Risk-benefit considerations when prescribing phosphodiesterase-5 inhibitors in children

Expert Opinion on Drug Safety
Alan G MageeSiân Bentley

Abstract

Sildenafil (Revatio®) and tadalafil (Adcirca®) are specific inhibitors of the phosphodiesterase-5 enzyme and produce pulmonary vasodilation by inhibiting the breakdown of cyclic guanosine monophosphate (cGMP) in the walls of pulmonary arterioles. We focus on the efficacy and safety of sildenafil and tadalafil in the treatment of pulmonary hypertension (PH) in children through a PubMed literature search. Although used since 1999 in the treatment of PH in children, it is only in the past few years that robust evidence for the use of sildenafil has emerged principally in the pivotal STARTS-1 study. The open-label extension of this study, STARTS-2, has revealed safety concerns substantiated by FDA post marketing surveillance leading to recommendations to use lower doses. More recently, tadalafil has been introduced allowing once daily dosing with apparently similar efficacy to sildenafil in children. Recently there have been suggestions that sildenafil and tadalafil may have a place in treating muscular dystrophy.

References

Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P KubesD N Granger
Jul 28, 1999·Anesthesiology·A M Atz, D L Wessel
Nov 27, 2002·The European Respiratory Journal·D ChemlaS Brimioulle
Feb 18, 2003·Cardiology·Josef Finsterer, Claudia Stöllberger
Sep 6, 2003·American Journal of Respiratory and Critical Care Medicine·Ralph T SchermulyFriedrich Grimminger
Nov 5, 2003·American Journal of Respiratory and Critical Care Medicine·Toby J TowardKenneth J Broadley
Jun 15, 2004·Journal of the American College of Cardiology·Marc HumbertMarlene Rabinovitch
Mar 2, 2005·Basic Research in Cardiology·Benedetta TantiniNazzareno Galié
Apr 13, 2005·International Journal of Cardiology·Ageliki A KaratzaAlan G Magee
Aug 3, 2006·Nature Reviews. Drug Discovery·Hossein A GhofraniFriedrich Grimminger
Aug 19, 2006·American Journal of Respiratory and Critical Care Medicine·Poongundran NamachivayamLara S Shekerdemian
Aug 22, 2006·European Journal of Clinical Investigation·K LunzeI Schulze-Neick
Sep 22, 2006·International Journal of Impotence Research·N MehrotraB Meibohm
Nov 28, 2007·European Journal of Clinical Pharmacology·Gary BurgessJasper Dingemanse
Mar 28, 2009·The European Respiratory Journal·G KovacsH Olschewski
Sep 15, 2009·The European Respiratory Journal·N GalièG Simonneau
Dec 2, 2009·Archives of Disease in Childhood. Fetal and Neonatal Edition·Maurice J AhsmanRon A Mathot
Apr 3, 2010·Journal of the American College of Cardiology·Christian ApitzAndrew N Redington
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Candace M AdamoJoseph A Beavo
Dec 9, 2010·Cardiology in the Young·Tilman HumplIan Adatia
Jan 12, 2011·British Journal of Clinical Pharmacology·Jean-Luc VachieryRobert Naeije
Jan 14, 2012·Lancet·Rolf M F BergerRobyn J Barst
Mar 10, 2012·Pediatric Cardiology·Shinichi TakatsukiDavid Dunbar Ivy
Dec 12, 2012·American Journal of Respiratory and Critical Care Medicine·Steven H AbmanUNKNOWN Pediatric Pulmonary Hypertension Network (PPHNet)
Jan 1, 2016·Drug, Healthcare and Patient Safety·Andrew L Dodgen, Kevin D Hill

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