Reported Adverse Drug Reaction of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension in the Pediatrics with Congenital Heart Disease
Keywords:
pulmonary arterial hypertension; sildenafil; pediatrics; congenital heart disease; safetyAbstract
Background and objective: Sildenafil has been used off-label for treatment pulmonary arterial hypertension associated with congenital heart disease (APAH-CHD) in pediatric patients but it is not approved by United States Food and Drug Administration (USFDA) and Thai Food and Drug Administration in the pediatric population. Thus, this study aimed to investigate the adverse drug reactions of sildenafil for the treatment of APAH-CHD in pediatric patients.
Methods: This study was a retrospective study in children under 18 years old with APAH-CHD who receiving sildenafil treatment at Queen Sirikit Heart Center of the Northeast, Khon Khan University during January 2009 to December 2014. Adverse drug reactions, duration of treatment and dosing of sildenafil data were collected by chart review.
Results: There were 112 patients included in the study. There were 8 patients (7.1%) with 8 adverse drug events reported during the treatment period, headache in 5 patients and epistaxis in 3 patients.
Conclusions: The use of sildenafil seems to be safe in the treatment of APAH-CHD in children under 18 years old. The common ADRs were headache and epistaxis without any serious adverse event reported.
References
2. Van Loon RLE, Roofthooft MTR, Hillege HL, ten Harkel ADJ, van Osch-Gevers M, Delhaas T, et al. Pediatric pulmonary hypertension in The Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation 2011; 124: 1755–64.
3. U.S.Food and Drug Administration. REVATIO (sildenafil) label. [cited Feb 5, 2015]. Available from:http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021845s011,022473s004,0203109s002lbl.pdf
4. Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 2012; 125: 324–34.
5. Barst RJ, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M, et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation 2014; 129: 1914–23.
6. U.S. Food and Drug Administration. FDA drug safety communication: FDA recommends against use of Revatio (sildenafil) in children with pulmonary hypertension [8-30-2012]. [cited Feb5, 2015]. Available from:http://www.fda.gov/Drugs/DrugSafety/ucm317123.htm.
7. FDA drug safety communication: FDA clarifies warning about pediatric use of Revatio (sildenafil) for pulmonary arterial hypertension[3-31-2014]. [cited Feb5,2015]. Available from:http://www.fda.gov/Drugs/DrugSafety/ucm390876.htm
8. Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, et al. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo controlled, crossover trial. Circulation 2011; 123: 1185-93.
9. Humpl T, Reyes JT, Holtby H, Stephens D, Adatia I. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111: 3274–80.
10. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148–57.
11. Ferrari A. Headache: One of the most common and troublesome adverse reactions to drugs. Curr Drug Safety 2006; 1: 43–58.
12. Ferrari A, Spaccapelo F, Gallesi D, Sternieri E. Focus on headache as an adverse reaction to drugs. J Headache Pain 2009; 10: 235–9.
13. Rondina MT, Weyrich AS. Targeting Phosphodiesterases in Anti-platelet Therapy. Handb Exp Pharmacol 2012; 210: 225-38.
14. Gresele P, Momi S, Falcinelli E. Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 2011; 72: 634-46.
15. European Medicines Agency. Assessment report for Revatio. International non-proprietary name: sildenafil. Procedure No. EMEA/H/C/000638/II/0028.London, UK: European Medicines Agency; 2011 [cited Feb5ม 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000638/WC500107804.pdf.
16. The Heart Association of Thailand under the Royal Patronage of His Majesty the King. Guideline for diagnosis and treatment of pulmonary hypertension 2013. 2nd ed. Bangkok: Colour Harmony Co.Ltd.; 2013.
17. Joint Formulary Committee. British National Formulary for Children. 2011–2012. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2011.
