Miltefosine is an oral prescription medication classified as an alkylphosphocholine. Originally investigated in the 1980s as a potential topical treatment for cancer, its purpose shifted when researchers discovered its effectiveness against certain parasitic infections. This discovery established it as an oral treatment for conditions that previously relied on more invasive therapies.
Medical Applications of Miltefosine
The primary use for miltefosine is treating leishmaniasis, a disease caused by Leishmania parasites transmitted through sandfly bites. The drug is effective against the three main forms of the disease. Visceral leishmaniasis is the most severe, affecting internal organs like the spleen and liver. Cutaneous leishmaniasis is the most common and causes skin sores, while mucosal leishmaniasis can destroy mucous membranes in the nose, mouth, and throat. Miltefosine is the only oral drug available for these conditions.
Miltefosine is also a treatment for infections caused by certain free-living amebas, which are rare but often fatal. It is used against Naegleria fowleri, an ameba that causes a devastating brain infection known as primary amebic meningoencephalitis.
The drug is also active against Balamuthia mandrillaris and Acanthamoeba species, which can cause serious infections of the brain, skin, and other body parts. Due to the rarity and severity of these infections, access to miltefosine is often managed through controlled programs. In the United States, the Centers for Disease Control and Prevention (CDC) holds a special protocol for its release.
How Miltefosine Works
Miltefosine’s effectiveness stems from its ability to disrupt the parasite’s cell membrane. As a phospholipid analogue, its structure allows it to integrate into the membrane, interfering with its natural function. This integration disrupts lipid-dependent signaling pathways, which are communications within the cell necessary for the parasite’s survival.
This disruption of the cell membrane’s integrity interferes with key cellular processes and mitochondrial function. This ultimately triggers a form of programmed cell death similar to apoptosis, leading to a breakdown of the parasite’s internal systems and its eventual death.
Administration and Side Effects
Miltefosine is an oral capsule, with the dosage determined by the patient’s body weight and the specific infection being treated. A treatment course lasts for 28 days. It is recommended that the capsules be taken with food to improve tolerance and help manage common side effects.
The most frequently reported side effects are gastrointestinal issues, including nausea, vomiting, and diarrhea. While these are generally manageable, the drug also carries a significant risk of more severe effects. Miltefosine is teratogenic, meaning it can cause severe birth defects if taken during pregnancy.
Miltefosine must not be used by pregnant individuals. Women of childbearing potential are required to use effective contraception during treatment and for five months after the final dose. Patients are also monitored for impacts on kidney and liver function through regular blood and urine tests.