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INTRODUCTION: Professional conferences are where research findings are initially presented. Studies suggest many research ideas presented at conferences are never published. Previous studies have demonstrated that the full publication rate of abstracts presented at pharmacy meetings is approximately 20%. The objective of this study was to determine the full publication rate of hematology/oncology abstracts presented at major pharmacy organization annual meetings. METHODS: A systematic search of PubMed and Google Scholar was performed. Publication status was evaluated for hematology/oncology abstracts presented at annual meetings for the following organizations: American College of Clinical Pharmacy Annual Meeting, American Society of Health-System Pharmacists Midyear Clinical Meeting, Hematology/Oncology Pharmacy Association Annual Meeting, and International Society of Oncology Pharmacy Practitioners Annual Meeting. Data collected included the meeting of abstract presentation, number of authors, abstract study type, country of origin, journal of publication, and type of publication. Abstracts presented as trainee research were excluded. RESULTS: Of 451 oncology abstracts evaluated, the most common topic categories included pharmacotherapy (n = 244; 54.1%), clinical pharmacy practice (n = 84; 18.6%), and operational/compounding (n = 69; 15.3%). The overall publication rate was 17.5% (n = 79). Abstracts were published as full manuscripts over a spread of 48 different journals. Factors associated with full publication included abstracts with more than 5 authors (OR 3.86, 95% CI 2.32-6.43; p < 0.0001) and abstracts presented at oncology-focused pharmacy meetings (OR 2.92, 95% CI 1.49-5.72; p = 0.0018). CONCLUSION: This study showed an overall publication rate of 17.5% for abstracts presented at pharmacy meetings, consistent with prior studies.
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Objective: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. Data Sources: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. Study Selection and Data Extraction: Article bibliographies and drug interaction databases were reviewed. Search terms included HIV, antiretroviral therapy, antineoplastic agents, malignancies, and drug interactions. Data Synthesis: In the pre-antiretroviral therapy (ART) era, malignancies in PLWH were AIDS-defining illnesses, and life expectancy was shorter. Nowadays, PLWH are living longer and developing malignancies, including lung, anal, and prostate cancers. Concurrently, the oncology landscape has evolved, with novel oral targeted agents and immunotherapies becoming routine elements of care. The increased need for and complexity with antineoplastics in PLWH has led to recommendations for multidisciplinary care of this unique population. Evaluation of DDIs requires review of metabolic pathways, absorption mechanisms, and various drug transporters associated with antineoplastics and ART. Relevance to Patient Care and Clinical Practice: This review summarizes available data of non-AIDS-defining malignancies, principles of HIV care in the patient with malignancy, and guidance for assessing DDIs between antineoplastics and ART. Summary DDI tables provide point-of-care recommendations. Conclusions: The availability of ART has transformed AIDS into a chronic medical condition, and PLWH are experiencing age-related malignancies. Pharmacists play an important role in the management of this patient population.
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Antirretrovirais/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Conduta do Tratamento Medicamentoso/organização & administração , Neoplasias/tratamento farmacológico , Antirretrovirais/administração & dosagem , Antirretrovirais/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Interações Medicamentosas , Feminino , Infecções por HIV/complicações , Humanos , Imunoterapia/métodos , Masculino , Neoplasias/complicaçõesRESUMO
Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.
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Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sulfonamidas/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Neutropenia/induzido quimicamente , Síndrome de Lise Tumoral/etiologiaRESUMO
Febrile neutropenia (FN) is an oncological emergency and serious complication often resulting from chemotherapy. In patients with a weak or completely suppressed immune system, a fever may be the only sign of an underlying infection and immediate treatment is needed. Using risk evaluation scores, it is possible to stratify individual patient degree of risk. However, all patients warrant immediate antibiotic coverage. Antibiotic treatment of FN is broadened or narrowed based on individualized clinical scenarios. Prophylactic antimicrobials may be used in specific high-risk situations. This article briefly reviews FN, describes risk assessment tools, and discusses treatment and prophylactic options.
