Abstract:
PURPOSE:Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands. METHODS:Through methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1-year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in-depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products. FINDINGS:Reporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93-22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and premature loss of efficacy (shorter duration of action) was described in 98 cases (42.6%) and occurred primarily in the afternoon. Impacts on social functioning, such as disruption in work or school performance or adverse social behaviors, were found in 51 cases (22.2%). IMPLICATIONS:The ~10-fold higher reporting rate of therapeutic failure with the generic product relative to its reference product in the present Canadian study resembles findings with US-marketed generic products. While these results should be interpreted with caution due to the limitations of spontaneous adverse event reporting, which may confound comparisons across products, similar findings nonetheless led the US Food and Drug Administration to declare in 2014 that 2 methylphenidate ER generic products in the United States were neither bioequivalent nor interchangeable with OROS methylphenidate-their reference product. Our results indicate a potential safety issue with the Canadian-marketed generic and suggest a need for further investigation by Health Canada.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Park-Wyllie L,van Stralen J,Castillon G,Sherman SE,Almagor Ddoi
10.1016/j.clinthera.2017.08.018subject
Has Abstractpub_date
2017-10-01 00:00:00pages
2006-2023issue
10eissn
0149-2918issn
1879-114Xpii
S0149-2918(17)30939-6journal_volume
39pub_type
杂志文章abstract:BACKGROUND:Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). OBJECTIVES:The objective of this study was to assess health care utilization and expenditures associated with tre...
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doi:10.1016/j.clinthera.2011.05.049
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abstract:BACKGROUND:Poor glycemic control in hospitalized patients has been associated with increased morbidity and mortality. Research suggests that analogue bolus insulin may be more effective in achieving blood glucose (BG) control compared with human bolus insulin. OBJECTIVE:This study compares mortality, length of stay (L...
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journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
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abstract:OBJECTIVE:The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mell...
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abstract::Neisseria microorganisms (Neisseria lactamica, Neisseria sicca, and Neisseria mucosa) are regarded as normal respiratory commensals. Branhamella catarrhalis (formerly Neisseria catarrhalis) has also been regarded as a normal respiratory commensal, but reports indicate that it can be pathogenic. The role of Neisseria s...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::We studied the effects of atropine and pirenzepine on acid secretion induced by electrical vagal stimulation (EVS) and on healing of gastric ulcers after mucosal excision in rats. Both atropine (50, 125, and 250 micrograms/kg/hr) and pirenzepine (2.5, 5.0, and 12.5 mg/kg/hr), administered intraperitoneally, inhibited ...
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pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Hypoglycemia in people with insulin-treated type 2 diabetes can be a limiting factor for management and a barrier to optimizing glycemic control. Even mild episodes of hypoglycemia can affect an individual's quality of life, and fear of hypoglycemia can lead to underinsulinization. This article explores the prevalence...
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pub_type: 杂志文章,评审
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abstract:BACKGROUND:Outcomes in patients with type 2 diabetes mellitus (DM) can differ based on the antidiabetic medication that is used. Thiazolidinediones (TZDs) are a newer class of agents used for the treatment of type 2 DM. No previous study has compared health care utilization associated with the 2 TZDs on the market. OB...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Healing rates were examined retrospectively in 124 outpatients with peptic ulcer who had received cimetidine for at least four weeks. Treatment was unsuccessful in 73 patients. A statistical analysis of the factors involved in treatment failure revealed that in patients with duodenal ulcers 60.6% of the treatment succ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
abstract:PURPOSE:Stroke is the second leading cause of death and the third leading cause of disability worldwide. Diabetes mellitus and the associated hyperglycemia are important risk factors for acute ischemic stroke and are associated with poor prognosis. Neurovascular protection is an important therapeutic target to achieve ...
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pub_type: 杂志文章,评审
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更新日期:2020-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86736-3
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abstract:BACKGROUND:Diabetes mellitus (DM) is a powerful independent risk factor for multivessel, diffuse coronary artery disease (CAD). The optimal coronary revascularization strategy in DM is not clearly defined, but past trials have suggested an advantage for coronary artery bypass grafting (CABG). Recently, the Future Revas...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2013.07.427
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:NSAIDs are associated with risks of gastrointestinal (GI) and cardiovascular (CV) toxicities. It has been reported that the risks of GI and CV events are dose related, resulting in guidance explicitly emphasizing the use of NSAIDs at the lowest effective dose for the shortest duration. To understand the pote...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2014.04.012
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:These studies assessed the comparative efficacy of rofecoxib and valdecoxib in the treatment of acute postoperative dental pain. METHODS:Two randomized, double-blind, placebo-controlled, single-dose studies were conducted in patients undergoing extraction of > or =2 third molars, with > or =1 mandibular impa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2006.07.005
更新日期:2006-07-01 00:00:00
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更新日期:2016-01-01 00:00:00
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更新日期:2009-09-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2013-10-01 00:00:00
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journal_title:Clinical therapeutics
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更新日期:1998-01-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2001-04-01 00:00:00
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doi:10.1016/j.clinthera.2018.03.016
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:Moxifloxacin is a fluoroquinolone antimicrobial agent with proven efficacy against community-acquired respiratory pathogens. Common adverse effects associated with its use include gastro-intestinal symptoms, but nephrotoxicity has not yet been reported to the manufacturer or in the literature (based on a MED...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.08.008
更新日期:2005-08-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.12.014
更新日期:2009-12-01 00:00:00
abstract::One hundred sixteen children between 2 and 15 years of age entered a clinical trial of albendazole after examination of their stools revealed ova of one or more intestinal helminths. The drug was administered as a single 400-mg dose (20 ml of 2% suspension) to all the patients except those having Hymenolepis nana infe...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:The aim of this research letter was to describe the use of N-carbamoyl-L-glutamate as first-line treatment of hyperammonemia in a 4-month-old female patient with propionic acidemia (PA). METHODS:A 4-month-old female patient weighing 3.9 kg presented with decompensation with PA and initial hyperammonemia of 4...
journal_title:Clinical therapeutics
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doi:10.1016/j.clinthera.2010.04.004
更新日期:2010-04-01 00:00:00
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更新日期:2019-06-01 00:00:00