Zusammenfassung
Therapeutische Äquivalenz zwei wirkstoffgleicher Medikamente wird angenommen, sobald
Bioäquivalenz, d. h. vor allem eine vergleichbare Bioverfügbarkeit, belegt ist. Unter
dieser Regelung sind relevante Diskrepanzen selten geworden, jedoch nicht gänzlich
verschwunden. Dies weist auf immer noch bestehende Schwachpunkte des geltenden Zulassungsverfahrens
hin, die im Einzelnen diskutiert werden. Der Therapeut muss Situationen unterscheiden,
in denen eine unzureichende Behandlung ohne schwerwiegende Folgen bleibt - etwa beim
Gebrauch analgetischer Wirkstoffe -, und solchen, bei denen die Bioverfügbarkeit kritische
Bedeutung besitzt. Hierzu zählt insbesondere die Anwendung von Wirkstoffen geringer
therapeutischer Breite und solcher Wirkstoffe, deren Wirksamkeit essenziell, aber
nur schwer nachprüfbar ist, in der Rheumatologie etwa bei prophylaktischer oder krankheitsmodifizierender
Medikation. Ciclosporin kann in beiden Kategorien als Beispiel dienen. Im Bereich
der rheumatologischen Pharmakotherapie finden sich Hinweise darauf, dass wirkstoffgleiche
Präparate im Fall der NSAR/ASS sowie bei Ciclosporin und Omeprazol nicht in jedem
Fall austauschbar sind. Keine negativen, teils auch positive Berichte liegen für D-Penicillamin,
Glukokortikoide, Goldsalze, Hydroxychloroquin, Methotrexat, Minocyclin und Sulfasalazin
vor. Bei der Entscheidung zwischen wirkstoffgleichen Präparaten sollte der Therapeut
die Art der Indikation und des betreffenden Pharmakons berücksichtigen. Er sollte
offen für die Möglichkeit präparatbedingter Therapieprobleme bleiben und entsprechende
Mitteilungen von Patienten ernst nehmen. Letztlich muss auch hier die eigene Erfahrung
aktiv entwickelt werden. Ist die Entscheidung einmal getroffen, sollte das Präparat
- Original oder Nachahmer - nicht mehr unnötigerweise gewechselt werden. Dies allerdings
ist im Rahmen der Aut-idem-Regelung eine nur schwer zu verwirklichende Forderung.
Abstract
Therapeutic equivalence of two drugs with the same active ingredient is assumed if
bioequivalence (first of all, a comparable bioavailability) has been demonstrated.
With this ruling in place, relevant discrepancies have become rare although not a
matter of the past. This points to persisting flaws in the current set of rules regulating
approval of generic drugs (details will be discussed). In practical therapy, it is
important to discriminate between situations in which insufficient treatment will
remain without serious consequences (for example in the use of analgesics) and settings
in which bioavailability is of crucial importance. The latter is especially true of
drugs with narrow therapeutic index and agents whose actions are vital but difficult
to control such as preventive/disease modifying drugs in rheumatological pharmacotherapy.
In both categories, cyclosporine can serve as an example. Focusing on rheumatology,
there is evidence that preparations containing NSAIDs, aspirin, cyclosporine or omeprazole
are not freely interchangeable in each case. No negative, in some cases positive reports
are available on d-penicillamine, corticosteroids, gold salts used in chrysotherapy
(aurotherapy), hydroxychloroquine, methotrexate, minocycline, and sulfasalazine. When
choosing from various drugs with the same active ingredient, the physician should
consider the indication and the properties of that agent. He should remain open-minded
for possible preparation-related problems and take pertinent patient reports serious.
Last but not least, the physician must actively develop his experience with individual
preparations. Once a decision on a preparation has been made, no unnecessary changes
should be allowed. Unfortunately, the last recommendation is hard to follow in countries
such as Germany which have adopted the “aut idem” rule (latin for: “or the same”)
which makes it mandatory for the pharmacist to dispense a lower-priced “aut idem”
preparation unless ruled out by the physician.
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Prof. Dr. med. Karl-Uwe Petersen
Pharmakologe und Toxikologe
Oberdorfstraße 22
52072 Aachen
eMail: KarlUwe.Petersen@post.rwth-aachen.de
