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Safety and Tolerability of Targeted Therapies for Pulmonary Hypertension in Children

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Abstract

The objective of this study is to evaluate the safety and tolerability of the pharmacological treatment of pulmonary hypertension in pediatric patients. It is a retrospective, longitudinal, observational study on pediatric patients undergoing treatment with pulmonary targeted therapies. 63 patients were included (51 % male), with a median age of 3.4 years (IQR, 3.6 months–10 years) and a median weight 13 kg (IQR, 6–30 kg). Congenital heart disease was the etiology of pulmonary hypertension in the majority of cases (n = 33) and 28 patients were in NYHA functional class III–IV. The most commonly used drug was sildenafil (n = 79, 56 %), followed by bosentan (n = 27, 23 %), and a combination of both (n = 14, 41 %). 34 patients had adverse reactions (54 %) with an incidence rate of 1.02 per patient per year. The most commonly reported reactions were gastrointestinal symptoms (22 %) and spontaneous erections (22 %) in males. Nine severe adverse reactions (10 %) occurred, requiring eight treatment withdrawal and one hospital admission. Treatment with targeted therapies for pulmonary hypertension is safe in the pediatric population. Severe ADRs were uncommon both in monotherapy and in combination therapy. Combination therapy was associated with a higher rate of ADRs. We observed similar survival rates in children receiving sildenafil doses according to the European Medicines Agency (EMA) recommendations or higher.

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Acknowledgments

The authors thank all of their colleagues who participated in this study for their valuable comments and ideas, particularly Villamañán Bueno, Larrubia Marfil, and Perez Robles. Thanks also to Amber Castle from the Pharmacy Department of Yale–New Haven Hospital and Erica Wagner from the University of Wisconsin–Madison School of Pharmacy for their critical review of the first draft of this article and to the Biostatistics Section of IdiPAZ Institute for the statistical analysis. Translation into English was financed by Pfizer.

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Authors and Affiliations

  1. Department of Pharmacy, Hospital Universitario La Paz, Madrid, Spain

    T. Roldan, J. A. Romero & A. Herrero

  2. Pediatric Pulmonary Hypertension Unit, Department of Pediatric Cardiology, Hospital Universitario La Paz, Madrid, Spain

    L. Deiros, F. Gutierrez-Larraya & M. J. Del Cerro

Authors
  1. T. Roldan
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  2. L. Deiros
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  3. J. A. Romero
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  4. F. Gutierrez-Larraya
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  5. A. Herrero
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  6. M. J. Del Cerro
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Corresponding author

Correspondence to M. J. Del Cerro.

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Roldan, T., Deiros, L., Romero, J.A. et al. Safety and Tolerability of Targeted Therapies for Pulmonary Hypertension in Children. Pediatr Cardiol 35, 490–498 (2014). https://doi.org/10.1007/s00246-013-0811-4

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  • DOI: https://doi.org/10.1007/s00246-013-0811-4

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