Implications of the U.S. Food and Drug Administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension

Steven H. Abman, John P. Kinsella, Erika B. Rosenzweig, Usha Krishnan, Thomas Kulik, Mary Mullen, David L. Wessel, Robin H Steinhorn, Ian Adatia, Brian Hanna, Jeffrey Feinstein, Jeffrey Fineman, Usha Raj, Tilman Humpl

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Pulmonary arterial hypertension (PAH) contributes to disability and death in children with diverse cardiac, pulmonary, or systemic diseases, and therapeutic options are currently limited. Data from adult studies provide the basis for most PAH-specific therapies; however, many of these medications are commonly used in children on an off-label basis due to the life-threatening nature of PAH. Although currently approved for use in adult PAH, sildenafil is used extensively off-label for the treatment of neonates, infants, and children with PAH. Past studies have generally suggested favorable effects and outcomes in infants and young children with PAH, but these reports are generally uncontrolled observations, except for one single-center trial for persistent pulmonary hypertension of the newborn. Despite extensive clinical experience with sildenafil therapy in children and approval by the European Medicines Agency for its pediatric use in Europe, the U.S. Food and Drug Administration recently issued a warning against the use of sildenafil for pediatric PAH between 1 and 17 years of age due to an apparent increase in mortality during long-term therapy. Although these data are extremely limited, this U.S. Food and Drug Administration review challenges the pediatric PAH community to further assess the efficacy and safety of sildenafil, especially with chronic treatment. Although low doses of sildenafil are likely safe in pediatric PAH, further studies should carefully examine its role in the long-term therapy of children, especially with diverse causes of PAH. Pediatric patients with PAH require close surveillance and frequent monitoring, and persistent sildenafil monotherapy is likely insufficient with disease progression.

Original languageEnglish (US)
Pages (from-to)572-575
Number of pages4
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume187
Issue number6
DOIs
StatePublished - Mar 15 2013
Externally publishedYes

Keywords

  • Pediatric pulmonary hypertension
  • Pulmonary hypertension therapy
  • Sildenafil

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Abman, S. H., Kinsella, J. P., Rosenzweig, E. B., Krishnan, U., Kulik, T., Mullen, M., Wessel, D. L., Steinhorn, R. H., Adatia, I., Hanna, B., Feinstein, J., Fineman, J., Raj, U., & Humpl, T. (2013). Implications of the U.S. Food and Drug Administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine, 187(6), 572-575. https://doi.org/10.1164/rccm.201210-1928PP