Case and Research Letter
Miltefosine to Treat Childhood Cutaneous Leishmaniasis
Tratamiento de leishmaniasis cutánea infantil con miltefosina
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A) Placa eritematoviolácea exudativo-costrosa muy dolorosa de 8 x 6 cm en el brazo de un niño de 10 años. B) Control seis meses después del tratamiento con miltefosina oral. Placa marronácea de aspecto residual en el brazo. El paciente se mantenía asintomático.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P.J. Barba, D. Morgado-Carrasco, A. Quera" "autores" => array:3 [ 0 => array:2 [ "nombre" => "P.J." "apellidos" => "Barba" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Quera" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173102100452X?idApp=UINPBA000044" "url" => "/00017310/0000011300000008/v1_202208290519/S000173102100452X/v1_202208290519/es/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S000173102100452X" "issn" => "00017310" "doi" => "10.1016/j.ad.2020.11.033" "estado" => "S300" "fechaPublicacion" => "2022-09-01" "aid" => "2835" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2022;113:827-31" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CARTA CIENTÍFICO-CLÍNICA</span>" "titulo" => "Tratamiento de leishmaniasis cutánea infantil con miltefosina" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "827" "paginaFinal" => "831" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Miltefosine to Treat Childhood Cutaneous Leishmaniasis" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 831 "Ancho" => 1250 "Tamanyo" => 142771 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Leishmaniasis cutánea infantil. A) Placa eritematoviolácea exudativo-costrosa muy dolorosa de 8 x 6 cm en el brazo de un niño de 10 años. B) Control seis meses después del tratamiento con miltefosina oral. Placa marronácea de aspecto residual en el brazo. El paciente se mantenía asintomático.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P.J. Barba, D. Morgado-Carrasco, A. Quera" "autores" => array:3 [ 0 => array:2 [ "nombre" => "P.J." "apellidos" => "Barba" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Quera" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173102100452X?idApp=UINPBA000044" "url" => "/00017310/0000011300000008/v1_202208290519/S000173102100452X/v1_202208290519/es/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => " Miltefosine to Treat Childhood Cutaneous Leishmaniasis" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T827" "paginaFinal" => "T831" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P.J. Barba, D. Morgado-Carrasco, A. Quera" "autores" => array:3 [ 0 => array:4 [ "nombre" => "P.J." "apellidos" => "Barba" "email" => array:1 [ 0 => "paulabarba_@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Quera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, H.I.G.A Prof. Dr. Rodolfo Rossi, La Plata, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Patología, Hospital de Figueres, Fundació Salut Empordà, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de leishmaniasis cutánea infantil con miltefosina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 832 "Ancho" => 1251 "Tamanyo" => 131624 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Childhood cutaneous leishmaniasis. A, Very painful crusted, exudative, erythematous violaceous plaque (8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>cm) on the arm of a 10-year-old boy. B, Lesion control achieved 6 months after treatment with oral miltefosine. Residual brownish plaque on the arm. The patient remained asymptomatic.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Treatment of cutaneous leishmaniasis (CL) is complex, and depends on the <span class="elsevierStyleItalic">Leishmania</span> species, the site of inoculation, the clinical presentation, and the patient's age. Parenterally administered drugs, mainly pentavalent antimonials administered intravenously or intramuscularly, are generally reserved for complex forms or immunocompromised patients. Local treatments are the most commonly used, and include intralesional pentavalent antimonials, thermotherapy, and cryotherapy. These therapies can be very painful, have serious potential adverse effects, and can be less effective in children.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> Miltefosine, an oral agent with recognized efficacy for the treatment of leishmaniasis, may be a good option in these cases.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 10-year-old boy (35<span class="elsevierStyleHsp" style=""></span>kg) of Moroccan origin, with no relevant medical history, was seen for a painful skin lesion on the arm that had appeared 6 months earlier, 1 week after traveling to Morocco. Physical examination revealed a crusted, exudative, erythematous violaceous plaque measuring 8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Biopsy showed a lymphohistiocytic infiltrate with intracellular amastigotes (Leishman-Donovan bodies) in the dermis, based on which the patient was diagnosed with CL. Due to the child's age, his poor tolerance for medical procedures, the potential adverse effects of intralesional pentavalent antimonials, and their reduced efficacy in children aged less than 12 years,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> it was decided to begin treatment with miltefosine (75<span class="elsevierStyleHsp" style=""></span>mg/d) for 28 days. The results of laboratory tests performed before and during treatment, including a complete blood count and kidney and liver function profiles, were normal. After 2 weeks of treatment the patient no longer presented pain, and after 4 weeks a marked clinical improvement was observed, with the presence of residual hyperpigmentation. At follow-up 6 months later, the patient remained asymptomatic, with a residual plaque on the arm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment of leishmaniasis in children can be difficult: they present a higher percentage of facial lesions, have a significantly lower response rate to antimonials than adults, have poorer adherence to injectable treatments, and are more susceptible than adults to potential systemic toxicity associated with standard treatments<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Miltefosine is an alkylphosphocholine that was initially developed as an antitumor agent, after which its anti-<span class="elsevierStyleItalic">Leishmania</span> activity was discovered. In 2014 it was approved by the Food and Drug Administration (FDA) for the treatment of visceral, cutaneous, and mucocutaneous leishmaniasis in patients aged ≥12 years (≥30<span class="elsevierStyleHsp" style=""></span>kg), and is currently the only authorized oral drug for this indication.