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The authors present the clinical outcomes and therapeutic application of newly approved pharmacotherapies for chronic lymphocytic leukemia and highlight emerging investigational therapeutic options.
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The American Diabetes Association recommends insulin initiation when A1c ≥10%. The aim of this study was to determine adherence to insulin initiation in patients with an A1c ≥10% at an outpatient family medicine clinic. The secondary objectives were to determine whether initiation of insulin within 3 weeks of an A1c ≥10% increased the rate or decreased the time to achieve an A1c <7% and to determine whether pharmacist involvement increased the rate of reaching an A1c <7%. This institutional review board-approved, retrospective, observational, cohort study identified 120 patients with type 2 diabetes mellitus and an A1c ≥10% in 2014. Patients already receiving insulin or those without a follow-up A1c were excluded. Study outcomes included proportion of patients receiving insulin therapy within 3 weeks of A1c >/=10%, rate of meeting A1c <7%, time to reach A1c <7%, and proportion of patients meeting with a pharmacist. Fifty-five patients with a mean age of 55 years, a mean duration of diabetes of 6.4 years, and a mean baseline A1c of 11.7% met the inclusion criteria. Most patients were receiving no therapy (29%), monotherapy (27%), or dual therapy (29%) at baseline. Insulin was initiated in 5 patients (9.1%, P < 0.05) within 3 weeks of the qualifying A1c. Another 5 patients (P < 0.05) received insulin at some point during the study. An A1c <7% was achieved in 35.6% of patients not receiving insulin, 20% of patients receiving early insulin, and no patients who received insulin after 3 weeks. The mean time to A1c <7% was 6 months for patients not on insulin and 3 months for those receiving early insulin. Thirty-three percent of patients who met with a pharmacist reached an A1c <7% compared with 30% of patients who did not. Adherence to insulin initiation guidelines and rate of achieving A1c <7% in patients with A1c ≥10% is low. Increasing pharmacy involvement may increase the rate of reaching goal A1c.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Guias de Prática Clínica como Assunto , Adulto , Idoso , Assistência Ambulatorial/normas , Estudos de Coortes , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Farmacêutica/organização & administração , Farmacêuticos/organização & administração , Projetos Piloto , Papel Profissional , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Hyponatremia is a common electrolyte disorder and is associated with multiple comorbidities. Management strategies are varied and etiology-dependent. The use of tolvaptan, a vasopressin antagonist, outside of clinical trials has not been well characterized. OBJECTIVES: To quantify tolvaptan compliance with institutional guidelines and make recommendations concerning reasonable expectations for its role in hyponatremia management. METHODS: This was a retrospective observational study in a 125-bed community hospital. Patients admitted in 2013 who received at least one dose of tolvaptan were included. RESULTS: Thirty-seven patient encounters were evaluated. Tolvaptan was prescribed with 83.7% adherence to the institutional order set. Mean age was 71 ± 16.4 years with 20 (54%) females. Hyponatremia was a contributory cause of admission in 15 (40.5%) patients and offending medications were discontinued in 7 (19%). Causes of hyponatremia included syndrome of inappropriate antidiuretic hormone (SIADH), heart failure, and cirrhosis in 78.3%, 8.2%, and 13.5% of participants, respectively. Management included fluid restriction in 19 (51%) and furosemide in 5 (13.5%), with tolvaptan administration on average 3.2 days after admission. Most patients (78.4%) required ≤2 doses. Sodium concentration was elevated 8 mEq/L by the end of hospitalization. Discharge to palliative care or death occurred in 8 (21.6%). Postdischarge review revealed 3 (8%) maintained sodium concentration ≥130 mEq/dL. CONCLUSION: Tolvaptan was initiated after other interventions and with limited duration per institutional guidelines. This cohort had complicating underlying chronic diseases. These results will be used to refine recommendations with pharmacist input for risk/benefit stratification based on reasonable expectations.
