Severe adverse reactions to meglumine antimoniate in the treatment of visceral leishmaniasis: a report of 13 cases in the southwestern region of Brazil

Abstract

Antimony-based medications continue to be the chosen drug for visceral leishmaniasis treatment in most countries. Pentavalent antimony compounds are highly effective but frequently have adverse reactions. Although toxic effects are almost always reversible, some of them can be severe. Clinical and laboratory data of 13 patients who developed severe adverse reactions to meglumine antimoniate in a teaching hospital in southwestern Brazil in 2004-2005 were analysed. Most patients were adults (10/13), mainly at the age of 50 or older (4/13). The main severe adverse reactions were renal failure (eight episodes), pancreatitis (six episodes) and hepatic failure/hepatitis (five episodes). Six patients died in the period; all presented acute renal failure and four presented hepatic failure. Meglumine antimoniate can cause severe reactions, which can lead to death if not promptly identified. Further studies are warrented on the effect of less toxic drugs.

Renal Function Improvement with Pentavalent Antimonial Agents in Patients with Visceral Leishmaniasis

“…The main pathophysiological mechanism by which VL affects the kidneys probably includes immune complex disease as in other parasitic infections, such as malaria and schistosomiasis [9,10]. The majority of patients present with proliferative glomerulonephritis and interstitial nephritis [11,12,13].…”

Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid

“…These compounds have to be given parenterally, daily, for at least 3 weeks (typically, 20 mg of Sb/kg/day for 20 to 30 days). Antimony therapy is often accompanied by local pain during intramuscular injection and by severe side effects that include cardiotoxicity, pancreatitis, hepatotoxicity, and nephrotoxicity (4)(5)(6)(7)(8). As consequences, careful medical supervision is required, and compliance problems are common.…”

Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening

“…In Africa, only the antimonial drug sodium stibogluconate and liposomal amphotericin B are registered for treating VL. Antimonial compounds, which have been replaced by the drugs listed above for treating VL on the Indian subcontinent due to widespread antimonial resistance (31), have been used for many years against leishmaniasis, and their use is plagued by the long duration of therapy and by the associated side effects (15,18,23,31). Liposomal amphotericin B appears to be less effective against VL in Brazil (1) and in Africa (1, 14, 26) compared to India, and the expense of liposomal amphotericin B also limits its widespread use (9).…”

“…However, higher doses and a longer duration of treatment with paromomycin did result in increased efficacy against Sudanese VL (16). The standard of care in treating VL in countries of endemicity of the New World is poorly defined (24) but most likely relies on injectable pentavalent antimonial drugs (18).…”