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Sildenafil zur Behandlung der pulmonalen arteriellen Hypertonie (PAH)

Erhöhte Mortalität unter Hochdosistherapie

Sildenafil for treatment of pulmonary arterial hypertension (PAH)

Increased mortality with high-dose therapy

  • Arzneimitteltherapie
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Die pulmonale arterielle Hypertonie (PAH) im Kindesalter ist ein seltenes, aber schwerwiegendes Krankheitsbild.

Sildenafil zur Behandlung der PAH – Studienergebnisse

Der Phosphodiesterase-5-Hemmstoff Sildenafil gehört zu den wenigen zugelassenen Therapieoptionen für das Kindesalter. In einer aktuellen randomisierten, plazebokontrollierten Studie wurden seine Wirksamkeit und Sicherheit bei Kindern ab 1 Jahr untersucht, dabei konnte nur eine Effektivität beim mittleren Dosisregime gezeigt werden. In der darauf aufbauenden Langzeitsicherheitsstudie wurde eine dosisabhängige Erhöhung der Mortalitätsrate unter der Hochdosistherapie beobachtet.

Schlussfolgerung

Obwohl in keinem Todesfall ein kausaler Zusammenhang mit Sildenafil gefunden wurde, sind weitere Studien notwendig, um den Stellenwert und das Nutzen-Risiko-Verhältnis der Therapie klar zu definieren. Die häufige Off-Label-Anwendung bei der persistierenden pulmonalen Hypertonie bei Neugeborenen, der bronchopulmonalen Dysplasie oder in Kombination mit dem Endothelinrezeptorantagonisten Bosentan beruht bisher auf schwacher Evidenz und fehlenden Langzeitstudien. Bis weitere Kenntnisse vorliegen, wird geraten, Kinder mit PAH nur innerhalb der zugelassenen Dosisempfehlung mit Sildenafil zu behandeln und den Off-Label-Gebrauch nur unter großer Vorsicht zu realisieren.

Abstract

Background

Pulmonary arterial hypertension (PAH) in children is a rare but serious condition.

Sidenafil for treatment of PAH – Study results

The phosphodiesterase-5 inhibitor sildenafil is one of the few approved treatment options for this age group. A recent randomized, placebo-controlled study evaluated the efficacy and safety of sildenafil in children aged over 1 year and showed efficacy for the moderate dose regimes only. The subsequent long-term safety study found an increased dose-dependent mortality during high-dose treatment.

Conclusions

Although no causality between the deaths and sildenafil was found, further studies are necessary to clearly define the benefit-risk ratio of this therapy. Sildenafil is also commonly used for the off label treatment of persistent pulmonary hypertension in newborns, bronchopulmonary dysplasia or as combination therapy with the endothelin receptor antagonist bosentan; however, this is based on weak evidence and a lack of long-term studies. Until further data are available it is recommended that sildenafil should be used in children only within the licensed dose recommendations and to be particularly careful when used off-label in very young children.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. A. Neubert, S. Botzenhardt, T. Stammschulte, M. Paulides und W. Rascher geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Kinder- und Jugendklinik, Universitätsklinikum Erlangen, Loschgestraße 15, 91054, Erlangen, Deutschland

    A. Neubert, S. Botzenhardt & W. Rascher

  2. Arzneimittelkommission der deutschen Ärzteschaft, Berlin, Deutschland

    T. Stammschulte & M. Paulides

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  1. A. Neubert
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  2. S. Botzenhardt
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  3. T. Stammschulte
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  4. M. Paulides
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  5. W. Rascher
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Correspondence to A. Neubert.

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Neubert, A., Botzenhardt, S., Stammschulte, T. et al. Sildenafil zur Behandlung der pulmonalen arteriellen Hypertonie (PAH) . Monatsschr Kinderheilkd 161, 1029–1036 (2013). https://doi.org/10.1007/s00112-013-2997-1

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