| Abstract | Oko je složen i osjetljiv organ u kojem minimalna oštećenja mogu rezultirati znatnim promjenama u funkciji vida. Oftalmičke nuspojave mogu se javiti kada se određeni lijek primjenjuje lokalno ili sistemski. Oftalmičke nuspojave obično nisu kontinuirano prepoznavane, iako mogu biti učestale ili specifično povezane s lijekom ili skupinom lijekova. Takve nuspojave često se ne prepoznaju tijekom kliničkih ispitivanja i opažaju se tek nakon primjene lijeka u većoj skupini pacijenata. O tome koliko prikupljanje i analiza prijava sumnji na nuspojave pridonosi znanju o lijekovima i povećanju sigurnosti primjene lijekova, pokazuje stalno i kontinuirano revidiranje i dopunjavanje Sažetaka opisa svojstava lijekova i Uputa o lijekovima koji su važan i aktualan izvor informacija o rizicima primjene određenog lijeka za zdravstvene djelatnike i bolesnike.
Cilj i hipoteze istraživanja: Cilj ovog specijalističkog rada je sustavno analizirati oftalmičke nuspojave lijekova i klasificirati nuspojave unutar definiranih granica učestalosti, a vezano za farmaceutski oblik i način primjene lijeka.
Hipoteza 1: Korištenjem takvog pristupa analize nuspojava moguće je identificirati lijekove koji uzrokuju učestale i ozbiljne oftalmičke nuspojave.
Hipoteza 2: Većina lijekova u čijem je Sažetku opisa svojstava lijeka navedena oftalmička nuspojava izdaje se uz liječnički recept, dok je manji broj takvih lijekova u bezreceptnom statusu.
Materijali i metode: Napravljen je pregled objavljene znanstvene literature uz pomoć baza podataka PubMed i Cochrane s ciljem identifikacije, preglednog prikaza i analize lijekova koji uzrokuju specifične oftalmičke nuspojave te identifikacije područja posebnih oftalmičkih nuspojava. Dodatno su oftalmičke nuspojave lijekova analizirane korištenjem pregleda
Sažetaka opisa svojstava lijekova objavljenih u bazi lijekova Agencije za lijekove i medicinske proizvode (HALMED).
Rezultati: Pretraga Sažetaka opisa svojstava lijeka dostupnih u bazi lijekova HALMED-a pokazala je da 371 djelatna tvar (ili kombinacija djelatnih tvari) u lijekovima koji se izdaju na recept stavljenim u promet u Republici Hrvatskoj izaziva jednu ili više oftalmičkih nuspojava. Od 29 djelatnih tvari u lijekovima koji se izdaju na recept, a koji vrlo često izazivaju oftalmičke nuspojave, sljedećih 6 sistemskih lijekova izaziva ozbiljne oftalmičke nuspojave: acitretin (upala mukoznih membrana (kseroftalmija)), amiodaron (mikrodepoziti u rožnici), kobimetinib (serozna retinopatija), lakozamid (diplopija), tretinoin (upale očne spojnice), i zonisamid (diplopija). Lijekovi koji se primjenjuju u prednji segment oka ne izazivaju ozbiljne oftalmičke nuspojave s vrlo čestom učestalošću prema dostupnim literaturnim podacima i temeljem rezultata pretrage HALMED baze lijekova. Pronađeno je da je ranibizumab jedini lijek na tržištu u Republici Hrvatskoj koji se invazivno primjenjuje u stražnji segment oka i koji izaziva ozbiljne oftalmičke nuspojave s vrlo čestom učestalošću (vitritis, ablacija staklovine, krvarenje mrežnice). Većina lijekova u čijem je Sažetku opisa svojstava lijeka navedena oftalmička nuspojava izdaje se na liječnički recept (371 djelatna tvar (ili kombinacija djelatnih tvari)), dok je manji broj takvih lijekova u bezreceptnom statusu (23 djelatne tvari (ili kombinacije djelatnih tvari)).