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> Adverse effects occur in more than half of all patients, but are predominantly mild and well tolerated. Almost 90% of adverse effects are grade 1, consisting mainly of diarrhea, vomiting, transient increases in transaminase levels, and mild renal dysfunction, and do not usually require treatment interruption<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,4</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Multiple clinical trials have demonstrated a high response rate to miltefosine in patients with visceral and cutaneous leishmaniasis. A recent meta-analysis reported similar responses in CL patients infected with <span class="elsevierStyleItalic">Leishmania braziliensis</span> treated with either miltefosine or antimonials, but found that miltefosine was significantly superior in patients infected with parasite species other than <span class="elsevierStyleItalic">L. braziliensis</span>.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> Another recent meta-analysis evaluating CL treatments in children aged ≤12 years found a satisfactory response in 68% to 82.6% of CL cases treated with miltefosine.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> A randomized clinical trial conducted in Colombia included 116 CL patients aged 2–12 years, who were treated with intramuscular meglumine antimoniate (20<span class="elsevierStyleHsp" style=""></span>mg/kg/d for 20<span class="elsevierStyleHsp" style=""></span>d) or oral miltefosine (1.8–2.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d for 28<span class="elsevierStyleHsp" style=""></span>d).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Miltefosine showed a response rate of over 80%, which was noninferior to that of meglumine antimoniate, and a lower rate of adverse effects. Numerous clinical cases and case series have demonstrated the utility of miltefosine for the treatment of Old World CL,<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">8,9</span></a> although there are limited pediatric data available.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Miltefosine is detectable in cells and plasma up to 1 and 6 months after treatment, respectively.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> This may explain why the clinical response progressively improves after discontinuation of treatment. Some studies have shown that children may have lower plasma and intracellular concentrations of miltefosine than adults,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> which may influence the therapeutic response.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Despite being the only oral agent approved for the treatment of leishmaniasis, its good efficacy and safety profile, and its inclusion in the World Health Organization's list of essential drugs, miltefosine is considered an orphan drug given its limited availability worldwide. In Europe, it is registered only in Germany (in Spain it must be requested as a foreign medication), and constitutes a high cost for health systems.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> In Spain it costs approximately €2600 (56 hard 50-mg capsules), which is significantly more expensive than imiquimod, daylight photodynamic therapy, and intralesional antimonials. However, it could be cost-effective when considering adherence, efficacy, the indirect costs of lost time, adverse events, and direct costs to the patient.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> The fact that miltefosine is no longer patent-protected should facilitate the development of lower-cost generic products.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Daylight photodynamic therapy is another therapeutic alternative for childhood CL. A novel study reported a high response rate when the product was applied by the patient (or their relatives) once per week until clinical resolution, with minimal adverse effects.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Children may show poorer adherence to standard CL therapy, which can have potentially serious adverse effects in these patients. Miltefosine can be a useful alternative for the treatment of leishmaniasis in these cases owing to its high efficacy, oral route of administration, and low toxicity.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 832 "Ancho" => 1251 "Tamanyo" => 131624 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Childhood cutaneous leishmaniasis. A, Very painful crusted, exudative, erythematous violaceous plaque (8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>cm) on the arm of a 10-year-old boy. B, Lesion control achieved 6 months after treatment with oral miltefosine. Residual brownish plaque on the arm. The patient remained asymptomatic.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: FDA, Food and Drug Administration; HIV, human immunodeficiency virus; IV, intravenous; MC, mucocutaneous; L.L., <span class="elsevierStyleItalic">Leishmania (Leishmania); L.V., Leishmania (Viannia);</span> Sb, antimoniate; Sb<span class="elsevierStyleSup"><span class="elsevierStyleItalic">V</span></span>, pentavalent antimoniate or antimoniate salts.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose and route of administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse effects \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liquid nitrogen applied for 15–20<span class="elsevierStyleHsp" style=""></span>s up to 1–2<span class="elsevierStyleHsp" style=""></span>mm around the border of the lesion. Repeat 3 times per session. