Most Hansen's disease patients today are treated with
- Rifampin and
- Clofazimine (in multibacillary cases)
Alternate medications, including ofloxacin and other fluoroquinolones, minocycline and clarithromycin, are also being used in select cases or drug trials.
In the past streptomycin, ethionamide, prothionamide, thiambutosine and thiacetazone were occasionally used. Their toxicity, limited effectiveness, and requirement for intramuscular administration have effectively eliminated them from consideration for therapy today.
Dapsone, rifampin, clofazimine, clarithromycin, ofloxacin and levofloxacin are Food and Drug Administration category C (risk cannot be ruled out for use in pregnancy).
Minocycline, however, is category D (positive evidence of risk exists for use in pregnancy). The use of dapsone, clofazimine and rifampin in treatment regimens throughout the world since the mid-1980's, however, suggests that they are probably safe in pregnancy.
Dapsone is inexpensive and relatively non-toxic in the doses used, although rare cases of the dapsone syndrome or agranulocytosis are reported. A shortened red cell survival is common with the drug, but severe hemolytic anemias are uncommon except in those with a severe glucose-6-phosphate- dehydrogenase deficiency. A dose of 100 mg daily is weakly bactericidal against M. leprae and such a dose exceeds the Minimum Inhibitory Concentration by a factor of about 500. Such doses will even inhibit the multiplication of M. leprae mutants with low tomoderate degrees of dapsone resistance. The maximum dosage should be used from the start and should not be reduced during lepra reactions.
Rifampin is the most bactericidal drug available for the treatment of HD. The standard U.S. dose is 600 mg daily, but even a single dose of 600 mg monthly as used in the World Health Organization regimens is highly bactericidal. Toxicity of the drug is relatively low but is related to the size of the dose and the interval between doses. The standard use for leprosy has proven relatively non-toxic despite occasional cases of liver dysfunction, renal failure, bone marrow suppression and “flu like” syndrome. Daily administration of rifampin has major effects on activity of the the liver cytochrome 3A4, and greatly affects other medications such as oral contraceptives, corticosteroids and HIV protease inhibitors.
In the standard dose of 50 mg daily clofazimine is virtually non-toxic. Pigmentation of the skin, particularly within skin lesions, is common, but it clears completely after treatment is discontinued. The higher doses of clofazimine are sometimes used for control of reactions, and may produce severe gastrointestinal side effects. Clofazimine is weakly bactericidal against M. leprae, but when given with dapsone the combination is much more bactericidal than either drug alone.
Although a large number of fluoroquinolones have been developed, some such as ciprofloxacin are not active against M. leprae. Of those which are active, most interest has centered on ofloxacin in a dose of 400 mg daily or in various investigational intermittent regimens. Like all fluoroquinolones, ofloxacin acts by interfering with bacterial DNA replication by inhibiting the A subunit of the enzyme DNA-gyrase. A single 400 mg dose demonstrates bactericidal activity although less than that demonstrated by a single dose of rifampin. Twenty-two doses have been found to be capable of killing 99.99 percent of viable M. leprae. Side-effects include nausea, diarrhea and other gastrointestinal complaints, and a variety of central nervous system complaints including insomnia, headaches, dizziness, nervousness and hallucinations. Serious problems are infrequent and only occasionally require discontinuing the drug. Levofloxacin, the active L-racemer of ofloxacin, has replaced ofloxacin in many U.S. formularies, but is not officially included in WHO recommendations. The World Health Organization (WHO) has included ofloxacin as a component of ROM therapy (Rifampin-Ofloxacin-Minocycline).
Recently the World Health Organization (WHO) recommended a simplified and convenient regimen called ROM (Rifampin 600 mg-Ofloxacin 400 mg-Minocycline 100 mg) which is given as a directly observed therapy. ROM has been officially recommended by WHO as a one-time dose for single lesion paucibacillary disease. An unofficial regimen for multibacillary disease, consisting of 24 doses of once-monthly ROM, is also given by WHO on their Web site.
This is the only member of the tetracycline group of antibiotics which demonstrates significant activity against M. leprae. This may be because of its lipophilic properties which allow it to penetrate cell walls. The standard dose is 100 mg daily. It is bactericidal for M. leprae to a somewhat greater degree than clarithromycin but much less so than rifampin. It was very effective clinically when tried as monotherapy in eight patients, but two months therapy was required before all footpad inoculations became negative.
Like the other tetracyclines it inhibits protein synthesis via a reversible binding at the 30S ribosomal subunit, thereby blocking the binding of aminoacyl-transfer RNA to the messenger RNA ribosomal complex. Side effects include discoloration of infant's or children's teeth, occasional pigmentation of the skin and mucous membranes, various gastrointestinal complaints and central nervous system toxicity including dizziness and unsteadiness. Its frequent prolonged use for the treatment of acne, however, indicates that in general it is relatively non-toxic.
Several members of this group including erythromycin have been evaluated. Clarithromycin shows significant promise at this time. The drug has potent bactericidal activity but it is clearly less bactericidal than rifampin. At a dose of 500 mg Macrolides (Clarithromycin) daily in Hansen's Disease (HD) patients, 99% of HD bacilli are killed in 28 days and 99.9% by 58 days.
The drug acts by inhibition of bacterial protein synthesis by linking to the 50S ribosomal subunit thereby preventing elongation of the protein chain. As a group, the macrolides are relatively non-toxic. Gastrointestinal irritation, nausea, vomiting and diarrhea are the most common problems but they usually do not necessitate discontinuation of the drug.