Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III-A, with 12 (20.3%) patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

Efecto del probiótico Saccharomyces boulardii en la prevención de la diarrea asociada con antibióticos en adultos ambulatorios en tratamiento con amoxicilina / Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment

Background: Antibiotic-associated diarrhea is one of the most common adverse effects of antimicrobials. Any antimicrobial can potentially produce diarrhea but beta-lactamics have a higher risk. Among these, amoxicillin is widely indicated in ambulatory practice. One ofthe alternatives suggested to prevent antibiotic-associated diarrhea, is the use of the probiotic Saccharomyces boulardii. Aim: To evalúate whether the concomitant use of Saccharomyces boulardii and amoxicillin can prevent antibiotic associated diarrhea in ambulatory adults with acute infections diseases, without provoking other adverse effects. Material and Methods: Eighty six adults (aged 15 to 81 years) with acute infectious diseases, excluding those arising in the gastrointestinal tract, that received a prescription of oral amoxicillin for 5 to 10 days, were included. In a controlled randomized, double blind trial, 41 patients were assigned to receive lyophilized Saccharomyces boulardii (500 mg/day) duríng 12 days, and 45 patients were assigned to placebo for the same period. Results: Ten percent of patients (9/86) reported acute diarrhea, 9,8 percent (4/41) in the experimental group and 11.196 (5/45) in the control group (p = 100). No adverse effects were associated to the use of the probiotic. Conclusions: Saccharomyces boulardii (500 mg/day) did not prevent diarrhea related to amoxicillin.

Diarrea crónica por ingesta de laxantes / Chronic diarrhea due to laxatives

La constipación crónica es una condición muy frecuente en el sexo femenino. La toma habitual y muchas veces, autoprescrita de laxantes es igualmente frecuente. Los mucílagos y los lubricantes no tienen riesgos no así los irritantes drásticos que pueden producir cuadros diarreicos crónicos graves

Diarreas inducidas por antibioticos: adquisiciones recientes sobre clostridium difficile / Antibiotics induced diarrhea-recent knowledge about clostridium difficile

From the beginning of the antibiotherapy, diarrhea frequently ocurred as a side effect of the treatment. The spectrum of diarrheal disease associated with antibiotic therapy ranges from antibiotic associated diarrhea and colitis, to the more severe pseudomembranous colitis, wich is always associated with Clostridium difficile (CD). Because most of the antibiotics are not active against this sporulated Gram positive anaerobe. The pathogenic process accurs only by production of toxins. CD is now recognized as one of the most important hospital infections. Although therapy is available for the majority of patients with CD infection, pseudomembranous colitis is a serious disease which, if untreated, can lead to major complications.