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, particularly if low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy of lepromatous leprosy. A combination of dapsone plus rifampin is commonly used for leprosy with a lower organism burden. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients.
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 reabsorbed 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 dehydrogenase deficiency. Methemoglobinemia is common but usually is not clinically significant. Gastrointestinal intolerance, fever, pruritus, and rash occur. During dapsone therapy of lepromatous leprosy, erythema nodosum leprosum often develops. It is sometimes difficult to distinguish reactions to dapsone from manifestations of the underlying illness. Erythema nodosum leprosum may be suppressed by thalidomide (see Chapter 55).
Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in leprosy and is given with at least one other drug to prevent emergence of resistance. Even a dose of 600 mg per month may be beneficial in combination therapy.
Clofazimine is a phenazine dye used in the treatment of multi-bacillary leprosy, which is defined as having a positive smear from any site of infection. Its mechanism of action has not been clearly established. 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 the serum half-life may be 2 months. A common dosage of clofazimine is 100–200 mg/d orally. The most prominent adverse effect is discoloration of the skin and conjunctivae. Gastrointestinal side effects are common. This medication is no longer commercially available, but it can be obtained through established programs. For example, an investigational new drug (IND) program is established in the USA through the National Hansen’s Disease Program. Internationally, ministries of health can make requests directly to the World Health Organization.
rapidly emerges when used as a single drug in the treatment of active infection
First-line agent for tuberculosis • nontuberculous mycobacterial infections • eradication of meningococcal colonization, staphylococcal infections •RifampinInhibits DNA-dependent RNA polymerase, thereby blocking production of RNA •Rifabutin: Oral; similar to rifampin but less cytochrome P450 induction and fewer drug interactions •Rifapentine: Oral; long-acting analog of rifampin that may be given once weekly in select cases during the continuation phase of tuberculosis treatment or for treatment