In 2012 the U.S. Food and Drug Administration (FDA) issued a recommendation that sildenafil should not be prescribed to children (ages 1 through 17) for pulmonary arterial hypertension (PAH). This recommendation followed the conclusion of two pediatric clinical trials that lasted from 2003-2011 studying 234 children ages 1 to 17. According to the American Heart Association, the trials found children taking higher doses had a higher risk of death than those taking lower doses, and lower doses were not effective.
Since that time, the same drugs have also been linked to the dangerous side effect of increasing risk of developing melanoma, the most deadly form of skin cancer. Harvard researchers published findings in 2014 that, compared to those who had never used the drug, men who had ever used sildenafil in their lifetime had double the risk of developing melanoma. In subsequent years, several other studies since have had similar implications.
In 2014, the year that the first big study was published linking sildenafil and other drugs known as PDE5 inhibitors, used to treat erectile dysfunction, to melanoma, the FDA actually came back and relaxed its initial 2012 warning about sildenafil use in children, saying that if doctors felt the benefits outweighed the risks, they could prescribe the drugs to children.
This change of tone might have been in response to a meeting the agency had in 2014 with the American College of Cardiology, the American Heart Association and the American Academy of Pediatrics, a first collaborative meeting of its kind. The group together known as the Joint Council on Congenital Heart Disease (JCCHD) wanted to discuss sildenafil, marketed as Revatio, for children, which at the time had been one of a limited number of available treatments for children with pulmonary hypertension.
“The FDA felt it had no choice but to issue a warning” due to the increased deaths, said Craig Sable, M.D., lead author of a recent health policy statement just released jointly by the FDA and the JCCHD, according to the American Heart Association.
The statement addressing pediatric heart research issues acknowledges numerous obstacles in testing medications for children and the fact that in the United States less than half of the approved drugs actually have data supporting their use in children. This leads to much off-label prescribing, with the statement asserting that this is so common that most hospitalized children are prescribed at least one off-label medication.
According to the American Heart Association, the groups call for change in how drugs are developed and tested in children and said that “drug trials must be flexible enough to overcome enrollment problems and other barriers to research in children with heart disease, while giving pediatricians proof that the treatments they’re using actually work.”
American Heart Association