General Information

Impavido (miltefosine) is an alkyllysophospholipid analogue drug with in vitro activity against the promastigote and amastigote stages of Leishmania species.

Impavido is specifically indicated for adults and adolescents >12 years of age weighing >30 kg (66 lbs) for treatment of: visceral leishmaniasis due to Leishmania donovani, cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis and mucosal leishmaniasis due to Leishmania braziliensis

Impavido is supplied as a capsule for oral administration. The recommended dose is as follows:
weight 30 to 44 kg: one 50 mg capsule twice daily for 28 consecutive days
weight 45 kg or greater: one 50 mg capsule three times daily for 28 consecutive days.
Administer with food to ease or avoid gastrointestinal adverse reactions.
Impavido can cause fetal harm and therefore should not be given to pregnant women.

Mechanism of Action

Impavido (miltefosine) is an alkyllysophospholipid analogue drug with in vitro activity against the promastigote and amastigote stages of Leishmania species. The specific mode of action of miltefosine against Leishmania species is unknown. The mechanism of action of miltefosine 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.

Side Effects

Adverse events associated with the use of Impavido may include, but are not limited to, the following:

• nausea
• vomiting
• diarrhea
• headache
• decreased appetite
• dizziness
• abdominal pain
• pruritus
• somnolence
• elevated transaminases
• elevated creatinine

Clinical Trial Results

The FDA approval of Impavido was based on on a randomized, open-label, active-controlled study, conducted in Bihar, India, an area where L. donovani is known epidemiologically to be the prevalent infecting species. Subjects = 12 years of age with clinical signs and symptoms compatible with visceral leishmaniasis (fever, splenomegaly, and cytopenia) confirmed by the presence of Leishmania amastigotes in aspirates of spleen or bone marrow were randomized to receive oral Impavido or intravenous amphotericin B deoxycholate. Subjects weighing >25 kg received an Impavido 50 mg capsule with meals twice a day. Subjects weighing <25 kg received an Impavido 50 mg capsule with meals once a day in the morning. Amphotericin B was administered intravenously over 6 continuous hours at 1 mg/kg every other day for 15 doses. Impavido was administered to 299 subjects and Amphotericin was administered to 99 subjects. Efficacy was based on final cure, defined as initial cure at end of therapy plus absence of signs and symptoms of visceral leishmaniasis at 6 months follow up. Initial cure at the end of therapy was evaluated by repeat spleen or bone marrow aspiration. Subjects with initial parasitologic cure were followed for 6 months; those without absence of clinical signs and symptoms of visceral leishmaniasis were evaluated with repeat spleen or bone marrow aspiration to determine final cure. Initial cure was achieved in 98% of subjects in each treatment arm. At 6 months after therapy, 88 (29.5%) Impavido recipients and 12 (12.1%) amphotericin B recipients continued to have signs and symptoms suggestive of visceral leishmaniasis. These signs or symptoms were attributed to alternative diagnosis in 73 subjects. The remaining 27 subjects, all in the Impavido arm, underwent evaluation with splenic or bone marrow aspiration, and 9 (3.0%) were positive for Leishmania amastigotes, indicating relapse. The final cure rates for Impavido and amphotericin B were 94% and 97%, respectively.