&lt;p&gt;Population Pharmacokinetics of Tapentadol in Children from Birth to &lt;18 Years Old&lt;/p&gt;

Khalil, Feras; Choi, Siak Leng; Watson, Estelle D.; Tzschentke, Thomas; Lefeber, Claudia; Eerdekens, Mariëlle; Freijer, Jan

doi:10.2147/jpr.s269549

Cited by 7 publications

(16 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The data were instead incorporated into a population PK model developed in older children; 25 this updated model is described in a recent publication. 27 …”

Section: Discussionmentioning

confidence: 99%

“…The serum concentration data of both trials were included in a POP-PK model. 27 Due to the sparseness of data, formal non-compartmental analysis could not be performed.…”

Section: Methodsmentioning

confidence: 99%

“…Hence, to determine appropriate doses for the phase 3 trial, the PK data from the single dose trial were incorporated into a POP-PK model. 27 Simple PK analysis using for example a noncompartmental approach is not appropriate for sparsely sampled trials.

Figure 1 Dose finding process for tapentadol oral solution and intravenous infusion for the age range preterm neonates to children <18 years of age.…”

Section: Introductionmentioning

confidence: 99%

“…22 Detailed information about the program and the trials can be found in the thematic pediatric tapentadol series in this journal. 9,[23][24][25][26][27][28] Whereas efficacy and safety of tapentadol OS have been demonstrated for older pediatric patients, 26 the PK profile, efficacy, and safety in patients <2 years have so far not been published. In order to investigate efficacy and safety of tapentadol OS for the treatment of acute moderate-to-severe postsurgical pain in children <2 years, a phase 3, randomized, double-blind, placebo-controlled, multiple dose efficacy and safety trial was required.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tapentadol for the Treatment of Moderate-to-Severe Acute Pain in Children Under the Age of Two Years

Eissa

Tarau²,

Beuter

et al. 2021

JPR

Self Cite

View full text Add to dashboard Cite

Background Pharmacokinetics (PK), efficacy, and safety of the opioid analgesic tapentadol in the treatment of moderate-to-severe acute pain have so far not been investigated in pediatric patients <2 years of age. Patients and Methods Two multicenter, open-label trials assessed the pharmacokinetic profile, safety, tolerability, and efficacy of single doses of tapentadol oral solution (OS; NCT02221674; n=19) or intravenous infusion (IV, EudraCT 2014-002259-24; n=38) in children from birth to <2 years of age. Of these, 8 preterm neonates were included in the IV trial. A third randomized, double-blind, placebo-controlled trial (NCT02081391) investigated the efficacy and safety of multiple tapentadol OS doses in patients from birth to <2 years (placebo n=4, tapentadol n=11) using an immediate rescue trial design. Patients in all three trials underwent surgery that, in the investigator’s opinion, reliably produced moderate-to-severe pain requiring opioid treatment. Results Administration of single tapentadol doses resulted in tapentadol serum concentrations within the targeted range known to be safe and efficacious in adults and compared well to the range observed for children aged 2 to <18 years. Pain intensity already improved 15 min after administration. In the multiple dose trial, amounts of supplemental opioid analgesic medication within the first 24 h after start of trial medication were low (placebo 0.02 mg/kg, tapentadol 0.05 mg/kg). All patients stopped treatment with the trial medication because opioid analgesics were no longer required. Treatment-emergent adverse events occurred in 42.1% (tapentadol OS single dose), 28.9% (tapentadol IV), and 75% of placebo and 54.5% of tapentadol patients (tapentadol OS multiple doses), none of them serious. Conclusion Tapentadol showed a favorable PK and safety profile in children <2 years of age. Multiple tapentadol OS dosing is efficacious and generally well tolerated in children ≥2 years and might also be a useful treatment option for children <2 years in need of strong analgesics.

show abstract

“…The data were instead incorporated into a population PK model developed in older children; 25 this updated model is described in a recent publication. 27 …”

Section: Discussionmentioning

confidence: 99%

“…The serum concentration data of both trials were included in a POP-PK model. 27 Due to the sparseness of data, formal non-compartmental analysis could not be performed.…”

Section: Methodsmentioning

confidence: 99%

Figure 1 Dose finding process for tapentadol oral solution and intravenous infusion for the age range preterm neonates to children <18 years of age.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tapentadol for the Treatment of Moderate-to-Severe Acute Pain in Children Under the Age of Two Years

Eissa

Tarau²,

Beuter

et al. 2021

JPR

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, extensive PK profiling supported by modelling and simulation techniques took place to address all age groups and all tapentadol formulations used in this program and to determine the doses used in the efficacy trials. 16 , 17 …”

Section: Efficacy and Safety Of Tapentadol In The Pediatric Populatiomentioning

confidence: 99%

Outcomes of the Pediatric Development Plan of Tapentadol

Eerdekens

Radic

Sohns

et al. 2021

JPR

Self Cite

View full text Add to dashboard Cite

The opioid analgesic tapentadol was the first pain medication to be developed for the treatment of pain in children under a formal process established by the regulatory authorities. This article summarizes the outcomes of the pediatric development program for tapentadol across the entire age range from birth (including neonates) to adolescents <18 years of age. In addition, the challenges experienced when designing and conducting the pediatric tapentadol clinical trials as well as the interactions with the regulatory authorities are discussed. As a first outcome, the oral solution of tapentadol was authorized in the EU in 2018 as a new treatment option in the hospital setting for moderate to severe acute pain in children from 2 to <18 years of age.

show abstract