Leishmaniasis Drugs

Leishmaniasis is caused by Leishmania protozoa, transmitted by the bite of infected sandflies. Disease presentation ranges from cutaneous leishmaniasis (skin ulcers at the bite site) to mucocutaneous leishmaniasis (destructive lesions of the nose, mouth, and throat) to visceral leishmaniasis ("kala-azar" -- fever, hepatosplenomegaly, pancytopenia, and weight loss), which is fatal if untreated.

Liposomal amphotericin B is first-line therapy for visceral leishmaniasis in the United States (see the Amphotericin B lesson for its mechanism and adverse effect profile). Other agents used specifically for leishmaniasis include the pentavalent antimonials, miltefosine, and paromomycin.

Sodium stibogluconate (a pentavalent antimonial) is the classic first-line agent in many parts of the world, though its exact mechanism is not fully understood -- it is thought to inhibit parasite glycolysis and fatty acid oxidation. It requires prolonged parenteral (IV or IM) administration and can cause pancreatitis and cardiac conduction abnormalities (QT prolongation).

Miltefosine is the only oral agent approved for leishmaniasis. It disrupts cell membrane lipids and signaling pathways in the parasite. It is significantly teratogenic and requires reliable contraception during and after treatment; GI upset is common.

Paromomycin is an aminoglycoside that inhibits protozoal protein synthesis. It is given topically for cutaneous leishmaniasis or intramuscularly for visceral disease, and carries the aminoglycoside class risks of nephrotoxicity and ototoxicity when given systemically.

Class Drugs

• Sodium Stibogluconate

• Miltefosine

• Paromomycin

Class Mechanism of Action

See individual drugs

Class Applications

Leishmaniasis

• Cutaneous

• Mucocutaneous

• Visceral (kala-azar)

Class Adverse Effects

See individual drugs

Drug Table

Drug Name	Application	Comments	Image
Sodium Stibogluconate	Visceral, cutaneous, and mucocutaneous leishmaniasis	Mechanism; Pentavalent antimonial; Likely inhibits parasite glycolysis and fatty acid oxidation; Adverse Effects; Pancreatitis; QT prolongation/cardiac conduction abnormalities; Requires prolonged parenteral administration	"Sodium" "Stitch" "Glue"
Miltefosine	Visceral, cutaneous, and mucocutaneous leishmaniasis	Only oral agent for leishmaniasis; Mechanism; Disrupts cell membrane lipids and signaling in the parasite; Adverse Effects; Teratogenic -- requires contraception; GI upset (nausea, vomiting, diarrhea)	"Milt" "Foam"
Paromomycin	Cutaneous leishmaniasis (topical); Visceral leishmaniasis (intramuscular)	Mechanism; Aminoglycoside; Inhibits protozoal protein synthesis; Adverse Effects; Nephrotoxicity, ototoxicity (with systemic/IM use)	"Pair" "Om" "Mice"