FDA recommends against use of Revatio in children with pulmonary hypertension

FDA issued a Drug Safety Communication on sildenafil (Revatio, Pfizer), following the observation in a long-term extension of a clinical trial in pediatric patients with pulmonary arterial hypertension (PAH) of an increase in mortality with increasing Revatio dose.

FDA notified healthcare professionals and their medical care organizations that Revatio should not be prescribed to children (aged 1 through 17 years) for PAH.

This recommendation against use is based on a recent long-term clinical pediatric trial showing that: (1) children taking a high dose of Revatio had a higher risk of death than children taking a low dose and (2) the low doses of Revatio are not effective in improving exercise ability.

Treatment of PAH in children with this drug is an off-label use (not approved by FDA) and a new warning, stating the use of Revatio is not recommended in pediatric patients, has been added to the Revatio labeling. The current Revatio label recommends avoiding doses higher than 20 mg, given 3 times a day. The effect of Revatio on the risk of death with long-term use in adults is unknown; FDA is requiring Pfizer to evaluate Revatio’s effect on the risk of death in adults with PAH.

Dr Yvonne Greenstreet, senior vice president and head of the Medicines Development Group for Pfizer Specialty Care, issued the following statement:

“We believe the benefit/risk profile for use of Revatio in adults with pulmonary arterial hypertension remains favorable. The FDA recommends that patients do not change their Revatio dose or stop taking Revatio without talking to their healthcare professional.

In our ongoing commitment to patient safety, we are working with theFDA to determine the best research-based approach to understanding the observation in the pediatric study and its implications, if any, toadults with PAH.

Pulmonary arterial hypertension is a rare, devastating, incurable disease characterized by high blood pressure in the pulmonaryarteries, leading to heart failure and premature death. Revatio has accumulated more than 100,000 patient-years of experience in the treatment of PAH. Pfizer remains committed to improving the lives of patients suffering from this disease.”

Revatio is a phosphodiesterase-5 inhibitor used to treat PAH by relaxing the blood vessels in the lungs to reduce blood pressure and is approved to improve exercise ability and delay clinical worsening of PAH in adult patients (WHO Group I).

Patients and caregivers are advised to not change the Revatio dose or stop taking Revatio without talking to a healthcare professional. Healthcare professionals were reminded that use of this product, particularly chronic use, in children is an off-label indication, not approved by FDA, and is not recommended. See the Drug Safety Communication for the Data Summary from the randomized, double-blind, placebo-controlled clinical trial of 234 patients with PAH, 1 to 17 years of age with mild to moderate symptoms at baseline.