Varnostni vidiki umika zdravil s tržišča med leti 1960 in 2018

Arh, Ana (author), Peterlin Mašič, Lucija (mentor)

V skladu z zakonodajo o zdravilih morajo vsa nova zdravila pred odobritvijo s strani regulativnih organov ustrezati vsem zahtevam za kakovost, učinkovitost in varnost. Vendar se v določenih primerih šele po uporabi zdravila v klinični praksi pokaže, da je potreben umik zdravila s tržišča, tudi iz vidika varnosti. Namen magistrske naloge je pregled umaknjenih zdravil s tržišča v obdobju med leti 1960 in 2018, ki so bila umaknjena iz varnostnih vidikov in predstavitev različnih tipov toksičnosti, zaradi katerih so bila zdravila umaknjena. Za pregled umaknjenih zdravil smo uporabili več podatkovnih baz. Primarna med njimi je bila baza »Withdrawn«. Za iskanje umaknjenih zdravil smo uporabili tudi strokovne članke, ki smo jih našli v podatkovnih zbirkah PubMed in Google Scholar. Osredotočili smo se na zdravila z majhno molekulsko maso (»klasična zdravila« z molekulsko maso do 1 kDa), ki so bila umaknjena iz varnostnih vidikov. Za vsa zbrana zdravila smo poiskali leto umaknitve, ATC skupino, terapevtsko skupino, zdravstveno stanje, ki je vodilo do umika, in države v katerih je bilo zdravilo umaknjeno. Glede na vse zastavljene kriterije smo za obdobje med leti 1960 in 2018 našli 172 zdravil, ki so bila s tržišča umaknjena iz varnostnih vidikov. Največ zdravil je bilo umaknjenih v obdobju med leti 1980 in 1989, in sicer 30,8 % (53/172). Glede na umik zdravil po državah je bilo s celotnega svetovnega tržišča umaknjenih 13,4 % (23/172) zdravil, s celotne Evropske unije pa 12,2 % (21/172) zdravil. Znotraj EU je bilo največ (41) zdravil umaknjenih iz Francije. Najpogostejši vzrok za umik zdravil iz varnostnih razlogov je bil pojav hepatotoksičnosti. Ta je botrovala k umiku 22,7 % (39/172) zdravil. Sledita multipla toksičnost, ki predstavlja skupek več različnih tipov toksičnosti na organske sisteme, zaradi katere je bilo umaknjenih 19,2 % (33/172) zdravil in kardiovaskularna toksičnost, ki je povzročila umik 11,3 % (20/172) zdravil. Umik zdravil s tržišča je zahteven postopek in predstavlja velik finančni izpad za imetnika dovoljenja za promet z zdravilom, hkrati pa predstavlja težave za vse tiste paciente, ki so zdravilo uporabljali. Zato je nujno potrebno, da se spremljanje zdravil na tržišču posodablja in izboljšuje v koraku s časom.

• Language: Slovenian
• Keywords: farmakovigilanca, toksičnost zdravil, umik zdravil s tržišča, podatkovna baza »Withdrawn«
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-141550
• Publication date in RUL: 01.10.2022

Secondary language

• Language: English
• Title: Safety aspects of medicines withdrawal from the market between 1960 and 2018

Abstract

According to the pharmaceutical legislation, all new medicinal products must meet all quality, efficacy, and safety requirements before they can be approved by the regulatory authorities. However, in certain cases, it becomes apparent only after a medicine has been used in clinical practice, that it is necessary to withdraw a medicine from the market, also from a safety perspective. This study aims to provide an overview of the withdrawn medicinal products from the market between 1960 and 2018 for safety reasons and to describe the different types of toxicity due to which the drugs were withdrawn. We used several databases to review the withdrawn drugs. The primary one was the »Withdrawn« database. We also used scientific articles in PubMed and Google Scholar to search for withdrawn drugs. Our focus was on low molecular weight drugs ("classical drugs" with a molecular weight of up to 1 kDa) which were withdrawn due to safety reasons. For all collected drugs, we searched for the year of withdrawal, the ATC group, the therapeutic group, the adverse effects that led to the withdrawal, and the countries in which the drug was withdrawn. Based on all established criteria, we found 172 withdrawn drugs from the market for safety reasons between 1960 and 2018. Most of the drugs, 30.8 % (53/172) were withdrawn from the market between 1980 and 1989. In terms of countries, 13.4 % (23/172) of medicines were withdrawn globally and 12.2 % (21/172) were withdrawn across the European Union. Within the EU, France had the highest number of withdrawals (41). The most common cause of withdrawals for safety reasons was the occurrence of hepatotoxicity. It was responsible for 22.7 % (39/172) of the withdrawals, followed by multiple toxicity which caused the withdrawal of 19.2 % (33/172) of the drugs, and cardiovascular toxicity which caused the withdrawal of 11,3 % (20/172) of the drugs. The withdrawal of medicinal products is a complex procedure and means not only a significant financial loss for the marketing authorization holder but also problems for all those patients who have used the medicinal product. Therefore, it is important that the monitoring of medicines on the market is updated and improved to stay up to date.

• Keywords: pharmacovigilance, drug toxicity, withdrawal of drugs from the market, »Withdrawn« database