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OBJECTIVE: To review the literature evaluating the benefit and tolerability of aromatase inhibitors (AIs) in breast cancer risk reduction. DATA SOURCE: A PubMed search (1966-July 2014) was conducted using the key terms breast cancer risk reduction, with anastrozole, exemestane, or letrozole, or aromatase inhibitors. Abstracts from recent breast cancer symposia were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles were reviewed for inclusion. The references of articles were reviewed for additional studies. The review focused on AI trials in women without preexisting cancer; review articles, preclinical studies, and studies of AI use in early-stage cancer were excluded. DATA SYNTHESIS: Lifestyle modifications, surgery, and selective estrogen receptor modulators (SERMs) are options for women at high risk for breast cancer compared with the general population. Statements published by various organizations help guide appropriate patient selection. Toxicities with SERMs, including increased risk for endometrial cancer, thromboembolic events, and cataracts, have limited their utility. AIs inhibit the endogenous production of estrogen and are mechanistically distinct from SERMs. Placebo-controlled trials with exemestane and anastrozole in postmenopausal women with breast cancer risk factors demonstrated at least 50% efficacy in invasive breast cancer reduction and were well tolerated. Vasomotor symptoms were experienced, but no differences in fractures or cardiovascular events were observed. SUMMARY: Exemestane and anastrozole appear to offer benefit for postmenopausal woman at high risk for invasive breast cancer and are well tolerated. AIs offer an alternative for high-risk postmenopausal women desiring chemoprevention but with SERM contraindications. More trials are warranted to help further guide appropriate patient selection.
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Anticarcinógenos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Anastrozol , Androstadienos/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Letrozol , Invasividade Neoplásica , Nitrilas/uso terapêutico , Pós-Menopausa , Risco , Triazóis/uso terapêuticoRESUMO
OBJECTIVE: To describe primarily implicit instruments for assessing medication use in older adults. DATA SOURCES: Literature was identified via PubMed (1966-2014) and Google Scholar using the following search terms: geriatric/medication use, implicit criteria, inappropriate medication use, inappropriate prescribing, older adults/medication use, and polypharmacy. Reference citations from identified publications were also reviewed. STUDY SELECTION: All articles in English identified from data sources were evaluated. Instruments applicable to pharmacy and multiple medication classes were included. We excluded instruments developed for a single medication or medication class, for a single condition or disease state, as primarily an academic instrument, using primarily explicit criteria, for use primarily by health care practitioners other than pharmacists, or for regulatory purposes. DATA SYNTHESIS: Seven instruments were reviewed by evaluating characteristics, components of prescribing and medication use addressed, and settings in which they have been evaluated and validated. Screening Medications in the Older Drug User (SMOG) is a six-question instrument developed specifically for community pharmacists. The Medication Appropriateness Index (MAI); Assess, Review, Minimize, Optimize, Reassess (ARMOR) tool; and Tool to Improve Medications in the Elderly via Review (TIMER) are more comprehensive instruments, but they require clinical judgment and are time intensive. Assessing Care of Vulnerable Elders-3 (ACOVE-3) and the Good Palliative-Geriatric Practice Algorithm (GPGPA) are useful in determining need for medication continuation in older adults who are closer to the end of life. The Assessment of Underutilization (AOU) is an implicit tool to guide medication initiation. CONCLUSION: Each instrument is unique in design, which may be beneficial in some pharmacy practice settings and present barriers in others. The use of multiple instruments may be necessary to optimize therapy in this vulnerable patient population.
