FDA Clarifies Warning about Sildenafil Pediatric Use for PAH


Editors:

Elham Reshid and Hailemariam Shimelis

Sildenafil (Revatio) is a phosphodiesterase-5 (PDE-5) inhibitor indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability by relaxing the blood vessels in the lungs to reduce blood pressure and delay clinical worsening. It is also marketed in the prescription product Viagra, a drug for adult males with erectile dysfunction (inability to get or maintain an erection).

Comparison of Pulmonary Hypertension and Normal Heart

Comparison of Pulmonary Hypertension and Normal HeartFor the treatment of PAH, Sildenafil is FDA-approved only in adults and has never been approved for the treatment of PAH in children by FDA. But off-label use of the drug in pediatric patients is practiced by health care providers. Hence, FDA revised the Sildenafil drug label in August 2012, adding a warning stating that “use of Sildenafil, particularly chronic use, is not recommended in children.”

This recommendation was based on a long-term randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging clinical trial in pediatric patients with PAH.

In this trial, a direct dose-related effect on mortality was observed with the highest dose having the worst outcome. The hazard ratio for high dose compared to low dose was 3.5 (p=0.015). Deaths were first observed after about 1 year, and then occurred at fairly constant rates within each group. Causes of death were typical of patients with pulmonary hypertension.

Children taking a high dose of Sildenafil had a higher risk of death than chil-dren taking a low dose and The low doses of Sildenafil are not effective in improving exercise ability.

In light of these risks, the use of Sildenafil is not recommended by FDA in children. This recommendation was not intended to suggest that Sildenafil should never be used in children; however, some health care professionals have interpreted this information as a contraindication, and have refused to pre-scribe or administer the drug.

Following this FDA has clarified its previous recommendation related to prescribing Sildenafil for children with PAH.

The evidence behind FDAs initial recommendation has not changed however, health care professionals must consider whether the benefits of treatment with the drug are likely to outweigh its potential risks for each patient. There may be situations in which the benefit-risk profile of Sildenafil may be acceptable in individual children, for example, when other treatment options are limited and Sildenafil can be used with close monitoring.

 To download the article in pdf click here

References:

http://www.fda.gov/drugs/drugsafety/ucm317123.htm

http://www.fda.gov/Drugs/DrugSafety/ucm390876.htm

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedical-Products/ucm391152.htm

http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021845s011,022473s004,0203109s002lbl.pdf

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