Potential drug-drug interactions in hospitalized patients undergoing systemic chemotherapy: a prospective cohort study.

BACKGROUND: Adverse drug-drug interactions (DDI) are a major cause of morbidity and mortality in susceptible populations. Cancer patients are a population at high risk for DDI especially because they commonly receive several drugs concomitantly. The knowledge about the most common interactions between drugs used in oncology inpatients is essential to reduce drug-related problems and increase the safety and efficacy of the therapy. OBJECTIVE: To assess the frequency of potential DDI throughout the hospital stay of cancer patients undergoing systemic chemotherapy, describe their epidemiology, and identify risk factors for major DDI. Setting An oncology-hematology inpatient unit of a public hospital in southern Brazil. METHOD: Drug prescriptions were prospectively reviewed throughout the hospital stay of patients admitted for systemic chemotherapy. Descriptive statistics and Poisson regression were used for data analysis. MAIN OUTCOME MEASURE: Potential DDI and their characteristics. RESULTS: The cohort consisted of 113 patients, who used a mean of 8.9 ± 2.7 drugs/day. All patients had at least one potential DDI (median, 7.0/patient; 25th-75th percentile, 3.5-12.0), and 46 % of the patients had at least one DDI classified as major, i.e. that it may result in death, hospitalization, permanent injury, or therapeutic failure. Only 13.7 % of all interactions involved antineoplastic agents, identified in 62.8 % of patients. Most interactions were of moderate severity, 6.4 % were major, and 8.5 % had a recommendation for therapy modification. Multivariate analysis revealed mean number of drugs prescribed [relative risk (RR) for each additional drug: 1.12; 95 % confidence interval (CI) 1.07-1.17; P < 0.01] and age ≥60 years (RR 1.48; 95 % CI 1.03-2.14; P < 0.01) as independent risk factors for major DDI. CONCLUSION: Potential DDI were highly frequent in this cohort. Older age and number of drugs prescribed were more likely to lead to major interactions. Prospective surveillance is required to detect adverse DDI, aiming primarily at reducing the risk of toxicity or treatment failure.

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence?

BACKGROUND: Introduction of the monoclonal antibody rituximab to chemotherapy regimens has substantially improved disease-free and overall survival in patients with non-Hodgkin lymphomas (NHL). The short-term safety of this drug has been widely reported, but there are few data on long-term safety, which suggests that these patients require prolonged follow-up. AIM OF THE REVIEW: To review the literature on follow-up models, with a focus on the safety of rituximab therapy for diffuse large B-cell lymphoma and follicular lymphoma. METHOD: The Cochrane Library, Embassy, Lilacs, Medline, and Scirus databases were searched for systematic reviews and randomized controlled trials. Furthermore, textbooks and journals on pharmaceutical care and institutional websites were searched for patient management recommendations. The outcomes were follow-up models and grade 3, 4, and 5 adverse reactions. RESULTS: Five systematic reviews and eight clinical trials or updates describing patient follow-up or reporting adverse reactions were identified. Only one systematic review and seven clinical trials reported follow-up routines for patients receiving rituximab, including information on staging, frequency of reassessment, and laboratory tests, as well as pre-infusion care and management of acute or delayed adverse reactions. Five systematic reviews and four clinical trials reported data on statistically significant adverse reactions (fever, leukopenia, infection). Four guidelines or institutional protocols for treatment and follow-up were identified, as well as seven studies describing experiences in the implementation of pharmaceutical care for oncology patients, but none were specifically focused on follow-up of patients receiving rituximab for NHL. CONCLUSION: Although some systematic reviews and clinical trials contain guidance on follow-up of patients receiving rituximab for NHL, there are no validated strategies for systematic follow-up of these patients with a focus on safety. As there are few data on long-term safety profile of these novel treatments, monitoring strategies should be developed and implemented to ensure safe and optimized use of drugs recently added to the therapeutic arsenal of clinical oncology.

Effectiveness of a Protective Environment implementation for cancer patients with chemotherapy-induced neutropenia on fever and mortality incidence.

In a quasiexperimental study conducted to evaluate the impact of a Protective Environment implementation, febrile neutropenia (P = .009), overall mortality (P = .001), and 30-day adjusted mortality (P = .02) were reduced in cancer patients with chemotherapy-induced neutropenia. Our study highlights the potential success of a set of prevention measures mainly designed to reduce invasive environmental fungal infections in allogeneic hematopoietic stem cell transplant patients, in reducing fever and mortality among neutropenic cancer patients.

Microbiological findings in febrile neutropenic patients in a tertiary hospital of Southern Brazil / Achados microbiológicos em pacientes neutropênicos febris em um hospital terciário do sul do Brasil

Introdução: Neutropenia é um forte fator de risco para infecção. A prevalência de bactérias Gramnegativas diminuiu no início da década de 90 e a frequência de bactérias Gram-positivas aumentou em 55 a 70% em todos os episódios de bacteremia. Porém, mais recentemente, infecções por bactéria Gram-negativas ressurgiram. O objetivo deste estudo é descrever os achados microbiológicos em uma coorte de pacientes neutropênicos febris em um hospital terciário de ensino do sul do Brasil.Metodologia: Estudo coorte para avaliação da implementação de um protocolo clínico para o tratamento de pacientes neutropênicos febris. Foram incluídos prospectivamente pacientes com neutropenia febril (NF) admitidos entre janeiro de 2004 e dezembro de 2005 no Hospital de Clínicas de Porto Alegre. Controles históricos foram selecionados de visitas de pacientes entre março de 2001 e abril de 2003 ou antes do protocolo clínico ter sido implementado.Resultados: Nos períodos do estudo de 2004-2005 e 2001-2003, foram documentados 164 e 159 patógenos, respectivamente. Em 93 de 190 episódios (48,9%) e 84 de 193 episódios (43,5%) foram documentadas infecções microbiológicas.