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Prescrição Inadequada/estatística & dados numéricos , Padrões de Prática Médica/normas , Medicamentos sob Prescrição/uso terapêutico , Idoso , Algoritmos , Humanos , Assistência Farmacêutica/organização & administração , Farmacêuticos/organização & administração , PolimedicaçãoAssuntos
Hepatomegalia/induzido quimicamente , Mitragyna/efeitos adversos , Adulto , Humanos , Masculino , Adulto JovemAssuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Inibidores Enzimáticos/efeitos adversos , Humanos , MasculinoRESUMO
OBJECTIVE: To review the clinical trials, pharmacologic characteristics, safety, and efficacy of the elvitegravir/cobicistat/emtricitabine/tenofovir single tablet formulation (Stribild). DATA SOURCES: Literature searches were performed in MEDLINE (1948-September 2012) and PubMed (1966-September 2012) using the search terms GS-9137, elvitegravir, GS 9350, cobicistat, quad pill, Stribild, and integrase inhibitors. Abstracts from HIV/AIDS conferences were reviewed. STUDY SELECTION AND DATA EXTRACTION: Phase 3 studies evaluating the safety and efficacy of Stribild were preferentially evaluated, as well as relevant references from the published studies. DATA SYNTHESIS: Stribild contains complete antiretroviral therapy for HIV-1 infection in a single tablet. It is the first once-daily therapy option available with an integrase inhibitor and a novel pharmacokinetic boosting agent. Stribild has shown noninferiority in viral load suppression at 48 weeks when compared with dual nucleoside/nucleotide reverse transcriptase inhibitor and either a ritonavir-boosted protease inhibitor or nonnucleoside reverse transcriptase inhibitor regimen. Stribild was well tolerated, but some patients experienced increases in serum creatinine early in treatment that stabilized over time. CONCLUSIONS: Stribild is the first single-tablet regimen for HIV-1 infection treatment containing an integrase inhibitor. It is expected to have a prominent place in the formularies of health plans providing care for individuals with HIV-1 infection.
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Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Carbamatos/uso terapêutico , Desoxicitidina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Quinolonas/uso terapêutico , Tiazóis/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Humanos , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Comprimidos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Carga Viral/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection. DATA SOURCES: Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome. Additional publications were obtained through review of references within primary literature publications as well as pertinent Web sites. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated and all pertinent information was included. All studies relevant to the evaluation of efficacy and safety of tesamorelin in the management of HIV-associated lipodystrophy were included, with a focus on trials completed in humans. DATA SYNTHESIS: In 2 Phase 3 clinical trials and their pooled analyses, tesamorelin was proven to significantly decrease waist circumference and visceral adipose tissue (VAT) following 26 weeks of treatment. Both trials also demonstrated significant improvements in some subjective body image parameters. Both studies had 26-week extension phases that confirmed maintenance of VAT improvements on treatment without adverse impact on blood glucose and lipid parameters. Limited data support off-label uses of tesamorelin at this time. CONCLUSIONS: Tesamorelin is effective in improving visceral adiposity and body image in patients with HIV-associated lipodystrophy over 26-52 weeks of treatment. Potential limitations for its use include high cost and lack of long-term safety and adherence data. Tesamorelin provides a useful treatment option for management of patients with significant lipodystrophy related to HIV infection.
