This document discusses leprostatics, or drugs used to treat leprosy. It describes several common leprostatics including dapsone, clofazimine, rifampin, ethionamide, ofloxacin, and minocycline. For each drug, it covers the mechanism of action, pharmacokinetics, indications, contraindications, adverse reactions, drug interactions, and typical doses. It also provides recommendations for treatment of paucibacillary and multibacillary leprosy depending on drug sensitivity.

1. LEPROSTATICS
dr. Theodorus,MMedSc
Staf Laboratorium Farmakologi
FK UNSRI

2. Leprostatics
 Leprosy (Morbus Hansen) is a chronic infectious disease
caused by M Leprae
 The disease mainly affects the skin, the peripheral
nerves, mucosa of the upper respiratory tract and also
the eye; and the testes
 Leprosy can affect all ages (most often during two
different periode of life: 10-14 and 35-44 years) and both
sexes
 It is estimated that 12 million patients worldwide
 Most often the incubation periode is between 3 to 5
years
 Is transmitted from one untreated person to another via
the respiratory tract or skin

3. 1. DAPSONE (sulfones)
 Dapsone (4,4 diaminodiphenylsulfone,
DDS) is an –analoguie of p-aminobenzoic
acid
 It is white, odorless, crystalline powder
 Insoluble in water and oil
 Inexpensive and relatively non-toxic in the
doses used
 Dapsone is bactericidal as well as
bacteriostatic against M. Leprae

4. dapsone
 MECHANISM OF ACTION
- inhibits the synthesis of folic acid
 PHARMACOKINETICS
- dapsone is rapidly and nearly completely
absorbed from the GI tract
- Peak plasma concentrations are reach-
ed in 1 to 3 hours
- 70-90% of dapsone is plasma protein bound
- Half-life ranges 10 to 50 hours
- Dapsone is acetylated in liver, the rate of acetylation is
genetically determined

5. dapsone
 Pharmacokinetics
- about 70-80% is excreted in urine as
conjugates and metabolites
 INDICATIONS
- Leprosy
- Dermatitis herpetiformis
- Prophylaxis malaria
- Pneumocystis carinii pneumonia
- Treatment of relapsing polychondritis

6. dapsone
 CONTRAINDICATIONS
- Hypersensitivity to dapsone or it’s
derivates
- NADPH
- Liver disease
- Lactation
 ADVERSE REACTIONS
- GI tract: nausea, vomiting, anorexia and
abdominal pain
- Dematologic: drug induced-lupus erythema-
tosus, phototoxicity

7. dapsone
 Adverse reactions
- CNS: peripheral neuropathy, headache,
paresthesia, psychosis
- Hematologic: Dose-related hemolysis
- Liver: Hyperbilirubinemia
- Sulfone syndrome (fever, exfoliative derma-
titis, jaundice and methemoglobinemia) may
develop 5 to 6 weeks after initiation of treat-
ment in malnourished patients

8. dapsone
 DRUG INTERACTION
- Probenicid decreases the urinary excre-
tion of dapsone
- Pyrimethamine may increases hematolo-
gic reaction
- Trimethoprim may increases serum level
of both drugs
 PREPARATION AND DOSES
- Dapsone is available for oral administration in
tablets containing 25 or 100 mg
- Adult: 50 – 100 mg daily

9. 2. CLOFAZIMINE
 Clofazimine is a phenazine dye
 It is a reddish brown powder
 Fat and benzene soluble
 Water insoluble
 Virtually non-toxic
 Clofazimine exerts a slow bactericidal and
also have anti-inflammatory properties
 Investigation: in combination with other
antimycobacterial drugs to treat M.Avium
infection in AIDS patoints

10. clofazimine
 MECHANISM OF ACTION
- The mechanism of the antibactrial action
is uncertain. It preferentially binds to my
- cobacterial DNA and interferes with
growth
- Anti-inflammatory properties have been
suggested , but the mechanism is still poor
-ly understood