Infecções fúngicas foram documentadas em poucos episódios (6,1 e 5,7%). Observou-se uma prevalência de 52,8% de bactérias Gram-positivas e 47,2% de bactérias Gram-negativas no período de 2001-2003. No período de 2004-2005, foram observadas 38,1% de bactérias Gram-positivas e 61,9% de bactérias Gram-negativas (P=0,012).Também houve um aumento significativo da prevalência de Pseudomonas aeruginosa no segundo período de estudo (1,9 para 11,6%; P<0,001). Em 2004-2005, seis isolados eram multirresistentes(31,6%). A prevalência de Staphylococcus resistente à oxacilina foi de 53,5 e 65,8% nos primeiros e segundos períodos, respectivamente (P=0,23).Conclusão: Os patógenos documentados neste estudo são os mais comuns em pacientes neutropênicos febris, mas a emergência de Pseudomonas aeruginosa resistente a multidrogas é uma preocupação.

Background: Neutropenia is a major risk factor for infection. The prevalence of Gram-negative bacteria decreased in the early nineties, while the frequency of Gram-positive bacteria increased from between 55 to 70% of all bacteremia episodes. Even more recently there has been a resurgence of Gram-negative infections. The aim of this report is to describe the microbiological findings in a cohort of febrile neutropenic patients in a tertiary teaching hospital of Southern Brazil.Methods: This was a cohort study designed to evaluate the implementation ofa clinical protocol for treatment of febrile neutropenic patients. Prospectively included in our study were patients with febrile neutropenia (FN) admitted between January 2004 and December 2005 at the Hospital de Clínicas of Porto Alegre.Historical controls were selected from patient visits recorded between March 2001 and April 2003 - or recorded before the clinical protocol was introduced.Results: During the 2004-2005 and 2001-2003 study periods, 164 and 159 pathogens were documented, respectively. In 93 of 190 episodes (48.9%), and 84 of 193 episodes (43.5%) there were documented microbiological infections. Fungal infection was documented in very few episodes (6.1 vs. 5.7%).

We also observed a 52.8% prevalence of Gram-positive and a 47.2% prevalence of Gram-negative bacteria in the 2001-2003 period. Observed in the 2004-2005 period were 38.1%Gram-positive and 61.9% Gram-negative bacteria (P=0.012). There was also a significant increase in Pseudomonas aeruginosa prevalence in the second study period (1.9 to 11.6%; P<0.001). Six isolates (31.6%) were discovered to be multiresistant in the 2004-2005 period versus none in the first period. The prevalence of Oxacillin-resistant Staphylococcus was 53.5 and 65.8% in the first and secondperiods, respectively (P=0.23).Conclusion: These documented pathogens are the most commonly observed in febrile neutropenic patients, but the emergence of multidrug-resistantPseudomonas aeruginosa is of some concern.

Potenciais interações medicamentosas em pacientes hospitalizados submetidos à quimoterapia

O estudo visa descrever a incidência de potenciais IM durante todo período de hospitalização de pacientes submetidos à quimioterapia sistêmica, descrever a epidemiologia das associações de medicamentos com potencial IM eidentificar fatores de risco para IMs graves. É um estudo de coorte não controlado. As prescrições de pacientes hospitalizados para tratamento quimioterápico foram prospectivamente avaliadas durante todo o período de internação. Potenciais IMs foramidentificadas através do programa Lexi-Interact e classificadas de acordo a gravidade, evidência científica, mecanismo farmacológico, tempo para início e recomendação de conduta clínica . Resultados: a coorte foi composta por 113 pacientes, que utilizaram em média 8,9 ± 2,7 medicamentos por dia. Todos os pacientes apresentaram pelo menos uma potencial IM, e o número mediano de IMs por paciente foi de 7,0 (P25-P75 : 4,0-12,5). Interações envolvendo antineoplásicos representaram apenas 15% do total de IMs, mas foram identificadas em 75,2% dos pacientes. A maioria das interações foi classificada como de gravidade moderada,7,8% como graves e em 8,4% das IMs havia recomendação de considerar alguma modificação da terapia. Na análise multivariada, o número de medicamentos prescritos (RR para cada medicamento adicional: 1,12; IC 95%: 1,07 – 1,17; P <0,01) e a idade ≥ 60 anos (RR: 1,48;IC 95%:1,03 - 2,14; P <0,01) foram identificados como fatores de risco independentes para IMs graves. Conclusão: Potenciais IMs são muito frequentes em pacientes hospitalizados para tratamento quimioterápico. Pacientes com idade avançada e aqueles em tratamento com elevado número de medicamentos apresentam maior risco de IMs que podem resultar em óbito, hospitalização, dano permanente ou falha terapêutica. Os achados reforçam a importância da adoção de estratégias de vigilância prospectiva para identificação de IMs indesejáveis, visando essencialmente reduzir o risco de toxicidade ou fracasso do tratamento oncológico.