Introduction Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and pentamidine. Although these drugs have been used for decades, there is still no systematic review about their safety. The objective of this review was to identify the adverse effects associated with these drugs and to estimate the frequency of these effects.

Methods Intervention studies, case series and case reports containing information regarding clinical, laboratory or electrocardiographic adverse effects of drugs used for the treatment of cutaneous leishmaniasis were systematically retrieved from 10 databases searched between 13 August 2008 and 31 March 2009.

Results The 65 studies included in this review had treated 4359 patients from 12 countries infected with 8 different Leishmania species. Despite the small number of drugs used in these studies, a wide variability in the therapeutic regimens was observed. As a consequence, the adverse effects of these drugs needed to be classified jointly according to system, irrespective of daily dose, duration of treatment and route of administration. The frequencies of adverse effects were calculated based on the data of 1866 patients. The most frequently reported clinical adverse effects of pentavalent antimonials and pentamidine were musculoskeletal pain, gastrointestinal disturbances. Electrocardiographic QTc interval prolongation and a mild increase in liver and pancreatic enzymes were additional adverse effects of pentavalent antimonials.

Conclusion Although closer surveillance is needed for the treatment of cutaneous leishmaniasis, anti-leishmanial drugs are safe and the side effects severe enough to stop treatment are uncommon.