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Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Animais , Custos de Medicamentos , Hormônio Liberador de Hormônio do Crescimento/economia , Hormônio Liberador de Hormônio do Crescimento/farmacocinética , Hormônio Liberador de Hormônio do Crescimento/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/economia , Humanos , Uso Off-LabelRESUMO
BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality for people with type 2 diabetes mellitus (T2DM). Previous pharmacological management recommendations focused primarily on glucose lowering. However, new data demonstrate that select glucagon-like peptide 1 receptor agonists (GLP1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) not only provide glucose lowering but also can reduce the risk of cardiovascular (CV) disease. OBJECTIVES: The purpose of this study was to evaluate the current data regarding CV benefits of GLP1 RA and SGLT2i in select patients with T2DM and the impact on clinical guidelines so that nurse practitioners may optimize pharmacologic management of patients with T2DM. DATA SOURCES: A literature review was conducted using the PubMed and CINAHL complete databases to identify studies with CV benefits of GLP1 RA and SGLT2i. Pivotal clinical trials were selected for review. CONCLUSIONS: Select GLP1 RA and SGLT2i can reduce the risk of major adverse CV events, death from CV cases, or hospitalization due to heart failure (HF) in patients with a history of, or at high risk for, CV disease. IMPLICATIONS FOR PRACTICE: Based on data from major CV outcomes trials, clinical guidelines recommend GLP1a or SGLT2i in select patients for glucose lowering and CV risk reduction. In addition, even in patients who have achieved glycemic goals, these agents can provide additional benefit by reducing the incidence of major CV adverse events or hospitalization for HF. Understanding the data will help nurse practitioners select the most appropriate agent for a given individual based on comorbidities.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Glucose , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGROUND: Glucommander™ (GM), an electronic glycemic management system, was implemented across a multi-hospital health system as the standard of care for glycemic control. GM provides insulin dosing recommendations based on patient-specific blood glucose (BG) trends after providers select either a custom dose or weight-based multiplier as the initial dosing strategy for the first 24 hours. This study evaluated the impact of initial subcutaneous (SC) GM insulin dosing strategies on glycemic management. METHODS: Non-intensive care unit patients treated with SC GM using either initial custom (based on provider discretion) or weight-based multiplier settings (0.3, 0.5, or 0.7 units/kg/day) were evaluated in this retrospective chart review. The primary endpoint was time to target BG range defined as time to first two consecutive in range point of care BG. Secondary endpoints included percentage of BG values in target range, percentage of orders following institutional recommendations, length of stay (LOS), average BG, and incidence of hypoglycemia and hyperglycemia. RESULTS: A review of 348 patients showed time to target BG was not significantly different between custom and multiplier groups (55 vs 64 hours, P = .07). Target BG was achieved in less than half of patients in both groups (47% vs 44%, respectively). There were no differences in hospital LOS, proportion of BG in target range, rates of hypo/hyperglycemia, and average BG. CONCLUSIONS: Custom initial SC GM insulin dosing settings showed a nonsignificant decrease in time to target BG range compared to pre-defined multiplier settings. Future studies evaluating the impact of compliance with institutional recommendations on BG control are warranted.
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Glicemia , Hipoglicemiantes , Algoritmos , Humanos , Insulina , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the efficacy and tolerability of combination glucagon-like peptide-1 (GLP-1) analogs and insulin in the management of type 2 diabetes mellitus (T2DM) in adults. DATA SOURCE: A MEDLINE search (1966-April 2010) was conducted using the key terms glucagon-like peptide-1 analog, exenatide, incretin mimetic, liraglutide, diabetes mellitus, and insulin. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data source were evaluated and reviewed for inclusion. Original research and retrospective cohorts were included in this review. The references of articles that we identified were examined for any additional studies appropriate for review. DATA SYNTHESIS: Exenatide is a subcutaneously administered GLP-1 receptor agonist that is used for the improvement of glycemic control in adults with T2DM. Through actions similar to those of endogenous GLP-1, exenatide contributes to improved postprandial glycemic control and weight loss. The concomitant use of exenatide and insulin is currently not Food and Drug Administration-approved due to lack of clinical trial data. However, combination insulin and exenatide may be advantageous, especially for reducing weight gain, particularly for obese patients with T2DM. Several small prospective and retrospective studies evaluating combination therapy found statistically significant reductions in hemoglobin A(1c) (A1C), weight, and total daily insulin dose requirements. The most common adverse effects reported included gastrointestinal effects, such as nausea and vomiting, and hypoglycemia. CONCLUSIONS: Although there is a limited amount of data and not all studies demonstrated A1C reduction, the combination of exenatide with insulin therapy appears to be a safe option in the management of T2DM. It may be a promising therapeutic strategy for some patients, as reductions in weight and insulin doses were observed. Further well-designed prospective trials are warranted to fully determine the long-term effectiveness and safety of this combination as well as its place in therapy.