Safety and efficacy of valproic acid preparations.
Safety and efficacy of valproic acid preparations.
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DOI：
10.3233/jrs-150679
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Merculov, V
中科院分区：
文献类型：
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作者：
Pasternak, E;Alyautdin, R;Merculov, V
背景：药物治疗费用的上升是现代医学最显著的负面趋势之一。这一趋势的主要原因是药物开发的临床前和临床阶段的成本增加。专利保护终止后再生产药品的成本要低得多。将原始（参考）药物替换为仿制药将大大降低药物治疗的成本。然而，使用仿制药应该提供与使用原研药相似的药物质量。因此，原研药和仿制药应该是可以互换的，这一因素在很大程度上决定了仿制药的命运。在俄罗斯联邦，药物互换性的概念是由2014年12月22日俄罗斯联邦第429-FZ号联邦法规定的。根据本法规定，可互换药物是指与对照药物经证实具有治疗等效或生物等效性的药物，具有相同的定性和定量组成、有效成分组成、赋形剂组成、相同的剂型和给药途径。特别是互换性问题尤其与治疗作用范围狭窄的药物相关，其中包括一些抗惊厥药[1-3]。目的：利用美国联邦药物不良反应数据库的数据，对丙戊酸制剂治疗组患者的疗效/风险指标进行比较分析。方法：采用Naranjo量表[5]评价本研究中丙戊酸不良反应发生与用药因果关系的确定性程度。这种方法涉及使用问卷，重点是获得具体的答案，以点数为单位进行定量测量。一定数量的点对应一定程度的可靠性。根据对10个问题的回答，在Naranjo量表上，“医学-不”关系的可靠性程度的类别被定义为：确定......9点或更多可能的.....5-8分可能的.....1-4分疑点.....0及以下点在确定因果关系的确定性程度后，只有具有高可靠性报告（确定的、可能的和可能的）的自发报告才进行进一步的分析。结果：联邦药物不良反应数据库包含753例研究期间丙戊酸制剂使用后不良反应发展的自发报告。在753份报告中，216份（29%）包含用另一种药物替代一种药物的信息。药物作用分析表明，在替代原品牌不同药型时，不良反应发生23例（14.6%），而在替代原仿制药时，不良反应发生135例（85.4%）。根据临床情况及不良反应严重程度评估，127例（77%）不良反应严重。不良反应严重程度的判断标准多以临床显著事件和住院时间或住院时间延长为标准。对药品制剂替代不良反应的分布分析显示，158例自发报告中有122例（77%）是由于原药替代仿制药问题引起的。结论：应将仿制药替代原丙戊酸制剂作为药物治疗并发症发生的独立危险因素。在临床实践中，在癫痫控制成功的情况下，应避免替代不同的丙戊酸制剂。
BACKGROUND: Rising of the cost of drug therapy is one of the most notable negative tendencies of modern medicine. The main reasons for this trend are the increased costs for preclinical and clinical phases of drug development. Reproduction of drugs after cessation of patent protection is much less costly. Replacement of the original (reference) drug to generics would greatly reduce the cost of drug therapy. However, the use of generic drugs should provide maintaining quality of medication similar to achieved using the original drug. Thus, the original and generic medicines should be interchangeable and this factor largely determines the fate of the generics. In the Russian Federation the concept of drug interchangeability is entered by the Federal law of Russian Federation № 429-FZ from 22.12.2014. According to this law interchangeable drug is a drug with proven therapeutic equivalence or bioequivalence against the reference drug, having equivalent qualitative and quantitative composition, composition of active ingredients, the composition of excipients, same dosage form and route of administration. Especially the problem of interchangeability is particularly relevant for the drugs with a narrow range of therapeutic action, which include some anticonvulsants [1-3].OBJECTIVE: In this regard the comparative analysis of indicators efficiency/risk using the data from the Federal database of adverse drug reaction in group of the patients treated with preparations of valproic acid is of interest [4].METHODS: Assessment of the degree of certainty of causality between the development of adverse reactions and the use of the drugs of valproic acid in our research was assessed with Naranjo scale [5]. This method involves the use of the questionnaire focused on the obtaining concrete answers that are measured quantitatively in points. A certain number of points correspond to a certain degree of reliability.The category of the degrees of reliability of the relationship "medicine - no" on a scale Naranjo as a result of answers to 10 questions are defined as:the certain......9 and more pointsthe probable.....5-8 pointsthe possible.....1-4 pointsthe doubtful.....0 and less pointsAfter determining the degree of certainty of causality, spontaneous reports only having a high degree of reliability reports (definite, probable and possible) were exposed to the further analysis.RESULTS: The Federal database of adverse drug reaction contains 753 spontaneous reports on the development of adverse reactions after the use of valproic acid preparations during the study period. Among 753 reports, 216 (29%) contained information about replacing one drug with another. The analysis of the action of drugs have shown that on the replacement of different drug forms of the original brand, adverse reactions occurred in 23 cases (14.6%), but on the replacement of the original drug on generic - in 135 (85,4%) cases. On the basis of clinical picture and assessment of severity of adverse reactions it was found that in 127 (77%) cases adverse reactions were serious. The criteria for seriousness of adverse reaction most often were clinically significant event and hospitalization or its prolongation.Analysis of the distribution of adverse reactions on replacement of drug preparations showed that 122 (77%) of 158 spontaneous reports were due to the problems of replacing the original drug to generic.CONCLUSIONS: Thus, replacement of the original preparation of valproic acid with generics should be considered as an independent risk factor for development of complications of drug therapy. In clinical practice, in case of successful seizure control substitutions of different preparations of valproic acid should be avoided.