Infants and Children’s Acetaminophen

The American Academy of Pediatrics, U.S. FDA, and Australian TGA among other health agencies, recommend to dose acetaminophen to a child’s weight, then alternatively to age only if weight is not known.¹ Dosage of acetaminophen based on a child weight and/or body surface area, is recognized as the most accurate basis for calculating the optimal drug dosage.²

This optimal weight-based dosing has been validated through dozens of clinical studies. This data has been published since 1976, including by the leading brand producer of acetaminophen in the U.S. by clinical submissions to the FDA in 2009.³

Conversely, no oral delivery applicators included within acetaminophen products have a weight and age indicia.

Studies and statistical data continue to corroborate the leading causes of medication error during the administration of children’s and infants’ acetaminophen. The most common errors stem from an incorrect dose primarily associated from the correlation between the dosing applicator and the medication instructions and/or packaging.⁴

Further exacerbating potential dosing errors, the current U.S mL dosing regimen provides highly variable dosing to sensitive small mass pediatric patients. For example, the current mL dosing provides the lowest weight and youngest patients (24lb at 24 months), the near maximum dose of 6.67 mg/lb (14.70 mg/kg), and the heaviest weight and oldest patient (35 lb at 36 months) in the same range, receiving the lowest possible dose of 4.57mg/lb (10.07 mg/kg).⁵  More specifically, FDA submissions and original supporting clinical safety and efficacy studies identify the optimal dosing at 12.5mg/kg, and clearly demonstrate the extreme limits provided by this dosing regimen while attempting to control the dose between the 10-15mg/kg range.⁵

This highly variable dosing continues to be US industry practice, although the original 1983 weight-based dosing schedule published was intended to provide increases in dose corresponding with incremental increases in weight”.⁶  That study highlighted this weight-based dosing regimen to provide a more consistent mg/kg dosing pattern.⁶

More importantly, the original safety and efficacy studies published for the approval of infants’ and children’s acetaminophen; clearly demonstrate the minimum effective dose at a fixed unit dose of 10mg/kg (4.54mg/lb), and not as a variable range dose.^6,7 In addition, one of the largest pediatric drug trials ever conducted, and regarded pivotal for the pediatric approval of acetaminophen, was completed and its results published utilizing a fixed unit dose of 12mg/kg.⁸

^1] United States Food and Drug Administration. Meeting of the Nonprescription Drugs Advisory Committee. May 17-18, 2011. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM264148.pdf
^2] Zenk KE,(1979): Drug dosing in children. In Pagliaro LA, Levin RH (eds):“Problems in Pediatric Drug Therapy”. Drug Intelligence Pub, Inc. pp 209-219
^3] Rane A. Wilson JT (1976): Clinical pharmacokinetics in infants and children. Clin Pharmacokin 1:2-24
^4] Hurwitz J, Sands S, Davis E, Nielsen J, Warholak T. Patient knowledge and use of acetaminophen in over-the-counter medications. J Am Pharm Assoc (2003)
^5] Tylenol^® Infants and Children’s Dosing Information for Healthcare. https://www.tylenol.com/children-infants/safety/dosage-charts McNeil Consumer Healthcare.
^6] FDA Citizen Petition February 1,1999. https://ia600405.us.archive.org/29/items/607305-19 99-mcneil-citizen-petition-on-pediatrics/607305-1999-mcneil- citizen-petition-on-pediatrics.pdf
^7] Temple, A.R., “Pediatric dosing of acetaminophen”. Pediatric Pharmacology 1983; 3:321-327
^8] Boston University Fever Study. 1994 http://www.bu.edu/slone/research/scor-network/

¹] Simon, H. K., & Weinkle, D. A. (1997). Over-the-counter medications: do parents give what they intend to give? Archives of pediatrics & adolescent medicine, 151(7), 654-656.
²] Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Heard SE. 2007 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). 2008; 46(10):927-1057.

¹] Tylenol^® Infants and Children’s Dosing Information for Healthcare Professionals
²] Adjusted for U.S. Market and mL dosing conformity – (Safe-2-Dose™ Optimal Dose of 12.5mg/kg (5.67 mg/lb.) to 10.14mg/kg (4.60 mg/lb.))
³] US Food and Drug Administration – Over the counter Acetaminophen –Containing Drug Products in Children Background Package – Efficacy and Safety Studies published and reviewed at 4.54 mg/lb. to 6.80 mg/lb. Publish Studies mid-point and Safe-2-Dose™ Optimal Recommended Dose 5.67 mg/lb.
⁴] American Academy of Pediatric Endorses Weight Based Dosing – Recommended Dosing at 4.54 mg/lb. to 6.80 mg/lb. mid-point and Safe-2-Dose™ Optimal Recommended Dose 5.67 mg/lb.

Tylenol^® is a registered trademark of Johnson & Johnson.

To promote dosing accuracy, both the American Academy of Pediatrics (AAP) and the US Food and Drug Administration (FDA) recommend that parents use dosing tools that are paired with the specific medication.

Oral syringes are considered the gold standard when accuracy is critical.1 Nevertheless, Dosing cups are the most frequently included dosing devices included with OTC medications.

Studies have shown a >4 times increase of error when dosing cups are use verses syringes.1

Nevertheless, due to the increase in volume of the medication required for Children verses Infants; as well as perhaps user preference, syringes are mainly utilized for infants’ administration.

The Safe-2-Dose™ is designed to provide the safety and accuracy of an oral syringe while offering the convenience of a spoon or dosing cup. The Safe-2-Dose™ is calibrated to the dosage strength and marked with multiple correlated indicia measurements. These measurements may include, among others, weight or other patient characteristic, medication dosage or volume of the medication. The enhanced multi-indicia display increases the overall safety and accuracy of administration, by providing the ability to intuitively correlate the unit dosage to a specific patient characteristic.

¹] Yin HS, Parker RM,Sanders LM, et al. Liquid Medication Errors and Dosing Tools: A Randomized Control Experiment. Pediatrics 2016;138(4):e20160357
²] Tylenol® Infants and Children’s Dosing Information for Healthcare Professionals
³] Adjusted for U.S. Market and mL dosing conformity – (Safe-2-Dose™ Optimal Dose of 12.5mg/kg (5.67 mg/lb.) to 12.41mg/kg (5.63 mg/lb.))
⁴] US Food and Drug Administration – Over the counter Acetaminophen –Containing Drug Products in Children Background Package – Efficacy and Safety Studies published and reviewed at 4.54 mg/lb. to 6.80 mg/lb. Publish Studies mid-point and Safe-2-Dose™ Optimal Recommended Dose 5.67 mg/lb.
⁵] American Academy of Pediatric Endorses Weight Based Dosing – Recommended Dosing at 4.53 mg/lb. to 6.80 mg/lb. mid-point and Safe-2-Dose™ Optimal Recommended Dose 5.67 mg/lb.

Tylenol^® is a registered trademark of Johnson & Johnson.

The Safe-2-Dose^® is a registered trademark of Asepsis Medical Technologies, LLC., and covered by one or more patents, including; US Patent 11,517,505 and Patents Pending.