacin and Moxifloxacin are generally avoided due to cartilage toxicity.

  • Clarithromycin is typically avoided unless no alternatives are available.

Breastfeeding

  • Dapsone and Rifampicin are excreted in breast milk; monitor for signs of hemolysis in infants.

  • Clofazimine also enters breast milk and may cause skin discoloration in the infant.

Children

  • WHO MDT regimens are adjusted based on weight.

  • Clofazimine and Rifampicin are well tolerated; Dapsone needs close hemolysis monitoring.

Resistance and Alternative Therapies

  • Resistance to dapsone and rifampicin has been documented, especially in relapsed or previously treated cases.

  • WHO recommends resistance surveillance using PCR-based testing.

  • In resistant cases, second-line agents such as minocycline, clarithromycin, and fluoroquinolones are used in combination regimens.

Prophylactic Use

  • Post-exposure prophylaxis (PEP) with a single dose of rifampicin is recommended for contacts of newly diagnosed patients.

  • WHO promotes contact tracing and prophylaxis as part of its global leprosy strategy to reduce transmission.

Recent Advances and Research

  • Development of shorter-course regimens and new biomarkers for disease activity and drug resistance.

  • Ongoing studies evaluating bedaquiline, linezolid, and delamanid (used in TB) for M. leprae.

  • Advances in genomic surveillance to monitor resistance mutations (e.g., rpoB, folP1).

Storage and Stability

  • Dapsone: Store at room temperature, away from light and moisture.

  • Rifampicin: Sensitive to moisture and heat; store in a tightly closed container.

  • Clofazimine: Protect from light; store at room temperature.

  • Fluoroquinolones: Avoid storing in extreme heat or direct light.

  • Clarithromycin: Store in a dry place below 25°C.

Global Guidelines and Programs

  • WHO provides free MDT blister packs worldwide.

  • National Leprosy Eradication Programmes (NLEP) are active in endemic countries such as India, Brazil, Indonesia.

  • MDT coverage, early detection, and stigma reduction are global priorities.

Brand Names and Formulations

  • Dapsone: Avlosulfon, DDS

  • Rifampicin: Rifadin, Rimactane

  • Clofazimine: Lamprene

  • Ofloxacin: Tarivid

  • Minocycline: Minocin

  • Clarithromycin: Biaxin

Key Points for Clinical Practice

  • Always initiate MDT to prevent resistance.

  • Monitor adverse reactions and liver function periodically.

  • Counsel patients on long duration and adherence.

  • Address psychosocial concerns such as stigma and disability.

  • Promptly manage lepra reactions (Type I and II) with corticosteroids or thalidomide (in ENL).



on

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)