Before discussing FDA-approved treatments for leishmaniasis, it is important to remember that information provided here is for general knowledge only and should not be taken as medical advice. Always consult with a healthcare provider for any health concerns or before starting any new treatment.
The treatment of leishmaniasis depends heavily on the specific form of the disease—visceral (affecting internal organs), cutaneous (skin), or mucosal (nose and mouth). For infections acquired in the United States or managed under FDA guidelines, two primary systemic medications are approved: miltefosine and liposomal amphotericin B. The Centers for Disease Control and Prevention (CDC) provides guidance on their use, which is critical for clinicians in navigating the complexities of this parasitic infection.
Oral Miltefosine (Impavido®)
Miltefosine is a major advancement in leishmaniasis treatment because it is the only oral medication approved by the FDA for all three primary forms of the disease. This oral route is a significant advantage, particularly in settings with limited healthcare infrastructure, and it enhances patient compliance.
FDA-approved indications
In 2014, the FDA approved oral miltefosine (Impavido®) for the treatment of:
- Visceral leishmaniasis (VL): Specifically caused by Leishmania donovani.
- Cutaneous leishmaniasis (CL): Caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis.
- Mucosal leishmaniasis (ML): Caused by Leishmania braziliensis.
This approval is for adults and adolescents aged 12 years and older, who weigh at least 30 kg (66 lbs). Use for other species or younger children is considered off-label.
Administration
The administration of oral miltefosine typically involves taking the medication for a specific duration as prescribed by a healthcare professional. It is generally recommended to take the medication with food to help reduce potential gastrointestinal side effects. The specific amount of medication and the frequency of administration are determined by the prescribing physician based on individual factors.
Safety considerations and limitations
Miltefosine has important safety considerations. It is teratogenic, meaning it can cause birth defects. Therefore, it is contraindicated in pregnant women, and females of reproductive potential must use effective contraception during treatment and for five months afterward. Common adverse effects include gastrointestinal distress (nausea, vomiting), lack of appetite, and mild, reversible kidney and liver function abnormalities.
Intravenous Liposomal Amphotericin B (AmBisome®)
Liposomal amphotericin B (AmBisome®) is an FDA-approved intravenous (IV) treatment, but its approval is limited to a single form of the disease.
FDA-approved indications
- Visceral leishmaniasis (VL): Liposomal amphotericin B is FDA-approved for the treatment of visceral leishmaniasis in both immunocompetent and immunocompromised patients. It is often the drug of choice for VL, especially in antimony-resistant infections.
Advantages over conventional amphotericin B
The liposomal formulation represents a significant improvement over the older conventional amphotericin B deoxycholate. Encapsulating the drug in liposomes reduces its toxicity, particularly nephrotoxicity, and minimizes adverse infusion-related reactions.
Administration
Liposomal amphotericin B is administered intravenously. The specific amount given and the duration of treatment depend on the patient's immune status and the severity of the infection, and is determined by a healthcare provider. The course of treatment typically involves a series of infusions given over a period of time.
Other treatments and considerations
While miltefosine and liposomal amphotericin B are the two FDA-approved systemic treatments available in the U.S., other medications are used globally or under special protocols. For example, pentavalent antimonials (sodium stibogluconate) are traditional mainstays in many endemic areas but are not FDA-approved in the U.S. and carry greater toxicity and resistance risks. Topical therapies with agents like paromomycin can be used for localized cutaneous lesions, sometimes via compounded formulations.
The selection of a treatment regimen is a nuanced decision, influenced by the specific infecting Leishmania species, the clinical form of the disease, the geographic area of acquisition, and the patient's overall health. Miltefosine is effective against specific species, and its efficacy can vary by region. Liposomal amphotericin B, while broader in its VL coverage, is not indicated for CL or ML based on FDA approval.
Conclusion
In summary, the FDA-approved options for treating leishmaniasis in the United States include the oral agent miltefosine (Impavido®) and the intravenous liposomal amphotericin B (AmBisome®). Miltefosine is a versatile option, approved for specific forms of cutaneous, mucosal, and visceral leishmaniasis. Liposomal amphotericin B, while only approved for visceral leishmaniasis, offers a valuable, less toxic alternative to older formulations. The final treatment choice must be carefully individualized by a healthcare provider, considering the infecting species, disease manifestation, patient factors, and potential for side effects. For detailed guidance on clinical management, healthcare providers can consult resources like the CDC guidelines on leishmaniasis.
Comparison of FDA-Approved Leishmaniasis Treatments
| Feature | Miltefosine (Impavido®) | Liposomal Amphotericin B (AmBisome®) |
|---|---|---|
| Route of Administration | Oral (capsule) | Intravenous (IV) infusion |
| FDA-Approved For | Specific forms of cutaneous, mucosal, and visceral leishmaniasis. | Visceral leishmaniasis only. |
| Advantages | Convenient oral administration, at-home treatment possible, effective against multiple forms and species. | Generally lower toxicity than conventional amphotericin B, shorter course than older treatments, effective against antimony-resistant strains. |
| Key Limitations | Teratogenic (requires pregnancy precautions), common gastrointestinal side effects (nausea, vomiting), resistance emerging. | Requires hospitalization and IV administration, high cost can be a barrier to access in developing regions, not approved for cutaneous or mucosal forms. |
| Patient Population | Adults and adolescents ($\geq 12$ years and $\geq 30$ kg). | Adults and children with VL; administration plan depends on immune status. |
