Miltefosine is an oral anti-infective and one of the medicines with established efficacy in the treatment of some forms of leishmaniasis, a parasitic infection spread by sandflies. Leishmaniasis can take different forms, including cutaneous leishmaniasis, mucocutaneous leishmaniasis, and visceral leishmaniasis (VL).
Post-Kala-Azar Dermal Leishmaniasis (PKDL) is a sequela which generally occurs 6 months to several years after apparent cure of VL. Although uncommon, leishmanial ocular infections have been reported, and keratitis and uveitis can also occur with the disease.
There have been reports of ocular disorders, sometimes serious, in patients treated with miltefosine for PKDL (and exceptionally for VL). Reports of ocular disorders have originated mostly from India, where miltefosine has been used in VL patients for 28 days, and for 12 weeks in PKDL. Ocular disorders include rare cases of unilateral and bilateral blindness, permanent in some cases, ulcerative keratitis, leukocoria, blurred vision, ocular hyperaemia, photophobia and eye pain. In several cases, as reported, symptoms resolved following discontinuation of the treatment.
The issue was discussed by the WHO Advisory Committee on Safety of Medicinal Products (ACSoMP) and a group of pharmacovigilance experts was formed to further review this safety signal. WHO is also working closely with relevant stakeholders in India to further investigate this issue.
At this stage, the available data is insufficient to confirm or rule out a causal association with miltefosine. However, in view of the seriousness of some reports, the WHO recommends in the interim that healthcare professionals:
- take note of ocular conditions at the time of diagnosis of PKDL or other clinical forms (visceral, cutaneous and/or mucocutaneous) of leishmaniasis requiring miltefosine treatment in monotherapy or in combination with other antileishmanial medicines;
- inform patients about the disease, duration of treatment and potential risks of ocular disorders , and advise them to immediately contact a healthcare professional if any ocular disorders occur;
- perform ocular examinations on regular intervals during the treatment;
- consider cessation of treatment with miltefosine if ocular disorders occur and consult an ophthalmologist for further investigation and management;
- report any ocular adverse events to their national pharmacovigilance centre.
Patients should contact their healthcare professional if they have questions or concerns.
WHO will update this information as more data becomes available.