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema, edema, blister, residual hypopigmentation or hyperpigmentation, scarring \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recent, small (<3<span class="elsevierStyleHsp" style=""></span>cm diameter) lesions, <5 plaques. Do not use in cosmetically or functionally important areas (face, joints) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment is repeated every 3 wk until cure is achieved \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thermotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Superficial application of heat (50<span class="elsevierStyleHsp" style=""></span>°C) for 30<span class="elsevierStyleHsp" style=""></span>s up to 1–2<span class="elsevierStyleHsp" style=""></span>mm around the lesion border. Requires local anesthesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema, edema, burns, residual hypopigmentation or hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Few (<5), small (<3<span class="elsevierStyleHsp" style=""></span>cm in diameter) lesions in areas that are neither cosmetically nor functionally important (i.e. avoiding face). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thermosensitive species: <span class="elsevierStyleItalic">L.L. major, L.L. tropica, L.V. panamensis</span>, and <span class="elsevierStyleItalic">L.V. braziliensis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imiquimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical 5% cream, 3 times per wk for 8 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema, pruritus, edema, ulceration. Headache, flu-like syndrome, myalgia (uncommon) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Few, small lesions, species not associated with mucosal or lymphocutaneous involvement. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Can reduce the duration of administration of pentavalent antimonials when both are administered in combination. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Variable efficacy in monotherapy<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paromomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical, creams or ointments. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema, itching, pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Few, small (≤5<span class="elsevierStyleHsp" style=""></span>cm) ulcers due to <span class="elsevierStyleItalic">L.L. major</span>, without lymphocutaneous involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Different formulations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Photodynamic therapy/daylight activated photodynamic therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weekly application until lesion resolution<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema, itching, pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Few, small lesions, species not associated with mucosal or lymphocutaneous involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentavalent antimonials</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intralesional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain, local allergic reaction, edema, pruritus, and erythema. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Few, small lesions. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>Sodium stibogluconate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Injection of 0.2–5<span class="elsevierStyleHsp" style=""></span>mL per session every 3–7<span class="elsevierStyleHsp" style=""></span>d, for a total of 5–8 treatment sessions (or until clinical resolution) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nausea, abdominal pain, headache, myalgia and arthralgia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Species not associated with mucosal or lymphocutaneous involvement. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>Meglumine antimoniate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular or intravenous route \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased levels of pancreatic enzymes and serum transaminases, mild nonspecific leukopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Species associated with mucosal or lymphocutaneous involvement, >5 lesions, >3<span class="elsevierStyleHsp" style=""></span>cm in diameter, in cosmetically or functionally important areas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>mg Sb<span class="elsevierStyleSup">V</span>/kg/d, infused over 15–30<span class="elsevierStyleHsp" style=""></span>min, for 20<span class="elsevierStyleHsp" style=""></span>d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiotoxicity and electrocardiographic abnormalities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Azoles</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral administration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nausea, vomiting, diarrhea, hepatotoxicity. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cutaneous, lymphocutaneous, and MC leishmaniasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-<span class="elsevierStyleHsp" style=""></span>Fluconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12<span class="elsevierStyleHsp" style=""></span>mg/kg/d for 6 wk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased serum transaminases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Variable efficacy depending on \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-<span class="elsevierStyleHsp" style=""></span>Itraconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–10<span class="elsevierStyleHsp" style=""></span>mg/kg/d for 42–56<span class="elsevierStyleHsp" style=""></span>d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Species. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentamidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular administration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pancreatitis, hypotension. