Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 29:14:229-248.
doi: 10.2147/JPR.S269530. eCollection 2021.

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

Ayman Eissa  1 , Eva Tarau  2 , Christoph Beuter  3 , Tatjana Radic  3 , Estelle Watson  3 , Melanie Sohns  3 , Claudia Lefeber  3 , Gregory B Hammer  4
Affiliations

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

Ayman Eissa et al. J Pain Res. .

Abstract

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.

Keywords: infants; intravenous formulation; neonates; oral formulation; pain management; tapentadol.

PubMed Disclaimer

Conflict of interest statement

AE and GBH were investigators on the clinical trials published here and were paid by Grünenthal GmbH for their contributions to these trials. ET was an employee of Grünenthal USA Inc. at the time the trials were conducted. EW was an employee of Grünenthal GmbH at the time the trials were conducted. All other authors are current employees of Grünenthal GmbH. The authors report no other potential conflicts of interest for this work.

Figures

Figure 1
Figure 1
Dose finding process for tapentadol oral solution and intravenous infusion for the age range preterm neonates to children <18 years of age.
Figure 2
Figure 2
Tapentadol serum concentrations in young infants <2 years of age following a single dose of tapentadol oral solution (overlaid with adult simulated exposures).
Figure 3
Figure 3
Mean pain intensity over time scored with the observational Face, Legs, Activity, Cry, and Consolability scale (A) following a single dose of tapentadol oral solution, (B) following a single dose of intravenous tapentadol, (C) prior to each intake of tapentadol oral solution (first seven intakes, multiple dose trial).
Figure 4
Figure 4
Individual tapentadol serum concentration-time profiles following a single dose of intravenous tapentadol.
Figure 5
Figure 5
Individual tapentadol serum concentration-time profiles following single dose administrations of oral tapentadol solution or an intravenous tapentadol infusion. Figure includes the data of children ≥2 years.,
See this image and copyright information in PMC

References

    1. Wilson CA, Sommerfield D, Drake-Brockman TFE, Lagrange C, Ramgolam A, von Ungern-Sternberg BS. A prospective audit of pain profiles following general and urological surgery in children. Paediatr Anaesth. 2017;27:1155–1164. doi: 10.1111/pan.13256 - DOI - PubMed
    1. Groenewald CB, Rabbitts JA, Schroeder DR, Harrison TE. Prevalence of moderate-severe pain in hospitalized children. Paediatr Anaesth. 2012;22:661–668. doi: 10.1111/j.1460-9592.2012.03807.x - DOI - PubMed
    1. Ranger M, Grunau RE. Early repetitive pain in preterm infants in relation to the developing brain. Pain Manag. 2014;4(1):57–67. doi: 10.2217/pmt.13.61 - DOI - PMC - PubMed
    1. Fitzgerald M, Walker SM. Infant pain management: a developmental neurobiological approach. Nat Clin Pract Neurol. 2009;5(1):35–50. doi: 10.1038/ncpneuro0984 - DOI - PubMed
    1. Beggs S. Long-term consequences of neonatal injury. Can J Psychiatry. 2015;60(4):176–180. doi: 10.1177/070674371506000404 - DOI - PMC - PubMed

LinkOut - more resources