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Unerwünschte Nebenwirkungen von Tapentadol im Vergleich zu Oxycodon

Eine Metaanalyse randomisierter, kontrollierter Vergleichsstudien

Undesired side effects of tapentadol in comparison to oxycodone

A meta-analysis of randomized controlled comparative studies

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An Erratum to this article was published on 28 November 2012

Zusammenfassung

Fragestellung

Mit Tapentadol ist ein neues Analgetikum im klinischen Einsatz, das sowohl als Agonist am μ-Opioidrezeptor wie auch als selektiver Noradrenalinwiederaufnahmehemmer wirkt. Tapentadol soll bei mit klassischen Opioidanalgetika wie Oxycodon vergleichbarer analgetischer Potenz eine deutlich geringere Rate an unerwünschten Nebenwirkungen aufweisen.

Material und Methoden

Es wurde eine systematische Literaturrecherche (MEDLINE, Cochrane-Register, Datenbank des Präparateherstellers) nach randomisierten Studien durchgeführt, in denen Tapentadol zur Schmerztherapie im direkten Vergleich mit Oxycodon eingesetzt worden war. Die Literaturrecherche erfolgte in Übereinstimmung mit den PRISMA-Statements und wurde von Oktober bis Dezember 2010 durchgeführt. Als Hauptzielgröße wurde der jeweilige Anteil an Patienten extrahiert, die während der Schmerztherapie mit Tapentadol oder Oxycodon unter typischen opioidassoziierten Nebenwirkungen, z. B. Übelkeit, Erbrechen, Obstipation oder Juckreiz, litten. Als statistische Kenngröße wurden das relative Risiko (RR) und das 95%-Konfidenzintervall (95%-KI) für das Auftreten dieser Nebenwirkungen unter Tapentadol im Vergleich zu Oxycodon berechnet.

Ergebnisse

Es wurden 9 Studien mit insgesamt 7948 Patienten in diese Übersichtsarbeit eingeschlossen, wobei 2810 mit Oxycodon und 5138 mit Tapentadol in äquianalgetischer Dosierung und mit dokumentiertem, vergleichbarem analgetischem Effekt behandelt wurden. Der Einsatz von Tapentadol geht dabei mit einem signifikant niedrigeren Risiko von Übelkeit (RR: 0,61; 95%-KI: 0,57–0,66), Erbrechen (RR: 0,50; 95%-KI: 0,41–0,60), Obstipation (RR: 0,47; 95%-KI: 0,40–0,56), Schwindel (RR: 0,86; 95%-KI: 0,78–0,95), Schläfrigkeit (RR: 0,76; 95%-KI: 0,67–0,86) und Juckreiz (RR: 0,46, 95%-KI: 0,37–0,58) einher. Diese typischen Nebenwirkungen wurden in allen 9 Studien untersucht. Dagegen war Tapentadol häufiger mit Mundtrockenheit (6 Studien mit 6218 Patienten; RR: 1,79; 95%-KI: 1,40–2,29) und Dyspepsie (1 Studie mit 646 Patienten; RR: 2,75; 95%-KI: 1,09–6,94) assoziiert. Hinsichtlich anderer untersuchter Nebenwirkungen (Diarrhö, Kopfschmerzen, Erschöpfungssymptome) zeigten sich keine signifikanten Unterschiede.

Schlussfolgerungen

Die Ergebnisse zeigen bei vergleichbarer analgetischer Potenz eine Überlegenheit für Tapentadol hinsichtlich der häufigsten opioidtypischen Nebenwirkungen. Aufgrund der noch relativ geringen Anzahl an Primärstudien ist jedoch eine weitere Evaluation in klinischen Untersuchungen wünschenswert.

Abstract

Objective

Tapentadol is a new centrally acting analgesic with a dual mode of action as an agonist of the µ-opioid receptor and as a norepinephrine reuptake inhibitor. The aim of the present study was to evaluate the results from randomized controlled trials investigating the relative amount of adverse effects using tapentadol or oxycodone for the treatment of pain.

Methods

A quantitative systematic review was carried out according to the PRISMA recommendations on randomized controlled trials comparing tapentadol and oxycodone in pain treatment. The incidences of typical adverse side effects of opioid-based analgesic therapy (e.g. nausea, vomiting, obstipation or pruritus) were extracted and the pooled relative risks (RR) with corresponding 95% confidence intervals (CI) were calculated.

Results

A total of 9 trials involving 7,948 patients were included and of these 2,810 patients were treated with oxycodone and 5,138 were treated with tapentadol in equivalent analgesic dosages as documented by an equivalent analgesic effect. The risk of typical opioid-based adverse effects, such as nausea (RR 0.61; 95% CI 0.57–0.66), vomiting (RR 0.50, 95% CI: 0.41–0.60), obstipation (RR 0.47, 95%-CI 0.40–0.56), dizziness (RR 0.86, 95% CI 0.78–0.95), somnolence (RR 0.76, 95% CI 0.67–0.86) and pruritus (RR 0.46, 95% CI 0.37–0.58) was reduced when tapentadol was used for analgesic treatment. These adverse effects were investigated in all nine trials. The risk for dryness of the mouth (6 trials, 6,218 patients, RR 1.79, 95% CI 1.40–2.29) and dyspepsia (1 trial, 646 patients, RR 2.75, 95% CI 1.09–6.94) was increased when tapentadol was used instead of oxycodone. There were no significant differences in the relative risk for any other investigated adverse effect such as dysentery, headache or fatigue.

Conclusion

The results show that using tapentadol significantly reduces the risk of the typical opioid-based adverse effects compared with oxycodone while providing equivalent analgesic treatment.

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  1. Klinik für Anästhesie und Intensivtherapie, Philipps-Universität Marburg, Baldingerstr., 35033, Marburg, Deutschland

    M. Merker, G. Dinges, T. Koch &  A.M. Morin DEAA

  2. Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Würzburg, Würzburg, Deutschland

    P. Kranke

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  1. M. Merker
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Correspondence to A.M. Morin DEAA.

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Merker, M., Dinges, G., Koch, T. et al. Unerwünschte Nebenwirkungen von Tapentadol im Vergleich zu Oxycodon. Schmerz 26, 16–26 (2012). https://doi.org/10.1007/s00482-011-1132-2

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