BETHESDA, MD 31 August 2012—The results of a long-term study of sildenafil in children with pulmonary hypertension, a potentially fatal disorder, prompted FDA on August 30 to recommend against using the phosphodiesterase-5 inhibitor in these patients.
According to FDA, the study showed that the dosage regimen with the lowest risk of death did not improve the children's ability to exercise.
According to the researchers, the study showed that medium- and high-dose sildenafil may be efficacious in treating pulmonary hypertension and that, with further investigation, the optimal age- and weight-based dosage can be determined.
Both FDA and the researchers reported that none of the participants in the study died during the initial 16 weeks.
FDA reported that the first deaths occurred after about one year and at fairly constant rates in the three dosage groups. The agency calculated that the patients who received high-dose sildenafil died at a significantly higher rate than did patients in the low-dose group.
The researchers reported that the higher risk of death in the high-dose group "appeared to occur" after two years of treatment. None of the deaths were considered by the investigators to have been caused by sildenafil. They reported that 20% of the patients in the high-dose group have died.
Pulmonary hypertension itself can be fatal. The researchers, citing three journal articles, reported that before therapies specific to the treatment of pulmonary hypertension became available less than 67% of children with the disease survived one year after diagnosis.
FDA said the results of the study and a warning about the use of sildenafil in children will be added to the labeling for Revatio.
Revatio, by Pfizer Inc., is the version of sildenafil that is intended for use in the treatment of pulmonary arterial hypertension, also known as World Health Organization group I pulmonary hypertension.
FDA originally approved Revatio in 2005 to improve the ability of adults with pulmonary hypertension to exercise.
In approving Pfizer's new drug application, the agency gave the company a deferment for submitting an assessment of the product's safety and effectiveness in pediatric patients.
The agency (PDF) had already asked the company to conduct studies of sildenafil in pediatric patients with pulmonary hypertension.