Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience
IntroductionPhosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1055131/full |
| _version_ | 1797942779709489152 |
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| author | David Edward Youssef Stephanie S. Handler Susan Marjorie Richards Catherine Anne Sheppard Jenna Smith Kathryn Tillman Matthew Pietrosanu Edward Kirkpatrick Angela Bates Angela Bates |
| author_facet | David Edward Youssef Stephanie S. Handler Susan Marjorie Richards Catherine Anne Sheppard Jenna Smith Kathryn Tillman Matthew Pietrosanu Edward Kirkpatrick Angela Bates Angela Bates |
| author_sort | David Edward Youssef |
| collection | DOAJ |
| description | IntroductionPhosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH).Methods and materialsThis is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation.ResultsOver the study period, 154 children with a median age of 1.0 (range 0.0–6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients.ConclusionTadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means. |
| first_indexed | 2024-04-10T20:14:00Z |
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| id | doaj.art-e887eece9e8748d6a1fef97eea55f9c4 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-10T20:14:00Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-e887eece9e8748d6a1fef97eea55f9c42023-01-26T08:06:53ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-01-011110.3389/fped.2023.10551311055131Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experienceDavid Edward Youssef0Stephanie S. Handler1Susan Marjorie Richards2Catherine Anne Sheppard3Jenna Smith4Kathryn Tillman5Matthew Pietrosanu6Edward Kirkpatrick7Angela Bates8Angela Bates9Division of Pediatrics, Department of Pediatric Pulmonary Hypertension, Stollery Children's Hospital, Edmonton, AB, CanadaDivision of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Pediatrics, Department of Pediatric Pulmonary Hypertension, Stollery Children's Hospital, Edmonton, AB, CanadaDivision of Pediatrics, Department of Pediatric Pulmonary Hypertension, Stollery Children's Hospital, Edmonton, AB, CanadaDepartment of Pharmacy, Stollery Children's Hospital, Edmonton, AB, CanadaDivision of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, CanadaDivision of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Pediatrics, Department of Pediatric Pulmonary Hypertension, Stollery Children's Hospital, Edmonton, AB, CanadaDivision of Pediatric Critical Care, Division of Pediatrics, University of Alberta, Edmonton, AB, CanadaIntroductionPhosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH).Methods and materialsThis is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation.ResultsOver the study period, 154 children with a median age of 1.0 (range 0.0–6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients.ConclusionTadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.https://www.frontiersin.org/articles/10.3389/fped.2023.1055131/fulladverse effectechocardiographyhemodynamicpulmonary vasodilatorsafetytolerability |
| spellingShingle | David Edward Youssef Stephanie S. Handler Susan Marjorie Richards Catherine Anne Sheppard Jenna Smith Kathryn Tillman Matthew Pietrosanu Edward Kirkpatrick Angela Bates Angela Bates Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience Frontiers in Pediatrics adverse effect echocardiography hemodynamic pulmonary vasodilator safety tolerability |
| title | Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience |
| title_full | Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience |
| title_fullStr | Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience |
| title_full_unstemmed | Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience |
| title_short | Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience |
| title_sort | multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension a north american experience |
| topic | adverse effect echocardiography hemodynamic pulmonary vasodilator safety tolerability |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1055131/full |
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