Which medications in the drug class Antileishmaniasis Agents are used in the treatment of Leishmaniasis?

Updated: Feb 18, 2020
  • Author: Craig G Stark, MD, FACP, FFTM, RCPS(Glasg), FISTM; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Answer

Antileishmaniasis Agents

Miltefosine is a new oral drug that is now approved in the United States to treat cutaneous, mucocutaneous, and visceral disease from specific Leishmania species. The antiprotozoal effect is poorly understood.

Sodium stibogluconate is a compound available in English-speaking countries, and meglumine antimonate is a compound available in Latin American countries.

Sodium stibogluconate (Pentostam)

Sodium stibogluconate has been the drug of choice for the treatment of cutaneous and mucocutaneous leishmaniasis in the United States. This agent is also effective against visceral leishmaniasis and is often the first-line treatment outside the United States. Patients with long-standing disease may require long-term therapy. Although not FDA approved, sodium stibogluconate is currently available from the Centers for Disease Control and Prevention (CDC) as an investigational new drug (404-639-3670).

Sodium stibogluconate acts by interfering with the metabolism of the parasite. This agent may be administered intravenously (IV) or intramuscularly (IM), with similar pharmacokinetic parameters. IV use is preferred, because large volumes are required. Sodium stibogluconate is available only from the CDC at 100 mg/mL. Dilute each mL in 10 mL of 5% dextrose water, and administer it over 15 minutes to prevent thrombophlebitis.

This agent can be administered at recommended dose for 30 days without toxicity. Children often tolerate adverse effects better than adults and may not require electrocardiographic (ECG) monitoring.

Primary unresponsiveness ranges from 2-8%. The relapse rate is usually below 10%, but it has been reported to be as high as 30% in Kenya. An increasing incidence of resistance is reported in India.

Miltefosine (Impavido)

Miltefosine is an alkylphosphocholine that was originally developed as an antineoplastic agent. The specific mode of action against Leishmania species is unknown but is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome C oxidase (mitochondrial function), and apoptosis-like cell death.

In March 2014, the FDA approved miltefosine for visceral leishmaniasis caused by L donovani; cutaneous leishmaniasis due to L braziliensis, L guyanensis, and L panamensis; and mucosal leishmaniasis due to L braziliensis. FDA approval was for patients aged 12 years or older, those who weigh at least 66 lb, and those who aren't pregnant or breastfeeding.

Since 2002, this agent has rapidly become the drug of choice for visceral leishmaniasis in India. A short-course regimen consisting of a single dose of liposomal amphotericin followed by 7-14 days of miltefosine has resulted in cure rates greater than 90% in north India. Miltefosine is registered in India and Europe for the treatment of visceral leishmaniasis.

Its mechanism of action is likely due to inhibition of phospholipid and sterol biosynthesis via interference with cell signal transduction pathways. Resistance against miltefosine has been found.


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