Potential drug interactions and drug risk during pregnancy and breastfeeding: an observational study in a women's health intensive care unit

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQIntroduction In the pregnancy-puerperal cycle, women may develop complications that require admission to the Intensive Care Unit (ICU). Thus, special attention to pharmacotherapy is necessary, particularly to potential drug interactions (PDIs) and to the396258264FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQsem informaçãosem informaçãoThe researchers would like to thank the multidisciplin ary team of the ICU, the pharmacy staff of the hospital, and the authors, for their support and collaboration during the research. Financial support from student fellowships was provided by Fundaçã

Cost Analysis Of Pharmaceutical Care Provided To Hiv-infected Patients: An Ambispective Controlled Study

Background: Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients. Methods: A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year. Results: Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm3. None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively. Conclusion: This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.231(2008) Secretária de Vigilância em Saúde, Programa Nacional de DST e Aids: Recomendações Para Terapia Anti-retroviral em Adultos Infectados Pelo HIV, , http://www.ensp.fiocruz.br/portal-ensp/judicializacao/pdfs/491.pdf, Brazil, Ministry of HealthDipiro, J., Talbert, R., Yees, G., Matzke, G., Wells, B., Posey, L., (2007) Pharmacotherapy: A Pathophysiologic Approach, , 6th edition. Rio de Janeiro: Mcgraw Hill Companie;Okie, S., Fighting HIV-Lessons from Brazil (2006) N Engl J Med, 354, pp. 1977-1981Ma, A., Chen, D.M., Chau, F.M., Saberi, P., Improving adherence and clinical outcomes through an HIV pharmacist's interventions (2010) AIDS Care, 22, pp. 1189-1194Carcelero, E., Tuset, M., Martin, M., De Lazzari, E., Codina, C., Miró, J., Gatell, J., Evaluation of antiretroviral-related errors and interventions by the clinical pharmacist in hospitalized HIV-infected patients (2011) HIV Med, 12, pp. 494-499Hirsch, J., Gonzales, M., Rosenquist, A., Miller, T., Gilmer, T., Best, B., Antiretroviral therapy adherence, medication use, and health care costs during 3 years of a community pharmacy medication therapy management program for Medi-Cal beneficiaries with HIV/AIDS (2011) J Manag Care Pharm, 17, pp. 213-223March, K., Mak, M.M., Louie, S.G., Effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic (2007) Am J Heal Syst Pharm, 64, pp. 2574-2578Mocroft, A., Youle, M., Moore, A., Sabin, C.A., Madge, S., Lepri, A.C., Tyrer, M., Phillips, A.N., Reasons for modification and discontinuation of antiretrovirals: Results from a single treatment centre (2001) AIDS, 15, pp. 185-194Saberi, P., Dong, B.J., Johnson, M.O., Greenblatt, R.M., Cocohoba, J.M., The impact of HIV clinical pharmacists on HIV treatment outcomes: A systematic review (2012) Patient Prefer Adherence, 6, pp. 297-322Schumock, G.T., Butler, M.G., Meek, P.D., Vermeulen, L.C., Arondekar, B.V., Bauman, J.L., Evidence of the Economic Benefit of Clinical Pharmacy Services: 1996-2000 (2003) Pharmacotherapy, 23, pp. 113-132Bozek, P.S., Perdue, B.E., Bar-Din, M., Weidle, P.J., Effect of pharmacist interventions on medication use and cost in hospitalized patients with or without HIV infection (1998) Am J Health Syst Pharm, 55, pp. 1151-1155Engles-Horton, L.L., Skowronski, C., Mostashari, F., Altice, F.L., Clinical guidelines and pharmacist intervention program for HIV-infected patients requiring granulocyte colony-stimulating factor therapy (1999) Pharmacotherapy, 19, pp. 356-362Horberg, M., Hurley, L., Silverberg, M., Kinsman, C., Quesenberry, C., Effect of clinical pharmacists on utilization of and clinical response to antiretroviral therapy (2007) J Acquir Immune Defic Syndr, 44, pp. 531-539De Rijdt, T., Willems, L., Simoens, S., Economic effects of clinical pharmacy interventions: A literature review (2008) Am J Health Syst Pharm, 65, pp. 1161-1172Areda, C.A., Bonizio, R.C., Freitas, O., Pharmacoeconomy : An indispensable tool for the rationalization of health costs (2011) Braz J Pharm Sci, 47, pp. 231-240Bavinger, C., Bendavid, E., Niehaus, K., Olshen, R.A., Olkin, I., Sundaram, V., Wein, N., Desai, M., Risk of cardiovascular disease from antiretroviral therapy for HIV : A systematic review (2013) PLoS One, 8, p. e59551Dube, M.P., Disorders of glucose metabolism in patients infected with human immunodeficiency virus (2000) Clin Infect Dis, 31, pp. 1467-1475Friis-Møller, N., Sabin, C.A., Weber, R., D'Arminio Monforte, A., El-Sadr, W.M., Reiss, P., Thiébaut, R., Lundgren, J.D., Combination antiretroviral therapy and the risk of myocardial infarction (2003) N Engl J Med, 349, pp. 1993-2003Crum-Cianflone, N., Roediger, M.P., Eberly, L., Headd, M., Marconi, V., Ganesan, A., Weintrob, A., Fraser, S., Infectious Disease Clinical Research Program HIV Working Group, Agan BK: Increasing rates of obesity among HIV-infected persons during the HIV epidemic (2010) PLoS One, 5, p. e10106Strand, L.M., Cipolle, R.J., Morley, P.C., Documenting the clinical pharmacists activities: Back to basics (1988) Drug Intell Clin Pharm, 22, pp. 63-67Pharmacy Workup Notes, , http://www.pharmacy.umn.edu/medmanagenotes/Molino, C.G.R.C., Carnevale, R.C., Rodrigues, A.T., Visacri, M.B., Moriel, P., Mazzola, P.G., Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection (2014) Ther Clin Risk Manag, 10, pp. 631-639SGTAP - Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e OPM Do SUS, , http://sigtap.datasus.gov.br/tabela-unificada/app/sec/inicio.jspRuiz, I., Olry, A., López, M.A., Prada, J.L., Causse, M., Prospective, randomized, two-arm controlled study to evaluate two interventions to improve adherence to antiretroviral therapy in Spain (2010) Enferm Infecc Microbiol Clin, 28, pp. 409-415Martin, S., Wolters, P., Calabrese, S., Toledo-Tamula, M.A., Wood, L.V., Roby, G., Elliott-Desorbo, D.K., The antiretroviral regimen complexity index. A novel method of quantifying regimen complexity (2007) J Acquir Immune Defic Syndr, 45, pp. 535-544Mok, S., Minson, Q., Drug-related problems in hospitalized patients with HIV infection (2008) Am J Health Syst Pharm, 65, pp. 55-59Rastegar, D., Knight, A., Monolakis, J., Antiretroviral medication errors among hospitalized patients with HIV infection (2006) Clin Infect Dis, 43, pp. 933-938Pastakia, S., Corbett, A., Raasch, R., Napravnik, S., Correll, T., Frequency of HIV-related medication errors and associated risk factors in hospitalized patients (2008) Ann Pharmacother, 42, pp. 491-497Misson, J., Clark, W., Kendall, M., Therapeutic advances: Protease inhibitors for the treatment of HIV-1 infection (1997) J Clin Pharm Ther, 22, pp. 109-117Osterberg, L., Blaschke, T., Adherence to medication (2005) N Engl J Med, 353, pp. 487-497Langford, S.E., Ananworanich, J., Cooper, D.A., Predictors of disease progression in HIV infection : A review (2007) Aids Res Ther, 4, pp. 1-14(2012), http://www.aids.gov.br/sites/default/files/anexos/publicacao/2011/50652/boletim_aids_2011_final_m_pdf_26659.pdf, Brazil, Ministry of Health, Secretaria de Vigilancia em Saúde, Departamento de DST Aids e Hepatites Virais: Boletim Epidemiológico - AIDS e DSTMcPherson-Baker, S., Malow, R.M., Penedo, F., Jones, D.L., Schneiderman, N., Klimas, N.G., Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men (2000) AIDS Care, 12, pp. 399-404Shen, J., Sun, Q., Zhou, X., Wei, Y., Qi, Y., Zhu, J., Yan, T., Pharmacist interventions on antibiotic use in inpatients with respiratory tract infections in a Chinese hospital (2011) Int J Clin Pharm, 33 (6), pp. 929-933Yen, Y.-H., Chen, H.-Y., Wuan-Jin, L., Lin, Y.-M., Shen, W.C., Cheng, K.-J., Clinical and economic impact of a pharmacist-managed I.V.-to-P.O. Conversion service for levofloxacin in Taiwan (2012) Int J Clin Pharmacol Ther, 50, pp. 136-141Brennan, T.A., Dollear, T.J., Hu, M., Matlin, O.S., Shrank, W.H., Choudhry, N.K., Grambley, W., An integrated pharmacy-based program improved medication prescription and adherence rates in diabetes patients (2012) Health Aff (Millwood), 31, pp. 120-129Lee, A.J., Boro, M.S., Knapp, K.K., Meier, J.L., Korman, N.E., Clinical and economic outcomes of pharmacist recommendations in a Veterans Affairs medical center (2002) Am J Health Syst Pharm, 59, pp. 2070-2077Janknegt, R., Van Der Meer, J.W.M., Sequential therapy with intravenous and oral cephalosporins (1994) J Antimicrob Chemother, 33, pp. 169-177Preços Máximos de Medicamentos Por Princípio Ativo Para Compras Públicas - Monodrogas/preços Fábrica (PF) e Preço Máximo de Venda Ao Governo (PMVG), , http://portal.anvisa.gov.br/wps/wcm/connect/de29e2004baf729293c5dbbc0f9d5b29/LISTA_CONFORMIDADE_GOV_2012-06-19.pdf?MOD=AJPERES, Accessed July 12, 2014

Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results

Background: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. Methods and results: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/β-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/β-catenin, NF-κβ, and STAT3 signaling pathways. Conclusions: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19

Adverse Drug Reactions And Quality Deviations Monitored By Spontaneous Reports

Objectives: The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods: This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results: A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion: The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases. © 2014 Saudi Pharmaceutical Journal

Nausea, Vomiting And Quality Of Life Of Patients With Cancer Undergoing Antineoplastic Treatment: An Evaluation By Pharmacists

Objective: This study aims to evaluate the frequency and severity of nausea and vomiting using two different instruments and relate them to quality of life (QOL) in patients with cancer receiving antineoplastic treatment. Methods: Severity of chemotherapy-induced nausea and vomiting (CINV) was measured by Common Terminology Criteria for Adverse Events (CTCAE) and a numerical scale. QOL was assessed using the Functional Assessment of Cancer Therapy-General questionnaire. Key findings: Of the 50 patients studied, 60.0% reported nausea (40.0% CTCAE grade 1; 66.7% moderate intensity on numerical scale) and 30.0% reported vomiting (46.7% CTCAE grades 1 and 2, each; 66.7% moderate intensity on numerical scale). CINV did not influence overall QOL. Conclusion: The frequency of CINV was high. There was no association between nausea/vomiting and overall QOL

