Randomized Controlled Clinical Trial to Access Efficacy and Safety of Miltefosine in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) guyanensis in Manaus, Brazil

Chrusciak‐Talhari, Anette; Dietze, Reynaldo; Talhari, Carolina; Silva, Roberto Moreira da; Yamashita, Ellen Priscila Gadelha; Penna, Gerson Oliveira; Machado, Paulo Roberto Lima; Talhari, Sinésio

doi:10.4269/ajtmh.2011.10-0155

Cited by 141 publications

(149 citation statements)

References 18 publications

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“…17 Sb-unresponsive CL is being seen clinically in the sense that recent cure rates of New World L. (Viannia) CL treated with systemic Sb are surprisingly low for a standard therapy, approximately 50-75%. [18][19][20][21][22] An undecided issue is whether there is a correlation between in vitro and clinical data, whether parasite resistance is the cause of clinical unresponsiveness. For Leishmania tropica from Iran, the mean effective dose (ED50) for parasites from 165 lesions that responded to systemic or ILSb was 4.6 μg/mL, whereas the mean ED50 for parasites from 16 lesions that did not respond was 19 μg/mL.…”

Section: 15mentioning

confidence: 99%

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Soto¹,

Paz²,

Rivero³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm 2 lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm 2 ). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm 2 lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.

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Section: 15mentioning

confidence: 99%

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Soto¹,

Paz²,

Rivero³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…Miltefosine has recently been shown to be non-inferior to meglumine antimoniate in the treatment of pediatric CL in Colombia, 3 and its efficacy in children is corroborated by clinical trials in populations where Leishmania guyanensis and L. braziliensis are endemic in Brazil. 4,5 However, guidelines for the treatment of children with CL have not yet been implemented and access to the pediatric formulation of miltefosine is limited. Notably, neither data nor guidelines are available for treatment of children under 2 years of age with CL with any antileishmanial drug.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Blanco¹,

Cossio²,

Martinez³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Treatment alternatives have seldom been evaluated in children with cutaneous leishmaniasis (CL). We examine the clinical/epidemiological profile of children with CL considering international guidelines for local treatment. Descriptive analyses were conducted using International Center for Medical Research and Training (CIDEIM) case reports of parasitologically diagnosed patients 14 years of age from 2004 to 2010. Eligibility for local treatment based on World Health Organization/Pan American Health Organization (WHO/PAHO) criteria was determined. Among 380 children, 90% presented lesions of 3 months duration, 54% presented single lesions 30 mm in diameter, and 45% were 5 years old. Lesions on the head and neck were more frequent among children 0-5 years, and lesions below the head/neck were more frequent among 11-to 14-year-old children (P = 0.004). Using PAHO and WHO criteria, 26% and 53% of children, respectively, were eligible for local treatment. Recommended local treatments for New World CL have potential but limited applicability in children. Individual risk-benefit assessment and effectiveness data in children may increase eligibility.

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“…It has achieved relatively high cure rates in the treatment of visceral (8,26,41,52,54), New World cutaneous (11,44,48,50,57), Old World cutaneous (30,56) and even difficult-to-treat mucocutaneous (49,51) leishmaniasis.…”

mentioning

confidence: 99%

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

Dorlo

Huitema

Beijnen

et al. 2012

Antimicrob Agents Chemother

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bOnly anecdotal data are available on the pharmacokinetics (PK) of miltefosine in children suffering from visceral leishmaniasis (VL). While failure rates were higher in children with VL, steady-state concentrations appeared lower than those seen with adults. We hypothesized that the current linear dosage (in milligrams per kilogram of body weight) is too low for children and that a new dosing algorithm based on an appropriate body size model would result in an optimal exposure. A population PK analysis was performed on three historic pooled data sets, including Indian children, Indian adults, and European adults. Linear and allometric scaling of PK parameters by either body weight or fat-free mass (FFM) was evaluated for body size models. Based on the developed PK model, a dosing algorithm for miltefosine in children and adults was proposed and evaluated in silico. The population PK model employing allometric scaling fitted best to the pooled miltefosine data. Allometric scaling by FFM reduced between-subject variability, e.g., for drug clearance, from 49.6% to 32.1%. A new allometric miltefosine dosing algorithm was proposed. Exposure to miltefosine was lower in children than adults receiving 2.5 mg/kg/day: a C max of 18.8 g/ml was reached by 90% of adults and 66.7% of children. The allometric daily dose resulted in similar levels of exposure to miltefosine for adults and children. The use of a new allometric dosing algorithm for miltefosine in VL patients results in optimal exposure to miltefosine in both adults and children and might improve clinical outcome in children.V isceral leishmaniasis (VL) or kala-azar (Hindi for "black fever") has been classified as one of the world's "most neglected diseases" (62), and of all the parasitic diseases, it ranks third in terms of morbidity and mortality after only malaria and lymphatic filariasis (38). The World Health Organization (WHO) reported in 2004 that leishmaniasis is responsible for around 50,000 deaths and almost 2 million disability-adjusted life-years per year, approximately half of which can be attributed to children from lowincome countries (38, 60), but in reality the burden of leishmaniasis is probably much larger due to massive underreporting of both cases and deaths in the often remote areas where leishmaniasis is prevalent (47).Miltefosine (hexadecylphosphocholine; marketed by Paladin Laboratories Inc. as Impavido) is the newest addition to the small repertory of antileishmanial drugs and to date is the only drug that can be administered orally. It has achieved relatively high cure rates in the treatment of visceral (8, 26, 41, 52, 54), New World cutaneous (11,44,48,50,57), Old World cutaneous (30, 56) and even difficult-to-treat mucocutaneous (49, 51) leishmaniasis.During the development of miltefosine, two clinical trials were designed to investigate the efficacy and safety of miltefosine in children (Ͻ12 years of age) in which a total of 119 pediatric patients were enrolled, employing dosages linearly extrapolated from the daily adult dosage (in ...

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Randomized Controlled Clinical Trial to Access Efficacy and Safety of Miltefosine in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) guyanensis in Manaus, Brazil

Cited by 141 publications

References 18 publications

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis

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