Acetaminophen, Ibuprofen Often Under-Dosed in Children in the ED

Acetaminophen and ibuprofen are frequently under-dosed in children in the emergency department, according to a study published in the European Journal of Pediatrics.¹

Gregorio P. Milani from the University of Milan, Italy and colleagues analyzed data from 17 Italian hospitals that included 1471 children (age 4 weeks to 14 years) between January 2013 and October 2014 who presented to the emergency department with pain. (Clinical trial registration: Agenzia Italiana del Farmaco–Observational Study Register; Registration code, PIERRE/1).

Adequate doses of pain medication in pediatric patients are as follows:

• Oral acetaminophen: 15-20 mg/kg body weight (1 g in children ≥50 kg body weight)
• Rectal acetaminophen: 30-40 mg/kg body weight
• Intravenous acetaminophen 7.5 mg/kg body weight (15 mg/kg in children ≥10 kg)
• Oral ibuprofen: 10 mg/kg body weight (400 mg in children ≥40 kg body weight)

Of the 1471 children, 518 were prescribed the appropriate dose, 60 were prescribed an excessive dose by ≤10%, and 893 were prescribed an insufficient dose (61% of cases).

Of the children prescribed an insufficient dose, 577 children were prescribed acetaminophen (57.7% boys; median age, 6; age range, 2 to 10.5), and 316 children were prescribed ibuprofen (59.8% boys; median age, 5.8; age range, 2 to 10) .

The percentage of variation from the minimum appropriate dose was on average equal for oral and intravenous acetaminophen (20%), but was significantly higher for rectal acetaminophen (47%, P <.001) and oral ibuprofen (30%, P <.05).

“In this study, under-dosing occurred significantly more often in children prescribed [with] rectal acetaminophen and oral ibuprofen. The lack of available adequate formulations likely accounts for under-dosing of the former,” the researchers wrote.

Under-dosing of oral ibuprofen may stem from concerns regarding toxicity from non-steroidal anti-inflammatory agents.²

“Patients weighing <12 kg or >40 kg were also prescribed under-dosage of acetaminophen and ibuprofen,” they noted. A similar tendency was observed in a previous study of children prescribed antimicrobials and opioids.³

Summary & Clinical Applicability

These findings indicate that more than 60% of children presenting to Italian emergency departments with acute pain are prescribed an insufficient dose of acetaminophen or ibuprofen.

“The similar prevalence of dose errors in both pediatric and general centers with and without internal guidelines for acute pain management confirms that physicians often do not adhere to guidelines based on review of evidence-based medicine. Poor awareness or familiarity with guidelines account at least in part for this observation,” the researchers wrote.

They also noted that in addition to pain, acetaminophen and ibuprofen are often prescribed for managing fever.⁴ “Currently recommended dosing regimens are lower by 30% or more when treating fever as compared to pain. Hence, we speculate that the prescription of insufficient doses of these drugs for acute pain management may reflect, in many cases, prescription of anti-pyretic doses,” they wrote.

The researchers concluded that defining clinical practice guidelines on acute pain management for children is only the first step in developing evidence-based care. “An appropriate next step is to devise effective methods for their implementation emphasizing that recommended doses of acetaminophen and ibuprofen are different when managing fever or pain.”

Limitations & Disclosures

• This study only considered weight-based regimens, while in some circumstances other methods for scaling dosage might be more appropriate (eg, excessive body mass index). 
• These findings are limited to the prescribing stage and do not consider possible errors in dispensing medication.

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References

1. Milani GP, Benini F, Dell’Era L, et al; PIERRE GROUP STUDY. Acute pain management: acetaminophen and ibuprofen are often under-dosed. Eur J Pediatr. 2017;176(7):979-982. doi:10.1007/s00431-017-2944-6
2. Misurac JM, Knoderer CA, Leiser JD, Nailescu C, Wilson AC, Andreoli SP. Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children. J Pediatr. 2013;162:1153-1159.
3. Miller JL, Johnson PN, Harrison DL, Hagemann TM. Evaluation of inpatient admissions and potential antimicrobial and analgesic dosing errors in overweight children. Ann Pharmacother. 2010;44:35-42.
4. Marzuillo P, Guarino S, Barbi E. Paracetamol: a focus for the general pediatrician. Eur J Pediatr. 2014;173:415-425.