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Insulina/efeitos adversos , Insulina/farmacologia , Insulina/uso terapêutico , Peptídeos/efeitos adversos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Receptores de Glucagon/agonistas , Peçonhas/efeitos adversos , Peçonhas/farmacologia , Peçonhas/uso terapêuticoAssuntos
Baclofeno/efeitos adversos , Agonistas dos Receptores de GABA-B/efeitos adversos , Síndromes Neurotóxicas/etiologia , Insuficiência Renal Crônica/complicações , Acidentes por Quedas , Idoso de 80 Anos ou mais , Confusão/induzido quimicamente , Confusão/diagnóstico , Confusão/psicologia , Erros de Diagnóstico , Eletroencefalografia , Feminino , Humanos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral/diagnósticoRESUMO
OBJECTIVE: To review pharmacologic, pharmacokinetic, efficacy, and safety data for fesoterodine and determine its role in the treatment of overactive bladder. DATA SOURCES: A MEDLINE search (1966-July 2009) was conducted using the key words fesoterodine, tolterodine, muscarinic receptor antagonist, anticholinergic, overactive bladder, urge incontinence, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, and receptor binding. STUDY SELECTION AND DATA EXTRACTION: All articles written in English that were identified from the data sources were evaluated, prioritizing randomized, controlled trials with human data. The references of published articles that we identified were examined for any additional studies appropriate for the review. DATA SYNTHESIS: Fesoterodine, a competitive muscarinic receptor antagonist, is converted to its active metabolite, 5-hydroxymethyltolterodine, by nonspecific esterases, bypassing the cytochrome P450 system. Two randomized controlled Phase 3 trials examined the safety and efficacy of fesoterodine in the treatment of overactive bladder. Fesoterodine was found to produce significant improvements in the treatment of overactive bladder symptoms compared with placebo. Post hoc analysis of these trials demonstrated significant improvements in health-related quality of life in patients with overactive bladder. Only one study included tolterodine, and direct comparisons between fesoterodine and tolterodine were not conducted. The most common treatment-emergent adverse effects associated with fesoterodine included dry mouth, constipation, urinary tract infection, and headache. CONCLUSIONS: Fesoterodine appears to be effective and generally safe for the treatment of overactive bladder. The efficacy and safety of fesoterodine in overactive bladder treatment seem to be at least similar to that of tolterodine. Although additional comparative trials are needed, based on available data, it does not appear that fesoterodine provides a substantial advantage over extended-release tolterodine in either efficacy or safety.
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Compostos Benzidrílicos/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Animais , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Cresóis/efeitos adversos , Cresóis/uso terapêutico , Humanos , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacologia , Fenilpropanolamina/efeitos adversos , Fenilpropanolamina/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tartarato de Tolterodina , Bexiga Urinária Hiperativa/fisiopatologiaRESUMO
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC. Alectinib is a next-generation ALK inhibitor initially approved by the Food and Drug Administration for use in patients with metastatic ALK-positive NSCLC who are intolerant of or have disease progression during crizotinib therapy. In clinical trials, alectinib was found effective for delaying disease progression and, more importantly, reducing brain metastases in patients with NSCLC who developed resistance or intolerance to previous crizotinib therapy. Published data from clinical trials indicate that the most common grade 1 and 2 adverse effects associated with alectinib use are fatigue, constipation, peripheral edema, and myalgia; the most common grade 3 or 4 reactions include increases in creatine phosphokinase, alanine aminotransferase, and aspartate aminotransferase levels. CONCLUSION: Alectinib appears to be effective and safe for use in patients with metastatic ALK-positive NSCLC, with demonstrated superiority over crizotinib in terms of PFS rates. Research to better define ALK inhibitor resistance mechanisms and alectinib's place in therapy is ongoing.
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Carbazóis/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piperidinas/administração & dosagem , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Carbazóis/efeitos adversos , Carbazóis/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologiaRESUMO
For diabetes mellitus patients who require higher doses of insulin, pen-delivered concentrated insulins offer smaller volumes and potentially a lower risk of dosing errors.