The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG
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J Pediatr Pharmacol Ther · Jan 2020
Evaluating the Transition From Dexmedetomidine to Clonidine for the Prevention of Withdrawal in Critically Ill Pediatric Patients.
To evaluate clonidine for preventing withdrawal from dexmedetomidine infusions and describe the incidence of withdrawal symptoms and adverse cardiovascular effects in critically ill pediatric patients. ⋯ Patients receiving prolonged infusions of dexmedetomidine may transition to clonidine to help prevent withdrawal symptoms. Duration of dexmedetomidine infusion of 7 days or longer and higher average dexmedetomidine dose 24 hours prior to the transition are important considerations when determining the initial clonidine dose. Transition from dexmedetomidine to clonidine was found to be safe and efficacious in our patients, with minimal adverse effects.
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J Pediatr Pharmacol Ther · Jan 2020
ReviewElexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy.
Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulating therapy that contains 2 correctors and a potentiator of the CFTR channel. Its labeled indication for use is for persons 12 years of age and older with at least 1 F508del mutation for the CFTR gene. This drug combination provides potential therapy to many patients who had previously been excluded from CFTR modulation therapy due to the nature of their genetic mutations. ⋯ The most common adverse events seen in clinical trials included rash and headache, and laboratory monitoring is recommended to evaluate liver function. Continued evaluation of patient data is needed to confirm its long-term safety and efficacy. Elexacaftor-tezacaftor-ivacaftor is a monumental and encouraging therapy for cystic fibrosis; however, approximately 10% of the CF population are not candidates for this or any other CFTR modulation therapy.
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J Pediatr Pharmacol Ther · Jan 2020
Case ReportsPharmacokinetics, Efficacy and Safety of Bosutinib in a Pediatric Patient With Chronic Myeloid Leukemia.
Bosutinib is a second-generation tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia (CML) in adult patients. The safety and efficacy of bosutinib in patients younger than 18 years of age have not been established. We here report the case of a 4-year-old male with CML who was treated with bosutinib during coordination of human leukocyte antigen-matched unrelated bone-marrow transplantation because of insufficient responses to imatinib and dasatinib. ⋯ At steady state, maximum plasma concentration, minimum plasma concentration, and area under the plasma concentration-time curve were 89.2 ng/mL, 16.7 ng/mL, and 1017.4 ng·hr/mL, respectively, at 290 mg/m2/day; and 141.1 ng/mL, 18.9 ng/mL, and 1278.5 ng·hr/mL, respectively, at 330 mg/m2/day. To the best of our knowledge, this is the first case report to show the pharmacokinetics of bosutinib with efficacy and safety in a pediatric patient with CML. This rare case in a very young child with CML can also be valuable reference for clinical practice.
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J Pediatr Pharmacol Ther · Jul 2019
Effects of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on the Sequestration of Mycophenolate Mofetil, Tacrolimus, Hydromorphone, and Fentanyl.
With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. ⋯ Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.
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J Pediatr Pharmacol Ther · May 2019
ReviewNusinersen: A Novel Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) encompasses a group of autosomal recessively inherited degenerative neuromuscular disorders. They range in severity from neonatal onset with rapidly progressive weakness and early mortality (SMA-1), to onset in infancy (SMA-2), to adolescent/adult onset with indolent clinical course (SMA-3/-4). SMA patients share mutations in the survival motor neuron (SMN) gene; variations in clinical phenotypes are attributable to copy numbers of the closely related SMN2 gene. ⋯ Treatment requires complex financial and logistics because of the very high drug cost, intrathecal administration, and medical fragility of the patients. Treatment implementation also engenders ethical considerations related to cost, insurance coverage, limited clinical data on groups of patients not in clinical trials, and questions of duration of treatment. Nusinersen has been integrated into the treatment of many SMA patients.