Çocukluk çağı, dinamik ve evre evre fizyolojik değişikliklerin olduğu bir dönemdir. Pediatrik popülasyonda görülen farmakokinetik ve farmakodinamik farklılıklar, ilaç kullanımı esnasında etkililik ve güvenlilik başta olmak üzere çeşitli sorunlara yol açabilmektedir. Buna göre çocuklarda kullanılacak ilaçların, yaş grubuna özgü klinik araştırmalarla incelenip, onaylarının ayrıca alınması gerekmektedir. Oysa çocuklara özgü klinik araştırma ve bu yaş grubunda onaylı endikasyona sahip ilaç sayısı, çeşitli idari ve prosedürel nedenlerle kısıtlıdır. Hekimlerin, çocuk hastaların ilaç ile tedavisini düzenlerken çocukta kullanım endikasyonu onayı olmayan müstahzarları, sıklıkla ekstrapolasyon yoluyla kullandığı bilinmektedir. İlaçların, ruhsat aldıkları alan dışındaki farklı endikasyon, doz, uygulama şekli, yaş grubu, özel popülasyon vb. kullanımları 'endikasyon dışı ilaç kullanımı (EDİK)' olarak adlandırılır. EDİK oranı çocuklarda yüksek seyretmekte, özellikle küçük yaş gruplarında hemen hemen tüm ilaçların endikasyon dışı kullanılmak zorunda kalınabildiği durumlar görülmektedir. Özellikle son 20 yılda tüm dünyada, çocuklarda klinik araştırmaların artırılması için yapılan düzenlemeler ise çocuklarda ilaç kullanımı ile ilgili kanıta dayalı bilgi hacmini, dolayısıyla çocuklarda endikasyon onayı olan ilaç sayısını artırmaya başlamıştır. Bu gelişmelerin, pediatrik popülasyonda EDİK pratiğini mümkün olduğunca sınırlamaya yardımcı olacağı aşikârdır. Ancak EDİK'in rutin olmaktan öte istisnai durumlarda uygulanması hedefine ulaşmak için uzun zaman gerektiği göz önünde bulundurulduğunda, çocuklarda farmakoterapi sürecinin daha başarılı yönetilmesi için ilave yönlendirmelere ihtiyaç duyulmaktadır. Bu çalışmada, çocuklarda EDİK'in nedenleri, dünyada ve Türkiye'deki güncel durumu ve azaltılması/rasyonel yönetilmesi için atılabilecek adımlar ele alınmıştır.
Anahtar Kelimeler: Endikasyon dışı; ilaç kullanımı; pediatri; klinik araştırmalar; rasyonel farmakoterapi
Childhood is a period with dynamic physiological changes stage by stage. Pharmacokinetic and pharmacodynamic variations in pediatric population can cause various problems, especially efficacy and safety issues during drug use. Hence, drugs to be used in children should also be investigated and approved through clinical trials specific to the age group. However, the number of clinical trials and drugs with approved indications in children are limited for a variety of administrative and procedural reasons. Thus physicians tend to extrapolate drug information when treating their pediatric patients with unapproved indication in pediatric population. The use of drugs outside their approved purpose, including different indications, doses, administration forms, age groups, or special populations etc. İs called "off-label drug use" (OLDU). Its prevalence is high in children, especially in very young age groups where almost all drugs may have to be used off-label. In the last 20 years, the regulations to facilitate clinical research in children throughout the world have helped to increase the volume of evidence-based information about drug use, thus the number of drugs approved, in children. Obviously, these advances will decrease OLDU practice in children. Considering the long time required to achieve the goal of applying OLDU only in exceptional cases, additional guidance is needed to make the pharmacotherapy more appropriate in children. In this review, causes of pediatric OLDU practice and the current situation in Turkey and globally are evaluated with further discussion of the steps that can be taken for reduction/rational management of OLDU.
Keywords: Off-label; drug use; pediatrics; clinical trials; rational pharmacotherapy
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