Back to the Top
Does anyone have information about possible hepato-toxicity of APAP when it is
given at the recommended dosage to infants?
Thanks
Scott
Date: Fri, 14 Aug 1998 17:44:17 -0500
From:(by way of David_Bourne)
Subject: Pharmacodynamics: Children vs. Adults
I am conducting literature research on pharmacodynamics in the
children population. Would someone please explain the difference(s),
if any, in the children vs. the adult populations. Is it unique in
children?
Thank you.
Vivian Nolan
Back to the Top
[A couple of replies -db]
Date: Fri, 14 Aug 1998 09:39:49 -0400
From: "Algranati, Nancy {~Nutley}"
Subject: RE: PharmPK Acetaminophen toxicity in children
To: "'PharmPK.-a-.pharm.cpb.uokhsc.edu'"
Mime-Version: 1.0
The recommended maximum dose of acetaminophen in children is 90 mg/kg.
A single dose of 150 mg/kg or greater necessitates treatment for APAP
toxicity including activated charcoal and n-acetylcysteine therapy to
prevent hepatotoxicity. LFT's (AST and ALT) begin to rise within 24
hours post ingestion and peak approximately 48-72 hours post ingestion.
Severe toxicity is usually defined as AST or ALT >1000 IU/L. Hepatic
toxicity is rare at recommended doses, however, some more information
would be helpful to answer your inquiry.
1. How old is the infant?
2. How much does the infant weigh?
3. Does the infant have any underlying conditions, and what was the
condition that you were treating with the APAP?
4. Did the infant receive a single dose or multiple doses of APAP? How
frequently were the doses administered?
5. Which APAP preparation was administered? (Sometimes the correct
volume, but the wrong formulation is administered)
It would be advisable to contact your local poison control center if
there is an immediate issue.
After a quick literature search, here are some relevant references:
* Eur J Clin Pharmacol 1984;27(1):57-59
Acetaminophen accumulation in pediatric patients after repeated
therapeutic doses.
Nahata MC, Powell DA, Durrell DE, Miller MA
Acetaminophen serum concentrations were studied in 21 infants and
children with fever. The maximum serum concentrations ranged from 9.96
to 19.6
micrograms/ml after a single dose of 12-14 mg/kg and 13.9 to 40.1
micrograms/ml after a single dose of 22-27 mg/kg. Ten patients were
restudied at steady-state
after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total
area under the acetaminophen serum concentration-time curve normalized
for dose averaged
0.181 (ml/min/kg)-1 after the first dose and 0.202 (ml/min/kg)-1 at
steady-state (p less than 0.05). Five patients showed a 13 to 44%
increase in the AUC; one had
a 10% decrease in the AUC; and four had less than 6% change in the AUC.
There was no evidence of hepatotoxicity. These data suggest that
acetaminophen may
accumulate after repeated therapeutic doses in children with fever.
* Am J Dis Child 1983 Apr;137(4):386-387
Acetaminophen poisoning in infancy.
Greene JW, Craft L, Ghishan F
Acetaminophen is widely used in children of all ages, and overdosage
from this medication is common. Although severe hepatotoxicity from
over-dosage occurs in
adults, acetaminophen seems to have a wide margin of safety in younger
children. This has been ascribed to altered pharmacokinetics in this age
group. We report
two cases in which severe acetaminophen-induced hepatoxocity occurred in
two infants. Neither infant reportedly received potentially toxic
dosages, by history, but
toxic drug levels were present in both.
* J Pediatr 1998 Jan;132(1):22-27
Therapeutic misadventures with acetaminophen: hepatoxicity after
multiple doses in children.
Heubi JE, Barbacci MB, Zimmerman HJ
Division of Pediatric Gastroenterology and Nutrition, Children's
Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
We compiled reports of acetaminophen hepatotoxicity after multiple
overdoses from published cases, cases reported to the Food and Drug
Administration, and
cases from Children's Hospital Medical Center, Cincinnati, Ohio.
Forty-seven children (age range, 5 weeks to 10 years) received 60 to 420
mg/kg/day for 1 to 42
days; 52% had received adult preparations of acetaminophen. The mean
peak serum aspartate aminotransferase level was 10,225 IU/L (n = 45),
and the mean
serum alanine aminotransferase level was 7355 IU/L (n = 31), which were
significantly higher (both p < 0.001) than the mean serum aspartate
aminotransferase level
of 3500 IU/L and alanine aminotransferase level of 3098 IU/L found in
children (n = 12) with non-acetaminophen-associated hepatic failure.
Serum acetaminophen
levels for which an estimate of time from last dose could be calculated
were available for 30 patients, of which 22 levels were greater than the
toxic range described
for acute ingestion. Twenty-four of 43 patients (55%) died, with an
additional three surviving after orthotopic liver transplantation.
Parents should be advised about
the potential hepatotoxicity of acetaminophen when given to ill children
in doses exceeding weight-based recommendations.
Best regards,
Nancy Algranati, Pharm.D.
Post-Doctoral Fellow
Hoffmann-La Roche/ Rutgers University
---
Date: Fri, 14 Aug 1998 11:15:01 -0500
From: "Dr. Pippa Simpson"
Organization: UAMS/PEDS/CARE
MIME-Version: 1.0
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Acetomenophen toxicity in children
I know that the american pediatric society have examined this. Dr. Gail
Mccarver
at the childrens hospital of Detroit has been working on this.
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)