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exclusively for <span class="elsevierStyleItalic">L.V. guyanensis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4<span class="elsevierStyleHsp" style=""></span>mg/kg every other day, 3–4 doses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prolongation of QT interval. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperpotassemia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nephrotoxicity. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased serum transaminase levels \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amphotericin</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-<span class="elsevierStyleHsp" style=""></span>Amphotericin deoxycholate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5–1.0<span class="elsevierStyleHsp" style=""></span>mg/kg IV daily or every other day for a cumulative dose of 15–30<span class="elsevierStyleHsp" style=""></span>mg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nephrotoxicity. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complex lesions (species associated with MC involvement, >5 lesions, lesions >3<span class="elsevierStyleHsp" style=""></span>cm, cosmetically important areas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-<span class="elsevierStyleHsp" style=""></span>Liposomal amphotericin B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3<span class="elsevierStyleHsp" style=""></span>mg/kg/d IV for 5<span class="elsevierStyleHsp" style=""></span>d and then a sixth dose on day 10 or daily for 7<span class="elsevierStyleHsp" style=""></span>d for a cumulative dose of 18–21<span class="elsevierStyleHsp" style=""></span>mg/kg<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypokalemia.Anemia.Peripheral venous phlebitis.Infusion related fever.Prolonged QT interval \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">[e.g. face], functionally important areas, lymph node involvement), severe forms (visceral or mucosal), lesions resistant to first-line therapy, immunocompromised patients or those with HIV coinfection \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Can be applied by the patient or relatives once per week; sun exposure for 2<span class="elsevierStyleHsp" style=""></span>h; repeat until clinical cure.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Dosage based on treatment of visceral leishmaniasis.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Available Treatments for Cutaneous Leishmaniasis in Children.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Mechanism of action \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Posology \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Formulation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Adverse effects \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Contraindications \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Interactions \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UnknownAttributed to a possible interaction with phospholipids and steroids in parasitic cell membranes, inhibition of mitochondrial function, and apoptosis-like cell death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Children:2–11 y: 2.5<span class="elsevierStyleHsp" style=""></span>mg/kg for 28 d≥12 y:<25<span class="elsevierStyleHsp" style=""></span> kg: 0<span class="elsevierStyleHsp" style=""></span>mg/d for 28<span class="elsevierStyleHsp" style=""></span>d<span class="elsevierStyleMonospace">></span>25<span class="elsevierStyleHsp" style=""></span>kg: amoxicillin 50<span class="elsevierStyleHsp" style=""></span>mg twice per day for 28<span class="elsevierStyleHsp" style=""></span>dAdults:30–44<span class="elsevierStyleHsp" style=""></span>kg: amoxicillin 50<span class="elsevierStyleHsp" style=""></span>mg twice per day for 28 d≥45<span class="elsevierStyleHsp" style=""></span>kg: amoxicillin 50<span class="elsevierStyleHsp" style=""></span>mg 3 times per day for 28 d.Administer with meals to decrease gastrointestinal side effects<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Breakable hard capsules, 50<span class="elsevierStyleHsp" style=""></span>mg (Impavido®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Common (>10%): anorexia, nausea, vomiting, diarrhea, abdominal pain. Headache, dizziness.Thrombocytopenia (<150<span class="elsevierStyleHsp" style=""></span>000: 62%; <50<span class="elsevierStyleHsp" style=""></span>000: 2%).Increased serum transaminase levels (3×, 94%; 3–5×, 6%).Increased serum creatinine (≥1.5 times above baseline value, 10–25%).Rare (1–10%):Drowsiness, malaise, fatigue, paresthesia.Pruritus, cellulitis, skin rash, Stevens-Johnson syndrome, urticaria.Testicular pain, testicular swelling.Lymphangitis, anemia, lymphadenopathy.Other: weakness, fever, agranulocytosis, decreased ejaculate volume, increased serum bilirubin, jaundice, melena, seizures, thrombocytopenia, pancreatitis<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HypersensitivitySjogren–Larsson syndrome.Pregnancy (toxicity studies in rats indicate embryotoxicity, fetotoxicity, and teratogenicity). Women of childbearing age should use effective contraception during and for 3–5 months after completing treatment.There are no data on risk during lactation: administration is not recommended \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No significant interactions known \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">No information is available on dose adjustment in cases of renal or hepatic insufficiency.</p>" ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">One case of fatal acute pancreatitis has been reported.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Mechanism of Action, Dosage, Adverse Effects, Contraindications, and Interactions of Miltefosine.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Visceral Leishmaniasis-Optimum treatment options in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. 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