Bajcetic Milica, Kearns Gregory L, Jovanovic Ida, Brajovic Milan, van den Anker John N
Department of Pharmacology, School of Medicine, University of Belgrade, P.O. Box 38, 11129 Belgrade 102, Serbia.
Curr Pharm Des. 2015;21(39):5668-73. doi: 10.2174/1381612821666150901105925.
The paucity of marketed drug products that have been adequately studied in infants and children and subsequently, licensed (or labeled) for pediatric use has caused abundant use of off-label and unauthorized products in this patient population. In those instances where insufficient pharmacologic or therapeutic information exists for children, the potential for off-label use of medicines to result in therapeutic misadventure does as well. In the USA, a series of regulatory measures have been introduced since 1997 which have increased both the number and scope of pediatric drug trials and also, fostered the development of ageappropriate drug formulations by pharmaceutical companies. Provisions of these regulations for previously marketed drugs include the potential for a company to be granted 6 months of marketing exclusivity, thereby providing them with a financial incentive. For new drugs being developed that have potential pediatric use, the regulations mandate the inclusion of children in the drug development process. In the EU comparable measures have been very recently (Jan 2007) signed into European law to overcome the therapeutic orphan status of the infants and children of Europe.
The aims of this study was to compare the availability of age-appropriate oral formulations labeled for use in children less than 12 years of age in Serbia, Germany and USA in 2007, and to investigate if certain drug groups of therapeutic importance to children had fewer medicines appropriately labeled for pediatric patients available. The primary sources of information for determining the ageappropriate oral dosage forms, and their licensing and labeling status were the official manuals on drug information and national formularies in 2007.
The general availability of oral drugs was the highest in the USA (304), followed by Germany (235) and Serbia (156). From all these oral drugs the availability of labeled age-appropriate pediatric dosage formulations was only between 21.2% and 47.7%. Moreover, there were striking differences between the three countries in the availability of labeled age-appropriate formulations for certain drug groups such as cardiovascular (absent in Serbia) and antiparasitic drugs (absent in Serbia and Germany).
Our data suggest that significant country-to-country differences continue to exist in both the number and type of oral drug formulations that have pediatric labeling. Potential contributing factors include country-specific differences in the drug regulatory process, capacity for pharmaceutical development and the regulatory lag time associated with the implementation of drug regulation specifically addressing pediatric product development and labeling. We hypothesize that the new European regulation concerning medicines and children will improve the current unacceptable situation.
在婴儿和儿童中得到充分研究并随后获得儿科使用许可（或标签）的上市药品数量稀少，导致该患者群体中大量使用未标注适应症和未经授权的产品。在儿童缺乏足够药理或治疗信息的情况下，药品的未标注适应症使用也有可能导致治疗失误。在美国，自1997年以来出台了一系列监管措施，这些措施增加了儿科药物试验的数量和范围，也促进了制药公司开发适合儿童年龄的药物剂型。这些法规对先前上市药物的规定包括公司有可能获得6个月的市场独占权，从而为它们提供经济激励。对于正在开发的有潜在儿科用途的新药，法规要求在药物开发过程中纳入儿童。在欧盟，最近（2007年1月）签署了类似措施并将其纳入欧洲法律，以克服欧洲婴幼儿的治疗孤儿地位。
本研究的目的是比较2007年塞尔维亚、德国和美国有适合12岁以下儿童使用标签的适合儿童年龄的口服制剂的可获得性，并调查对儿童具有治疗重要性的某些药物类别是否有较少适合儿科患者的标注适当的药物。确定适合儿童年龄的口服剂型及其许可和标签状态信息的主要来源是2007年的官方药物信息手册和国家处方集。
口服药物的总体可获得性在美国最高（304种），其次是德国（235种）和塞尔维亚（156种）。在所有这些口服药物中，标注适合儿童年龄的儿科剂型的可获得性仅在21.2%至47.7%之间。此外，三国之间在某些药物类别（如心血管药物（塞尔维亚没有）和抗寄生虫药物（塞尔维亚和德国没有））标注适合儿童年龄的剂型的可获得性方面存在显著差异。
我们的数据表明，在有儿科标签的口服药物制剂的数量和类型方面，国家与国家之间仍然存在显著差异。潜在的促成因素包括药物监管过程中的国家特定差异、制药开发能力以及与实施专门针对儿科产品开发和标签的药物监管相关的监管滞后时间。我们假设新的欧洲药品和儿童法规将改善当前不可接受的状况。
