1662. Pushing the Dose: Miltefosine Treatment for a Supersized American with Cutaneous Leishmaniasis

BACKGROUND: Miltefosine (Profounda, FL) is an oral alkylphospholipid drug which is approved by the Food and Drug Administration for the treatment of some species of New World cutaneous leishmaniasis. The maximal daily recommended dosage is 50 mg t.i.d for 28 days; yet there is some evidence that doses <2.5 mg/kg/day may be associated with lesser efficacy. We treated a healthy 30-year-old, 117 kg, 78 inches (low body fat) male with cutaneous Leishmania tropica infection with miltefosine after multiple unsuccessful treatment regimens. This presentation will provide the background considerations and the outcome of our approach of using higher daily dosages of miltefosine. METHODS: We used a miltefosine dose escalation of 50 mg t.i.d (1.28 mg/kg/day) for days 1–5 with fatty food, increasing to 50 mg. q.i.d. (1.71 mg/kg/day) for days 6–15. For days 16–28, the patient received 250 mg daily (2.13 mg/kg/day). Weekly blood testing was done for complete blood count, metabolic panel, and miltefosine pharmacokinetics. Plasma concentrations were assayed using a validated liquid chromatography coupled to tandem mass spectrometry methodology. RESULTS: The patient experienced a good clinical result with his two ulcerative lesions on the left leg healing with full epithelialization by day 28. He tolerated miltefosine well until he escalated to 250 mg daily when he noted 2 hours of fatigue and dizziness after the dose, nausea and after the fourth day he developed epididymitis. His serum creatinine was elevated (1.4 mg/dL). The epididymitis resolved after approximately a week, his other symptoms resolved soon after completing the day 28 dose. Serial miltefosine plasma levels accumulated during treatment to 30, 34, 44, and 53 μg/mL on days 7, 14, 21, and 27 after the start of treatment (dropping to 27 μg/mL 8 days post), with an apparent distribution half-life of 7 days. CONCLUSION: Miltefosine yielded healing of recalcitrant L. tropica infection but was associated with adverse effects at the 250 mg daily dose that severely limited the activity of the patient for the final 8 days of therapy; however, they were not dose-limiting. Miltefosine accumulation appeared to be dose-proportional compared with reported concentrations with a median 1.8 mg/kg/day dose in Dutch cutaneous leishmaniasis patients (median weight 85 kg). DISCLOSURES: All authors: No reported disclosures.