Pediatric Cardiology

, Volume 33, Issue 5, pp 683–688 | Cite as

Initial Experience With Tadalafil in Pediatric Pulmonary Arterial Hypertension

  • Shinichi Takatsuki
  • Michelle Calderbank
  • David Dunbar Ivy
Original Article


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.


Children Phosphodiesterase type 5 inhibitor Safety Sildenafil Tadalafil Tolerability 


  1. 1.
    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 41:2119–2125PubMedCrossRefGoogle Scholar
  2. 2.
    Chin KM, Rubin LJ (2008) Pulmonary arterial hypertension. J Am Coll Cardiol 51:1527–1538PubMedCrossRefGoogle Scholar
  3. 3.
    Eli Lilly and Company. ADCIRCA (tadalafil) tablets for oral administration: U.S. prescribing information. Retrieved Oct 2009 at
  4. 4.
    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 353:2148–2157PubMedCrossRefGoogle Scholar
  5. 5.
    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 114:48–54PubMedCrossRefGoogle Scholar
  6. 6.
    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 119:2894–2903PubMedCrossRefGoogle Scholar
  7. 7.
    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 111:3274–3280PubMedCrossRefGoogle Scholar
  8. 8.
    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 99:696–698PubMedCrossRefGoogle Scholar
  9. 9.
    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 51:161–169PubMedCrossRefGoogle Scholar
  10. 10.
    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 106:1332–1338PubMedCrossRefGoogle Scholar
  11. 11.
    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 158:584–588PubMedCrossRefGoogle Scholar
  12. 12.
    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 114:1807–1810PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenzweig EB (2010) Tadalafil for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 11:127–132PubMedCrossRefGoogle Scholar
  14. 14.
    Rubin LJ (1997) Primary pulmonary hypertension. N Engl J Med 336:111–117PubMedCrossRefGoogle Scholar
  15. 15.
    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–e855Google Scholar
  16. 16.
    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 507–499CrossRefGoogle Scholar
  17. 17.
    Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ (2004) Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 110:660–665PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Shinichi Takatsuki
    • 1
  • Michelle Calderbank
    • 1
  • David Dunbar Ivy
    • 1
  1. 1.Division of Pediatric Cardiology, Department of PediatricsChildren’s Hospital Colorado University of Colorado School of MedicineAuroraUSA

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