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters

What is known and objective Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Methods Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. Results and discussion There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2·7 times more hydrolysed cisplatin than brand A. What is new and conclusion The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations. Some cases of hypersensitivity that appeared to be associated with the brand of cisplatin used were observed. Increases in the hydrolyzed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients.4014147Rosenberg, B., Van Camp, L., Krigas, T., Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode (1965) Nature, 205, pp. 698-699Rosenberg, B., Van Camp, L., Trosko, J.E., Mansour, V.H., Platinum compounds: A new class of potent antitumour agents (1969) Nature, 222, pp. 385-386Reed, E., Cisplatin and its Analogs (2005) DeVita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology, p. 339. , De Vita V.T. Hellman S. Rosenberg S.A. eds. Philadelphia, PA: Lippincott Williams & WilkinsRabik, C.A., Dolan, M.E., Molecular mechanisms of resistance and toxicity associated with platinating agents (2007) Cancer Treat Rev, 33, pp. 9-23Weiss, R.B., Bruno, S., Hypersensitivity reactions to cancer chemotherapeutic agents (1981) Ann Int Med, 94, pp. 66-72Zweizig, S., Roman, L.D., Muderspach, L.I., Death from anaphylaxis to cisplatin: A case report (1994) Gynecol Oncol, 53, pp. 121-122Shlebak, A.A., Clark, P.I., Green, J.A., Hypersensitivity and cross-reactivity to cisplatin and analogues (1995) Cancer Chemother Pharmacol, 35, pp. 349-351Randall, J.M., Bharne, A.A., Bazhenova, L.A., Hypersensitivity reactions to carboplatin and cisplatin in non-small cell lung cancer (2013) J Thorac Dis, 5, pp. E53-E57Sakaeda, T., Kadoyama, K., Yabuuchi, H., Niijima, S., Seki, K., Shiraishi, Y., Okuno, Y., Platinum agent-induced hypersensitivity reactions: Data mining of the public version of the FDA Event Reporting System, AERS (2011) Int J Med Sci, 8, pp. 332-338Görög, S., Drug safety, drug quality, drug analysis (2008) J Pharm Biomed Anal, 48, pp. 247-253Bannister, S.J., Sternson, L.A., Repta, A.J., Urine analysis of platinum Species derived from cis-D1-chlorodiammineplatinum(II) by high-performance liquid chromatography following derivatization with sodium diethyldithiocarbamate (1979) J Chromatogr, 173, pp. 333-342Lopes-Flores, A., Jurado, R., Garcia-Lopes, P., A high-performance liquid chromatographic assay for determination os cisplatin in plasma, cancer cell, and tumor samples (2005) J Pharmacol Toxicol Methods, 52, pp. 366-372USP, (2013) USP29- NF24. Water, Method, p. 521. , Rockville, MD: US Pharmacopeial ConventionHunter, D., Milton, R., Perry, K.M.A., Asthma caused by complex salts of platinum (1945) Br J Ind Med, 2, pp. 92-98Saunders, M.P., Denton, C.P., O'Brien, M.E.R., Blake, P., Gore, M., Wiltshaw, E., Hypersensitivity reactions to cisplatin and carboplatin - A report on six cases (1992) Ann Oncol, 3, pp. 574-576Vogel, W.H., Infusion reactions: Diagnosis, assessment, and management (2010) Clin J Oncol Nurs, 14, pp. E10-E21Lenz, H.J., Management and preparedness for infusion and hypersensitivity reactions (2007) Oncologist, 12, pp. 601-609Goldberg, A., Altaras, M.M., Mekori, Y.A., Beyth, Y., Confino-Cohen, R., Anaphylaxis to cisplatin: Diagnosis and value of pretreatment in prevention of recurrent allergic reactions (1994) Ann Allergy, 73, pp. 271-272Bosch, M.E., Sánchez, A.J.R., Rojas, F.S., Ojeda, C.B., Analytical methodologies for the determination of cisplatin (2008) J Pharmacol Biomed Anal, 47, pp. 451-459Miller, R.P., Tadagavadi, R.K., Ramesh, G., Reeves, W.B., Mechanisms of cisplatin nephrotoxicity (2010) Toxins, 2, pp. 2490-2518Lippard, S.J., Chemistry and molecular biology of platinum anticancer drugs (1987) Pure Appl Chem, 59, pp. 731-742Makrilia, N., Syrigou, E., Kaklamanos, I., Manolopoulos, L., Saif, M.W., Hypersensitivity reactions associated with platinum antineoplastic agents: A systematic review (2010) Met-Based Drugs, 2010, p. 11Harford, C., Sarkar, B., Studies of induction of metallothionein in Jar (human choriocarcinoma) cells by cis and trans isomers of diamminedichloroplatinum (II) and their hydrolyzed species (1989) Mol Toxicol, 2, pp. 67-7