September 12, 2012

FDA Issues Warning on Off-Label
Use of Sildenafil in Children

Washington, D.C.—Revatio (sildenafil) should not be prescribed off-label to children with pulmonary arterial hypertension, according to the FDA, because of the greater risk of death in high doses and little effectiveness in low doses. The label is being changed to reflect the new warning.

The FDA action was based on a long-term clinical pediatric trial which indicated an inflated risk of death in subjects taking high doses and little improvement in exercise ability in subjects taking low doses.

Revatio, marketed in the United States by Pfizer, is a phosphodiesterase-5 inhibitor used to treat pulmonary arterial hypertension (PAH) by relaxing the blood vessels in the lungs to reduce blood pressure. It is FDA-approved at 20 mg three times a day to improve exercise ability and delay clinical worsening of PAH in adult patients, but not in patients 17 years old and younger.

The FDA advises that the parents or caregivers should not change Revatio dosage or have children stop taking the drug without consulting a health care provider. It also reminded prescribers that “use of this product, particularly chronic use, in children is an off-label indication, not approved by FDA, and is not recommended.”

The randomized, double-blind, placebo-controlled clinical trial cited by the FDA involved 234 children with mild-to-moderate PAH at baseline. Over 3 years of follow-up, the hazard ratio for death among those receiving high doses of sildenafil was 3.5, usually caused by heart failure or pulmonary hypertension.

The 16-week trial of subjects 1- to 17-years old, who received sildenafil three times a day based on body weight, also showed no improvement in exercise capacity, which was the primary endpoint.

Although sildenafil is marketed at different dosages as Viagra, the safety concerns do not apply to that erectile dysfunction drug “given the differences in patient population and the different recommended dosing regimens,” the FDA said.

U.S. Pharmacist Social Connect