Zaključak: Oftalmološke komplikacije lijekova najčešće su rijetke, prolazne i blagog do umjerenog intenziteta. Spontano prijavljivanje nuspojava važan je dio praćenja sigurnosti primjene lijekova; dok su neprijavljivanje nuspojave kao i nepotpuni podaci o bolesniku, terapiji i okolnostima razvoja određene oftalmičke nuspojave njegova glavna ograničenja. Neke oftalmičke nuspojave sistemskih lijekova mogu biti česte i zahtijevaju oftalmološki pregled. Neophodne su edukacije liječnika i ljekarnika, te razvoj multidisciplinarnih protokola za suradnju s drugim specijalistima u svakom slučaju propisivanja visoko rizičnih lijekova. |
| Abstract (english) | The eye is a complex and sensitive organ in which minimal impairment can produce a substantial change in eye function. Ophthalmic adverse drug reactions might occur when a particular drug is administered locally or systemically. Ophthalmic adverse drug reactions are usually not continuously detected, although they might be either frequent or specific of a drug or drug group. These adverse events are frequently not recognized during the clinical trial phases and may not appear until the drug is marketed and used by larger numbers of patients. The collection and analysis of reports of suspected adverse reactions contributes to knowledge about drugs and increases the safety of medicinal products. These efforts are further reflected in constant and continuous review and updates of the Summary of Product Characteristics (SmPC) and Package leaflet (PL) that represent important and timely source of information about the risks of cetrain drug administration for healthcare professionals and patients.
Objectives and hypotheses: The aim of this reviw was to systematically analyze the ophthalmic adverse drug reactions and classify them within the defined boundaries of the frequency with respect to the pharmaceutical form and method of drug administration.
Hypothesis 1: Using this approach of adverse reaction analysis, it is possible to identify drugs that cause common and serious ophthalmic adverse reactions.
Hypothesis 2: Most of the drugs which have listed ophthalmic adverse reaction(s) in the SmPC have prescription-only status, while a smaller number of such drugs have „over-the-counter“ status.
Materials and methods: A review of published scientific literature was performed using the PubMed and Cochrane databases, in order to identify, review and analyse drugs causing specific ophthalmic adverse reactions as well as to identify fields of specific ophthalmic adverse drug reactions. In addition, the ophthalmic adverse drug reactions were analyzed searching the SmPCs published in the medicinal products database of Agency for Medicinal Products and Medical Devices of Croatia (HALMED).
Results: Analysis of SmPCs available in the medicinal products database of HALMED showed that 371 active substance (or combination of active substances) in drugs with prescription-only status marketed in the Republic of Croatia, causes one or more ophthalmic adverse reactions. Out of 29 active substances in drugs with prescription-only status, which very often cause ophthalmic adverse reactions, the following 7 systemic drugs cause serious ophthalmic adverse reactions: acitretin (inflammation of the mucous membranes (xerophthalmia)), amiodarone (corneal microdeposits), kobimetinib (serous retinopathy), lacosamide (diplopia), tretinoin (conjunctivitis, keratitis), and zonisamide (diplopia). Most of the drugs for which ophthalmic adverse reaction is listed in the SmPC have a prescription-only status (371 active substance (or combination of active substances)), while a smaller number of such drugs have „over-the-counter“ status (23 active substance (or combination of active substances)). Medicinal products that are administered in anterior segment of the eye do not cause serious ophthalmic adverse reactions with very often frequency. It was found that ranibizumab is the only marketed medicinal product in Republic of Croatia that is administered invasively in the posterior segment of the eye and very often causes serious ophthalmic adverse reactions (vitritis, ablation of vitreous body, retinal hemorrhage).
Conclusion: Ophthalmologic drug complications are usually rare, transient and mild to moderate intensity. The spontaneous reporting of adverse reactions is an important part of monitoring the safety of medicinal products; while failure to report adverse reactions and incomplete data about the patient, the treatment and conditions of developing a particular ophthalmic adverse reactions are its main limitations. Some ophthalmic adverse reactions of systemic drugs can be frequent and require ophthalmologic examination. Education of physicians and pharmacists is essential, as well as the development of multidisciplinary protocols for cooperation with other specialists for each prescription of the high-risk medicinal products. |
