RESUMO
INTRODUCTION: Colesevelam HCl (colesevelam) is a bile acid sequestrant initially approved by the US Food and Drug Administration (FDA) in 2000 as an adjunct to diet and exercise to lower elevated low-density lipoprotein cholesterol (LDL-C) levels in adults with primary lipidemia, as monotherapy, or in combination with a statin. More recently, the drug was approved for use in adults with type 2 diabetes mellitus (T2DM) to improve glycemic control. Thus, colesevelam is currently the only single-agent monotherapy approved by the FDA to lower both LDL-C and glycated hemoglobin (A1c) levels in adults with T2DM and elevated LDL-C. Moreover, the formulation options for colesevelam have also expanded since its original approval. MATERIALS AND METHODS: A Medline search was conducted to provide evidence to support the efficacy and safety for the use of colesevelam tablets or oral suspension preparations when treating patients with lipidemia, T2DM, or both. No limitations were placed on publication date or any other parameter. RESULTS: Clinical studies have shown that colesevelam is efficacious in lowering LDL-C levels, improving the lipid profile, and improving glycemic control by reducing both A1c and fasting plasma glucose levels in T2DM. Equilibrium and kinetics data show that colesevelam is equivalent in its tablet and oral suspension formulation. CONCLUSION: Having 2 effective oral routes enhances convenience and improves compliance, both of which contribute to maximal therapeutic outcomes. These compliance benefits are due to the ease and flexibility of preparing the powder in various beverages and the pleasant taste from the inclusion of a low-calorie citrus flavoring.
Assuntos
Alilamina/análogos & derivados , Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Alilamina/administração & dosagem , Alilamina/efeitos adversos , Alilamina/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Glicemia , LDL-Colesterol/efeitos dos fármacos , Cloridrato de Colesevelam , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas , Humanos , Hipercolesterolemia/epidemiologia , Lipídeos/sangue , Suspensões , ComprimidosRESUMO
We report the morphologic description of the bile acid sequestrants (BAS) colesevelam and colestipol, as well as the largest series of cholestyramine. Histologically similar medication resins from 4 institutions were prospectively collected over 1 year (26 specimens, 15 patients). Comorbidities included hyperlipidemia (4/15), hypertension (4/15), inflammatory bowel disease (4/15), coronary artery disease (3/15), diarrhea (7/15), hypothyroidism (2/15), and ischemic bowel (1/15). Sites of involvement included the esophagus (1/26), stomach (1/26), small intestine (1/26), ileocecal valve (1/26), and colorectum (22/26). Associated histologic diagnoses included normal (8/26), chronic mucosal injury (11/26), acute inflammation (9/26), erosion/ulceration (6/26), and cytomegalovirus (2/26). The BAS resins were histologically indistinguishable from each other; they were all eosinophilic on hematoxylin and eosin (H&E) and lacked internal "fish-scales." To validate these observations, respective medications were submitted for histologic processing; the processed medications were identical to those in the patient specimens. Rare, irregular "fracture" lines presented diagnostic pitfalls by mimicking the true "fish-scales" of Kayexalate and sevelamer. Clues to the correct identification of BAS include recognition that the "fracture" lines were subtle, irregular, and restricted to large fragments or thick sections, likely representing a processing artifact. Moreover, Kayexalate is violet on H&E and black on acid fast bacillus, and sevelamer characteristically displays a 2-tone color on H&E and is magenta on acid fast bacillus. An association with inflammatory injury was seen (15/26). We believe that the BAS are innocent bystanders in complicated patients, although we cannot exclude their ability to cause mucosal injury in specific settings.
Assuntos
Alilamina/análogos & derivados , Anticolesterolemiantes/análise , Colestipol/análise , Fármacos Gastrointestinais/análise , Intestinos/química , Resinas de Troca Iônica/análise , Adulto , Idoso , Alilamina/efeitos adversos , Alilamina/análise , Anticolesterolemiantes/efeitos adversos , Biópsia , Resina de Colestiramina/análise , Cloridrato de Colesevelam , Colestipol/efeitos adversos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mucosa Intestinal/química , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Resinas de Troca Iônica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
OBJECTIVE: Evaluate the efficacy and safety of colesevelam hydrochloride in children with heterozygous familial hypercholesterolemia (heFH). STUDY DESIGN: This was a randomized, double-blind, 41-site study in 194 children aged 10 to 17 years (inclusive) with heFH (statin-naïve or on a stable statin regimen). After a 4-week stabilization period (period I), subjects were randomized 1:1:1 to placebo, colesevelam 1.875 g/d, or colesevelam 3.75 g/d for 8 weeks (period II). All then received open-label colesevelam 3.75 g/d for 18 weeks (period III), with follow-up 2 weeks later. The primary endpoint was percent change in low-density lipoprotein (LDL)-cholesterol from baseline to week 8. Secondary endpoints included percent change in other lipoprotein variables, including non-high-density lipoprotein (non-HDL)-cholesterol. Adverse events were also evaluated. RESULTS: At week 8, a significant difference from baseline in LDL-cholesterol was reported with colesevelam 1.875 g/d (-6.3%; P = .031) and colesevelam 3.75 g/d (-12.5%; P < .001) compared with placebo. Significant treatment effects were also reported for total cholesterol (-7.4%), non-HDL-cholesterol (-10.9%), HDL-cholesterol (+6.1%), apolipoprotein A-I (+6.9%), and apolipoprotein B (-8.3%) and a nonsignificant effect for triglycerides (+5.1%) with colesevelam 3.75 g/d compared with placebo at week 8. These treatment effects were maintained during period III. CONCLUSIONS: Colesevelam significantly lowered LDL-cholesterol levels in children with heFH.
Assuntos
Alilamina/análogos & derivados , Anticolesterolemiantes/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Adolescente , Alilamina/efeitos adversos , Alilamina/farmacologia , Alilamina/uso terapêutico , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , Criança , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Cloridrato de Colesevelam , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , MasculinoRESUMO
Se presenta la experiencia clínica multicéntrica Uruguay-Chile en el tratamiento de la tiña pedis con terbinafina oral administrada por 2 semanas, con períodos de observación postratamiento a las 4 y 8 semanas de inicio del estudio. Se incluyen 67 pacientes,39 mujeres y 28 hombres, con una edad promedio de 38,9 años, que presentaban el cuadro clínico de tiña pedis (forma interdigital y formas plantares difusas, ya sea uni o bilaterales), el que fue confirmado por la presencia de dermatofitos en el cultivo micológico inicial (79,1 por ciento de los casos trichophyton rubrum). Se evaluaron signos clínicos variados: eritema, descamación, vesiculización, presencia de pústulas, exudación, costras y síntoma prurito. La evaluación micológica se efectuó mediante examen directo y cultivo. Los signos y síntomas clínicos mejoraron durante todo el seguimiento, alcanzando entre 61,2 por ciento al 100 por ciento de mejoría total de estos parámetros a las 8 semanas de seguimiento. Los exámenes micológicos se fueron negativizando progresivamente, alcanzando en la evaluación final a las 8 semanas un 92 por ciento de exámenes directos y un 85 por ciento de cultivos negativos, respectivamente. Recaídas con cultivos micológicos positivos fueron observadas en 2 casos (4,3 por ciento). El medicamento fue, en general, bien tolerado, y los efectos adversos más frecuentes fueron gastrointestinales, presentes en 7 pacientes. No se registraron alteraciones de parámetros bioquímicos de significación. En conclusión, la terbinafina (LAMISIL) se presenta como una nueva medicación antimicótica sistémica de alta eficacia en cortos períodos de tratamiento en variadas formas de tiña pedis