Abstract
This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m2; p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.
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References
Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, Wasserman K, Oudiz R, Shapiro S, Robbins IM, Channick R, Badesch D, Rayburn BK, Flinchbaugh R, Sigman J, Arneson C, Jeffs R (2003) Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 41:2119–2125
Chin KM, Rubin LJ (2008) Pulmonary arterial hypertension. J Am Coll Cardiol 51:1527–1538
Eli Lilly and Company. ADCIRCA (tadalafil) tablets for oral administration: U.S. prescribing information. Retrieved Oct 2009 at http://www.drugs.com/newdrugs/fda-approves-adcirca-tadalafil-pulmonary-arterial-hypertension-1366.html
Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353:2148–2157
Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M (2006) Bosentan therapy in patients with eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 114:48–54
Galiè N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ (2009) Tadalafil therapy for pulmonary arterial hypertension. Circulation 119:2894–2903
Humpl T, Reyes JT, Holtby H, Stephens D, Adatia I (2005) Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 111:3274–3280
Ivy DD, Claussen L, Doran A (2007) Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. Am J Cardiol 99:696–698
Ivy DD, Doran AK, Smith KJ, Mallory GB Jr, Beghetti M, Barst RJ, Brady D, Law Y, Parker D, Claussen L, Abman SH (2008) Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol 51:161–169
Ivy DD, Rosenzweig EB, Lemarie JC, Brand M, Rosenberg D, Barst RJ (2010) Long-term outcomes in children with pulmonary arterial hypertension treated with bosentan in real-world clinical settings. Am J Cardiol 106:1332–1338
Levy M, Celermajer DS, Bourges-Petit E, Del Cerro MJ, Bajolle F, Bonnet D (2011) Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr 158:584–588
Mukhopadhyay S, Sharma M, Ramakrishnan S, Yusuf J, Gupta MD, Bhamri N, Trehan V, Tyagi S (2006) Phosphodiesterase-5 inhibitor in eisenmenger syndrome: a preliminary observational study. Circulation 114:1807–1810
Rosenzweig EB (2010) Tadalafil for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 11:127–132
Rubin LJ (1997) Primary pulmonary hypertension. N Engl J Med 336:111–117
Singh TP, Rohit M, Grover A, Malhotra S, Vijayvergiya R (2006) A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am Heart J 151(851):e851–e855
von Keitz A, Rajfer J, Segal S, Murphy A, Denne J, Costigan T, Lockhart D, Beasley CM Jr, Emmick JT (2004) A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil. Eur Urol 45:499–507 discussion 507–499
Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ (2004) Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 110:660–665
Acknowledgment
This study was supported by the Jayden DeLuca Foundation, the Leah Bult Foundation, the UL1 RR025780 Colorado Clinical Translational Science Institute, the National Center for Research Resources, and the National Institutes of Health.
Disclosure
The University of Colorado is paid by United Therapeutics and Pfizer for Dr. Ivy to be a consultant.
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Takatsuki, S., Calderbank, M. & Ivy, D.D. Initial Experience With Tadalafil in Pediatric Pulmonary Arterial Hypertension. Pediatr Cardiol 33, 683–688 (2012). https://doi.org/10.1007/s00246-012-0180-4
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DOI: https://doi.org/10.1007/s00246-012-0180-4