Sildenafil (Revatio®) - Updated
March 31, 2014
In August 2012, FDA warned patients and healthcare providers about the risk of using Revatio® for pulmonary arterial hypertension (PAH) in pediatric patients (ages 1 to 17 years old). This recommendation was based on the Sildenafil in Treatment-Naïve Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension (STARTS-1) trial.1 A secondary analysis of this trial found a higher mortality rate in children taking high doses of Revatio® compared to children taking low doses (HR=3.5; p=0.015). The most common causes of death were pulmonary hypertension and heart failure. The STARTS-1 trial also found that low doses are ineffective for improving exercise tolerance in pediatric patients with PAH.
Revatio® is labeled for use in adult patients with PAH to improve symptoms, delay clinical worsening, and increase exercise tolerability. Use of Revatio® in pediatric patients with PAH is an off-label indication and is not recommended. In August 2012, a warning was added to the Revatio® label to include this recommendation and the results of the STARTS-1 trial. The manufacturer, Pfizer, will evaluate if adults who use Revatio® long-term have an increase in mortality.
The new Medwatch Alert issued March 31, 2014 is to clarify FDA recommendations regarding use of sildenafil to treat PAH in children. The FDA recommendation was not intended as an absolute contraindication. Health care professionals must consider the benefits versus risk in each patient when considering the use of sildenafil.
Healthcare providers are reminded that the maximum dose of Revatio® is 20 mg three times daily for adult patients with PAH. Patients taking Revatio® are instructed to continue their current dose and to talk to a healthcare provider if they have any questions about Revatio®. Report any adverse events to FDA’s MedWatch program.
Additional information is available at the following links:
- MedWatch Alert – March 31, 2014
- Drug Safety Communication – March 31, 2012
- MedWatch Alert – August 30, 2012
- Drug Safety Communication – August 30, 2012
- Study Publication (this study did not report statistical comparisons of morality endpoints)
- Barst RJ, Ivy DD, Gaitan G, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naïve children with pulmonary arterial hypertension. Circulation 2012;125:324-334.
March 31, 2014; September 7, 2012; University of Utah, Drug Information Service. Copyright 2014, Drug Information Service, University of Utah, Salt Lake City, UT.