Acetaminophen
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Overdose and toxicity
[edit | edit source]For a single acute ingestion at a known time, the Rumack-Matthew nomogram guides whether to treat: a serum acetaminophen concentration is drawn no earlier than 4 hours after ingestion and plotted against time.[2] In the United States the treatment line begins at 150 micrograms/mL at 4 hours (set 25% below Rumack and Matthew's original 200 micrograms/mL line, the FDA-adopted treatment threshold); a level on or above the line indicates N-acetylcysteine, a level below it does not.[3] The nomogram does NOT apply to chronic or repeated (staggered) ingestion, an unknown ingestion time, levels drawn before 4 hours, or modified/extended-release products; in those situations N-acetylcysteine is given empirically with serial transaminase and acetaminophen monitoring.
Two established N-acetylcysteine regimens are used. The intravenous 21-hour (Prescott) regimen gives 150 mg/kg as a loading dose, then 50 mg/kg over the next 4 hours, then 100 mg/kg over the following 16 hours.[4] The oral 72-hour regimen gives a 140 mg/kg loading dose, then 70 mg/kg every 4 hours for 17 doses.[5] Treatment is most effective when started within 8 hours of ingestion, but is still given later, and in established liver injury or acute liver failure, where it improves outcomes. Massive or late-presenting overdose may require extended or increased dosing. This is reference information, not a treatment protocol; overdose is a medical emergency managed by clinicians and poison control.
Combination products and the 325 mg limit
[edit | edit source]Because acetaminophen is present in many products at once -- prescription opioid combinations (e.g. hydrocodone/acetaminophen, oxycodone/acetaminophen) and over-the- counter cold, flu, and sleep products -- people can exceed the maximum daily dose without realizing it by stacking several acetaminophen-containing products, a leading route to unintentional hepatotoxicity. In January 2011 the FDA acted on this risk for PRESCRIPTION acetaminophen products: it asked manufacturers to limit acetaminophen to 325 mg per dosage unit in prescription combination products (a change manufacturers completed by 2014), and it required a boxed warning on all prescription products containing acetaminophen highlighting the potential for severe liver injury.[6] Over-the-counter acetaminophen products instead carry a Drug Facts "Liver warning," not a boxed warning. Checking every product label for acetaminophen (sometimes abbreviated APAP) and summing the total is the practical safeguard.
References
[edit | edit source]- ↑ 1.0 1.1 1.2 FDA OTC Monograph for acetaminophen-containing products, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021450s015lbl.pdf
- ↑ Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871-876.
- ↑ Wallace CI, Dargan PI, Jones AL. Paracetamol overdose: an evidence based flowchart to guide management. Emerg Med J. 2002;19(3):202-205.
- ↑ Prescott LF, Illingworth RN, Critchley JA, et al. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. Br Med J. 1979;2(6198):1097-1100.
- ↑ Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med. 1988;319(24):1557-1562.
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: Prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. January 13, 2011.