11. clofazimine
 PHARMACOKINETICS
- The absorption of this drug is quite varia-
ble, ranging from 45 to 62% after oral
administration
- Highly lipophilic and is deposited predominant-
ly in fatty tissues and in the reticuloendothelial
syatem
- Has a long half –life (70 days) after re-
peated administration
- Slowly excreted, largely unmetabolized, less than 1%
appears in the urine
- Small amount of this drug is eliminated in sputum,
sebum and sweat

12. clofazimine
 INDICATION
- Lepromatous leprosy including dapsone-
resistant lepromatous leprosy and lepro-
matous leprosy complicated by erythema
nodosum leprosum
 CONTRAINDICATION
- There are no known contraindication
 Warning :
- Severe abdominal symptoms (pain or diarrhea)
- Pregnancy women
- Nursing mothers
- Children: safety and efficacy have not been established

13. clofazimine
 ADVERSE REACTIONS
- Pigmentation from pink to brownish-
black (skin)
- Abdominal and gastric pain, hepatitis,
elevated bilirubin and AST
- Taste disorder, dizziness, drowsiness,
diminished vision
- Discoloration of urine, feces, sputum, sweat
- Depression

14. clofazimine
 DRUG INTERACTIONS
- No known
 PREPARATION AND DOSES
- Clofazimine (lamprene) is available for
oral administration in capsules
containing 50 mg and 100 mg
- Dose: 50- 100 mg/daily

15. 3. RIFAMPIN
 A semisynthetic derivative of rifamycin B
 Rifampin is also effective in the treatment
of leprosy (rapid bactericidal)
 To avoid resistance, this drug should be
given in combination with other leprostatics
 The major side effect: hepatotoxicity
 Dapsone concentration may be reduced, but it is
generally considered unnecessary
 Dose: 600 mg/daily or 12-15 mg/kg/daily

16. 4. ETHIONAMIDE
 The use of this drug for the treatment of leprosy
is investigational
 It has been shown to be bactericidal for
M. Leprae, and it’s bactericidal effect is
intermediate between that of dapsone and
rifampin
 It used as alternative for clofazimine (not
acceptable)
 The major side effect: hepatotoxicity
 Dose: 250 – 375 mg/daily

17. 5. OFLOXACIN
 A synthetic fluoroquinolone, acts as a specific
inhibitor of bacterial DNA gyrase and has shown
effective in the treatment of M. Leprae
 Ofloxacin is usually rapidly bactericidal for
susceptible bacteria
 Adverse reaction have affected the
gastrointestinal tract and the central nervous
system most frequently
 Should not be used for patients under 22 years
 Dose: 100-300 mg/daily

18. 6. MINOCYCLINE
 Minocycline is a semisynthetic tetracycline
 It achieves selective concentration in
susceptible organism and induces bacterio
statics by inhibiting protein synthesis
 The most common adverse reaction is
esophagal irritation
 Should not be used in pregnant or nursing
woman or children under 8 years
 Dose: 100 mg, twice daily

19. TREATMENT OF PB LEPROSY
 PB (Paucibacillary) Leprosy: if the number of
basil less than 10 per fields
 For strain sensitive to dapsone
- Dapsone: 100 mg/daily for 6 month, con-
tinued untill skin test result is negative
(3 to 5 years)
- Rifampin: 600 mg/daily for 6 month
 For strain resistance to dapsone
- Clofazimine: 50-100 mg/hari

20. TREATMENT FOR MB LEPROSY
 MB (multibacillary) Leprosy: if the number of
basil more than 10 per fields
 Strain sensitive to dapsone:
- Dapsone: 100 mg/daily for 3 years, some
-times for 10 years (tipe BL and LL)
- Rifampin: 600 mg/daily for 3 years
 Strain resistance to dapsone:
- Clofazimine: 50-100 mg/daily, unlimited
- Rifampin: 600 mg/daily for 3 years