DRUGS USED IN LEPROSY
Mycobacterium leprae has never been grown in vitro, but animalmodels, such as growth in injected mouse footpads, have permit-ted laboratory evaluation of drugs. Only those drugs with the widest clinical use are presented here. Because of increasing reports of dapsone resistance, treatment of leprosy with combinations of the drugs listed below is recommended.
Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to pre-vent and treat Pneumocystis jiroveci pneumonia in AIDS patient
Sulfones are well absorbed from the gut and widely distributed throughout body fluids and tissues. Dapsone’s half-life is 1–2 days, and drug tends to be retained in skin, muscle, liver, and kidney. Skin heavily infected with M leprae may contain several times more drug than normal skin. Sulfones are excreted into bile and reab-sorbed in the intestine. Excretion into urine is variable, and most excreted drug is acetylated. In renal failure, the dose may have to be adjusted. The usual adult dosage in leprosy is 100 mg daily. For children, the dose is proportionately less, depending on weight.
Dapsone is usually well tolerated. Many patients develop some hemolysis, particularly if they have glucose-6-phosphate dehydro-genase deficiency. Methemoglobinemia is common, but usually is not a problem clinically. Gastrointestinal intolerance, fever, pruri-tus, and various rashes occur. During dapsone therapy of leproma-tous leprosy, erythema nodosum leprosum often develops. It is sometimes difficult to distinguish reactions to dapsone from manifestations of the underlying illness. Erythema nodosum lep-rosum may be suppressed by corticosteroids or by thalidomide.
Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in lepromatous leprosy. Because of the probable risk of emergence of rifampin-resistant M leprae, the drug is given in com-bination with dapsone or another antileprosy drug. A single monthly dose of 600 mg may be beneficial in combination therapy.
Clofazimine is a phenazine dye that can be used as an alternative to dapsone. Its mechanism of action is unknown but may involve DNA binding.
Absorption of clofazimine from the gut is variable, and a major portion of the drug is excreted in feces. Clofazimine is stored widely in reticuloendothelial tissues and skin, and its crystals can be seen inside phagocytic reticuloendothelial cells. It is slowly released from these deposits, so that the serum half-life may be 2 months.
Clofazimine is given for sulfone-resistant leprosy or when patients are intolerant to sulfones. A common dosage is 100 mg/d orally. The most prominent untoward effect is skin discoloration ranging from red-brown to nearly black. Gastrointestinal intoler-ance occurs occasionally.