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Pharmakologie der neuen oralen Antikoagulanzien

Pharmacology of the new oral anticoagulants

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Zusammenfassung

Die neuen oralen Antikoagulanzien wie Dabigatran, Rivaroxaban, Apixaban oder Edoxaban zeigen pharmakokinetische und pharmakodynamische Kenndaten vergleichbar denjenigen niedermolekularer Heparine. Maximale Wirkspiegel werden 2 bis 4 Stunden nach Einnahme erreicht, die Halbwertszeiten liegen bei 7 bis 14 Stunden. Die Substanzen unterscheiden sich insbesondere hinsichtlich der renalen Elimination. Dosisanpassung erfolgt lediglich bei Nierenfunktionsstörungen, erhöhtem Blutungsrisiko sowie bei bestimmten Begleitmedikationen. Durch die kurze Wirkdauer der Substanzen ist eine präoperative Therapieumstellung nicht erforderlich. Spezifische Antidots stehen bisher nicht zur Verfügung, eine Antagonisierung der gerinnungshemmenden Wirkung wird allerdings aufgrund der kurzen Wirkdauer nur selten erforderlich sein. Für die Konzentrationsbestimmung im Blut stehen inzwischen spezielle Testverfahren zur Verfügung. Im Notfall schließt eine normale Thrombinzeit bzw. ein normalwertiger Anti-Faktor-Xa-Test das Vorhandensein wirksamer Konzentrationen von Dabigatran bzw. Faktor-Xa-Inhibtoren im Blut aus.

Die neuen oralen Antikoagulanzien werden sowohl in der Thromboseprophylaxe als auch in der (längerfristigen) gerinnungshemmenden Therapie, beispielsweise bei Vorhofflimmern oder nach tiefer Beinvenenthrombose, eingesetzt. Bei Dabigatran liegen Prophylaxedosis (1-mal 220 mg) und therapeutische Dosis (2-mal 110 bis 2-mal 150 mg) recht eng beisammen, bei den Faktor-Xa-Inhibitoren Rivaroxaban und Apixaban entspricht die therapeutische Dosis in etwa dem Doppelten der Prophylaxedosis (Rivaroxaban: Thromboseprophylaxe 1-mal 10 mg, Vorhofflimmern 1-mal 20 mg, Therapie der venösen Thrombose initial 2-mal 15 mg, dann 1-mal 20 mg; Apixaban: Prophylaxedosis 2-mal 2,5 mg, Antikoaglation bei Vorhofflimmern 2-mal 5 mg).

Abstract

New oral anticoagulants, such as dabigatran, rivaroxaban, apixaban, and edoxaban display pharmacologic and pharmacodynamic data similar to low molecular weight heparins. Peak levels are found 2–4 h after oral ingestion and elimination half-lives are in the range of 7–14 h. The drugs differ primarily concerning renal elimination. Dose adjustment is only performed in patients with impaired renal function, high risk of bleeding and patients with co-medications which influence the metabolism or anticoagulant effect of the drugs. Due to the short half-life, perioperative bridging is not necessary. Currently, no specific antidotes are available: however, assay systems are available for measuring the plasma concentration of dabigatran and rivaroxaban. In emergency cases a normal thrombin time excludes relevant levels of dabigatran, whereas a normal anti-factor Xa assay result excludes relevant levels of factor Xa inhibitors.

The new anticoagulants are being used for prophylaxis of venous thrombosis in elective hip and knee surgery, as well as for treatment of venous thrombosis and for prevention of stroke and systemic embolism in patients with atrial fibrillation. Additional indications are to follow. Dabigatran is given at a dose of 110 mg initially 1–4 h after surgery followed by 220 mg once daily for prophylaxis of thrombosis and at doses of 110 mg or 150 mg twice daily for therapeutic anticoagulation. The prophylactic and therapeutic doses of rivaroxaban are 10 and 20 mg and, of apixaban 2.5 mg and 5 mg twice daily, respectively.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Referentenhonorare Bayer, Boehringer Ingelheim, GSK, Daiichi Pharma, Roche Diagnostics, IL.

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  1. IMD Gerinnungspraxis Mannheim, Belchenstr. 1-5, 68163, Mannheim, Deutschland

    C.-E. Dempfle

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Dempfle, CE. Pharmakologie der neuen oralen Antikoagulanzien. Herz 37, 362–369 (2012). https://doi.org/10.1007/s00059-012-3616-y

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