High frequency of serious side effects from meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients.

Abstract

Abstract. Organic pentavalent antimonials are one of the mainstays of treatment for visceral leishmaniasis (VL). Few data are available on the toxicity and efficacy of these drugs at the dosing schedule recommended by the Centers for Disease Control and Prevention (CDC) (Atlanta, GA). We analyzed 25 VL episodes in human immunodeficiency virus (HIV)-infected patients who were treated with meglumine antimoniate (MA) at the CDC-recommended dose in southern Spain. Adverse effects were observed in 14 (56%) VL episodes. In 7 (28%), treatment with MA was permanently discontinued due to serious adverse effects that included acute pancreatitis, acute renal failure, and leukopenia. Three (12%) patients died during therapy due to severe acute pancreatitis attributable to MA. The dosing regimen of MA currently recommended for treating VL is associated with a high rate of serious side effects in HIV-1-infected patients.Visceral leishmaniasis (VL) caused by Leishmania infantum is endemic in countries bordering the Mediterranean basin. It has been increasingly recognized that it affects human immunodeficiency virus type-1 (HIV-1)-infected patients, not only in this endemic area 1 , but also in non-endemic western countries. 2,3 Organic pentavalent antimonials (Sb V ) are one of the first-line drugs recommended by the Word Health Organization (WHO) for treating VL in the Mediterranean area. 4 In 1982, WHO (unpublished data) advocated treatment with 20 mg of Sb V /kg of body weight, with a maximum dose of 850 mg/day. The Centers for Disease Control (CDC) (Atlanta, GA) recommended in 1992 to remove the upper limit dose. 5 Data that supported this recommendation stemmed from clinical trials with patients not infected with HIV. 5 It was reported that higher daily doses without an upper limit resulted in better responses. Side effects were regarded as reversible and rarely severe.Patients with VL coinfected with HIV have a poor response to Sb V therapy. 1 Microbiologic cure is observed in less than half the cases and relapses are frequent. [6][7][8][9] In this setting, toxic effects of Sb V have seldom been reported in previous studies. 6,10,11 However, the dose of Sb V used in these patients was limited to a maximum of 850 mg/day. 6-12 Therefore, we assume that a low dose was administered. Thus, few data are available on efficacy and safety of the currently recommended Sb V dosing schedule to treat VL in HIV-1-infected individuals. 1 We provide herein data on toxicity and efficacy of meglumine antimoniate (MA) at a dose of 20 mg/kg of body weight/day with no dose limit in HIV-1-infected patients with VL. PATIENTS AND METHODSPatients. Fifty-one episodes of VL were diagnosed in 46 HIV-1-infected patients attending 2 University Hospital Acquired Immunodeficiency Syndrome (AIDS) care units in Seville, Spain from October 1993 to December 1997. Based on the diagnosis of the responsible physician, 25 VL episodes (49%) were treated with MA following the dosing schedule recommended by CDC in 1992. 5 Twenty-four were initial episodes and 1 w...

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

“…The cause of increased clinical pancreatitis with antimonials in coinfected patients is not clear (78). It is possible that antimonial toxicity selectively affects the sickest patients, such as those with VL-HIV coinfection, because the pentavalent antimonial is reduced to the toxic trivalent antimonial to a greater extent in these patients.…”

“…In an evaluation of pentavalent antimoniate treatment, adverse effects were observed in 56% of patients, and therapy had to be discontinued permanently due to serious adverse effects (mainly acute pancreatitis) in 28% of patients. A further 12% of patients died due to severe pancreatitis directly attributable to treatment (78). Although data from Africa and India are lacking, the high frequency of vomiting and mortality among antimonial-treated HIV-positive patients in Ethiopia suggests that similar toxicity occurs (215,216).…”

“…The success rates in published studies vary greatly due to high levels of dropout and early death (78,134,135,141,189). Drug-induced pancreatitis was the most common cause of treatment discontinuation and death (78,134,135,189).…”

Importance of Nonenteric Protozoan Infections in Immunocompromised People

“…However, these compounds are quite toxic (17,125,149,158,362). Furthermore, due to their widespread use for over 70 years, resistance has meant that antimonials are virtually useless in parts of India and Nepal (24,374).…”

Drug policy for visceral leishmaniasis: a cost‐effectiveness analysis

“…Antimonials are not an ideal drug; they have to be administered parenterally over a period of 28-30 days, generally requiring hospitalization. Antimonials have shown rare but serious side effects, such as cardio, pancreas and liver toxicity (Gasser et al 1994;Sundar et al 1998c;Thakur et al 1998;Rijal et al 2003), whose importance increases if the patient is coinfected with HIV (Delgado et al 1999;Laguna et al 1999). Resistance to antimonials has been reported in up to 65% of patients in some villages of Bihar, India (Sundar 2001).…”