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


METHODS
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.


CONCLUSIONS
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.
University of Southampton and Royal Brompton and Harefield NHS Foundation Trusts , Southampton and London , UK alan.magee@uhs.nhs.uk.
Alan G
AG
Magee
Sukeshi
S
Makhecha
Siân
S
Bentley
D000818:Animals; D002648:Child; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068581:Tadalafil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D006152:Cyclic GMP
cyclic-GMP; pulmonary arterial hypertension; sildenafil; tadalafil