Peak and baseline concentrations of fondaparinux during prophylactic therapy

M. Schindewolf; R. Kanagendran; J. Scheuermann; H. Ackermann; R. Kaufmann; W.-H. Boehncke; R. J. Ludwig; Z. Wolf; E. Lindhoff-Last

doi:10.1055/s-0037-1621772

Phlebologie, Table of Contents

Phlebologie 2011; 40(04): 187-194
DOI: 10.1055/s-0037-1621772

Originalarbeiten

Schattauer GmbH

Peak and baseline concentrations of fondaparinux during prophylactic therapy

Results of a prospective investigation under „real life” clinical practice conditionsGipfel- und Talspiegel-Konzentrationen von Fondaparinux während prophylaktischer BehandlungErgebnisse einer prospektiven Untersuchung unter klinischen „real life“-Be dingungen.

M. Schindewolf

¹Department of Internal Medicine, Division of Vascular Medicine and Haemostaseology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

R. Kanagendran

¹Department of Internal Medicine, Division of Vascular Medicine and Haemostaseology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

J. Scheuermann

¹Department of Internal Medicine, Division of Vascular Medicine and Haemostaseology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

H. Ackermann

²Department of Biomathematics, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

R. Kaufmann

³Department of Dermatology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

W.-H. Boehncke

³Department of Dermatology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

R. J. Ludwig

⁴Department of Dermatology, University Hospital Luebeck, Germany

,

Z. Wolf^*

¹Department of Internal Medicine, Division of Vascular Medicine and Haemostaseology, J.W. Goethe University Hospital Frankfurt am Main, Germany

,

E. Lindhoff-Last^*

¹Department of Internal Medicine, Division of Vascular Medicine and Haemostaseology, J.W. Goethe University Hospital Frankfurt am Main, Germany

› Author Affiliations

Abstract

Summary

Fondaparinux is widely approved for prophylaxis and treatment of venous thromboembolic events (VTE). However, its longer half-life time compared to heparins limits its peri-procedural use.

Aim: To investigate 3h peak and 24h baseline concentrations of fondaparinux when administered for prophylaxis (1 x 2.5 mg qd). Secondary outcome measures: incidences of VTE, bleedings, HIT, allergic skin reactions, 30 days mortality.

Patients, methods: Between 02/2010 and 03/2011, 3h peak and 24h baseline levels of fondaparinux were measured with a chromogenic anti-FXa method in 75 consecutive patients. Medical data were obtained from patients' records.

Results: The 5% and 95% percentile of the 3h peak level were 0.20 μg/ml and 0.83 μg/ml (median: 0.53 μg/ml), and of the 24h baseline level 0.08 μg/ml and 0.53 μg/ml (median 0.21 μg/ml), respectively. An inverse correlation was found between fondaparinux levels and GFRs (rho=-0.617 (3h); rho=-0.648 (24h); p=0.01). Shorter (≤5 days) or longer (≥8 days) duration of prior fondaparinux exposure showed no significantly different 3h peak/24h baseline levels (p>0.6). One progressive thrombosis occurred but no major bleedings, HIT, allergic skin reactions or fatalities.

Conclusions: After fondaparinux exposure, >75% of the patients still had relevant prophylactic 24h baseline levels. This did not coincide with a high rate of bleeding events. Due to the low patient number in this study undergoing surgery or interventions, it remains to be investigated whether or at which concentrations the bleeding risk is increased when baseline levels are within prophylactic ranges.

Zusammenfassung

Hintergrund: Das synthetische Pentasaccharid Fondaparinux, ein indirekter Faktor Xa-Inhibitor, besitzt eine breite Zulassung in der Prophylaxe und Therapie von thromboembolischen Komplikationen. Es hat ein deutlich niedrigeres Risiko für HIT und allergische Reaktionen im Vergleich zu Heparinen. Allerdings bestehen aufgrund seiner längeren Halbwertszeit Einschränkungen im peri-operativen und -inter-ventionellen Bereich, während es für Heparine klare Bridging-Empfehlungen gibt.

Ziel der Untersuchung war es, die 3h-Gipfelund 24h-Talspiegel unter prophylaktischer Fondaparinuxgabe (1 x 2,5 mg/die) und die Häufigkeiten hierunter auftretender Komplikationen (venöse thromboembolische Komplikationen, Blutungen, HIT, allergische Hautreaktionen, 30-Tages-Mortalität) zu ermitteln.

Patienten, Methoden: Zwischen Februar 2010 und März 2011 wurden bei 75 konsekutiven internistischen und chirurgischen Patienten Fondaparinux 3h-Gipfel- und 24h-Talspiegel mittels einer chromogenen anti-FXa-Methode gemessen. Die Erhebung der medizinischen Daten sowie der Komplikationen erfolgte aus den Krankenakten.

Ergebnisse: Die 5% und 95% Perzentilen der 3h Gipfelspiegel lagen bei 0,20 μg/ml bzw. 0,83 μg/ml (Median: 0,53 μg/ml), und der 24h Talspiegel bei 0,08 μg/ml bzw. 0,53 μg/ml (Median: 0,21 μg/ml). Sie waren signifikant, invers negativ mit der glomerulären Filtrationsrate (GFR) korreliert (Spearman Korrelationskoeffizient: rho=-0.617 (3h); rho=-0.648 (24h), p= 0.01) Es ergaben sich keine signifikanten Unterschiede hinsichtlich der gemessenen Fondaparinuxkonzentrationen bei kürzerer (≤ 5 Tage) oder längerer (≥ 8 Tage) vorangehender Fondaparinuxgabe. Die Rate an Komplikationen war niedrig: es traten eine progrediente venöse Thrombose, jedoch keine „Major“-Blutungskomplikationen, HIT, allergische Hautreaktionen oder Todesfälle auf.

Schlussfolgerung: Überraschenderweise wie-sen >75% der Patienten nach 24 Stunden Talspiegel auf, die noch im prophylaktischen Zielbereich lagen. Eine vermehrte Inzidenz von Blutungskomplikationen war nicht zu verzeichnen. Um eine Aussage treffen zu können, ob und ab welchen gemessenen Anti-Xa-Spiegeln mit einem gehäuften Auftreten von Blutungen zu rechnen ist, und wann eine prophylaktische Therapie mit Fondaparinux präoperativ/-interventionell abgesetzt warden sollte, sind größere Fallzahlen solcher Patienten notwendig, die sich einer Operation oder einer Intervention unterziehen.

Keywords

Fondaparinux - pharmacokinetics - peak level - baseline level

Schlüsselwörter

Fondaparinux - Pharmakokinetik - Gipfelspiegel - Talspiegel

Full Text

References

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