Zusammenfassung
Hintergrund
Um die Vergleichbarkeit aller Latanoprost-Präparate bzw. deren Generika zu prüfen, wurde die Wirkstoffkonzentration der in Deutschland verfügbaren Präparate getestet. In Europa wird für einen Bereich von (− 20 bis + 25 %) von einer Bioäquivalenz ausgegangen.
Material und Methoden
Verfügbare Präparate wurden beschafft und erfasst. Die Konzentration von Latanoprost und Benzalkoniumchlorid wurde bei 23 Produkten mittels „high-performance liquid chromatography“ (HPLC) in einem validierten Referenzlabor bestimmt. Außerdem wurden noch das mittlere Tropfenvolumen und der pH der Wirkstoffformulierung getestet. Die Verpackungen wurden erfasst und die Lesbarkeit der Gebrauchsinformationen überprüft.
Ergebnisse
Alle Produkte enthielten weniger als 50 μg/ml Latanoprost. Die unterschiedlich erniedrigte Wirkstoffmenge (mittlere Abweichung: − 7,39 %, ± 2,8 %) wurde noch von Schwankungen der Tropfenmenge (mittleres Gewicht 0,03 g, ± 0,002 g) überlagert. Dafür war die Benzalkoniumchlorid-Konzentration zum Teil deutlich höher (Median Abweichung 5,45 %, min: − 2,5 %, max: 11,5 %). Der pH-Wert des ursprünglichen Originalpräparates und seiner Generika hatte einen Median von 6,78 (min: 6,62, max: 6,81) und unterschied sich somit von einer unkonservierten Latanoprost-Formulierung (pH 7,18). Die beiliegende Gebrauchsinformation der meisten Generika war aufgrund einer zu kleinen Schriftgröße für Menschen mit reduzierter Sehschärfe nicht lesbar.
Schlussfolgerungen
Für die Verordnung von Ophthalmologika ist zu berücksichtigen, dass verschiedene Einflussfaktoren zu einer schwankenden Drucksenkung im Ergebnis beitragen können. Angesichts einer fehlenden Versorgungsforschung ist unklar, inwieweit sich auch deutliche Unterschiede einer Tropfflasche mit anderem Erscheinungsbild und erhöhtem Druckpunkt auf die nicht unproblematische Adhärenz von Glaukompatienten auswirken können.
Abstract
Background
To test the interchangeability of the commercially available (in Germany) latanoprost drugs and their generics respectively, the concentration of the active substance was tested. Guidelines of the European Medicines Agency postulate a sufficient bioequivalence, if the range of the agent is within 80–125 % of the original drug.
Methods
All compounds of latanoprost were procured registered. The concentration of latanoprost and benzalkoniumchloride was measured by high-performance liquid chromatography (HPLC) in a validated reference labroratory for 23 generics. In addition, the mean volume of drops and the pH of the formulation were measured. The packaging label and the readability of the enclosed information leaflet were checked.
Results
All products contained less than 50 μg/ml latanoprost. The deviating reduction of the active substance (mean: − 7.39 %, ± 2.8 %) was accompanied by fluctions of the eyedrops’ mass (mean: 0.03 g, ± 0.002 g). The concentration of benzalkonium chloride was mostly increased (median: 5.45 %, min: − 2.5 %, max: 11.5 %). The pH of the original drug and the generics (median 6.78, min: 6.62, max: 6.81) was similar to the original drug, but was significantly different from an unpreserved formulation (pH 7.18). Due to type size, the packaging leaflet was illegible for humans with impaired vision.
Conclusions
Before prescribing generics in ophthalmology, different factors have to be considered, which might influence the amount of IOP lowering in effect. In the absence of healthcare research it is still unclear, how different bottle forms of eyedrops—such as appearance (e.g. Cyrillic characters) or pressure point (administration)—reduce the adherence of glaucoma patients.
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Interessenkonflikt. M.A. Leitritz, H.-P. Lipp, B. Voykov und F. Ziemssen geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Leitritz, M., Lipp, HP., Voykov, B. et al. Originalpräparat versus Generika – Latanoprost. Ophthalmologe 112, 127–139 (2015). https://doi.org/10.1007/s00347-014-3097-x
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DOI: https://doi.org/10.1007/s00347-014-3097-x