Acetaminophen Overdose in Pregnancy

Jason M. Wilkes, MD; Larry E. Clark, MD; Jorge L. Herrera, MD


South Med J. 2005;98(11):1118-1122. 

In This Article


In September 1976, the Food and Drug Administration gave an Investigational New Drug License to the Rocky Mountain Poison and Drug Center for the use of oral NAC in the treatment of APAP poisoning.[18] The treatment protocol for oral NAC was a loading dose of 140 mg/kg orally followed by 17 maintenance doses of 70 mg/kg orally every 4 hours. If the patient's history indicated ingestion of 7.5 g or more and an APAP level was not available immediately, the recommendation was to initiate treatment and then discontinue it later if the level was determined to be nontoxic. One hundred thirteen women who were reported to be in various stages of pregnancy were entered into the study protocol from 1976 to 1985. Follow-up, including appropriate laboratory and pregnancy outcome data, was available in 60 cases, 24 of which had APAP levels above the APAP overdose nomogram line. Ten were treated within 10 hours of ingestion, 10 were treated 10 to 16 hours after ingestion, and 4 were treated 16 to 24 hours after ingestion. Of the 10 who were treated within 10 hours of ingestion, 8 delivered normal infants and 2 had elective abortions. Of the 10 patients receiving NAC 10 to 16 hours after ingestion, 5 delivered viable infants, 2 had elective abortions, and 3 had spontaneous abortions. Of 4 women receiving NAC 16 to 24 hours after ingestion, 3 patients had hepatotoxicity and 1 patient died. There was one spontaneous abortion, one stillbirth, one elective abortion, and one delivery. There was a significantly increased probability of fetal death if the mother received the loading dose of NAC late after ingestion (P = 0.002) or if she took an overdose early in pregnancy (P = 0.014). However, it is important to note that the study group was a small number of patients who were neither randomly selected nor part of a case-control study. This study in addition to other case reports supports the early administration of NAC in APAP overdose in pregnancy.[36,37]

When a patient presents with a probable toxic ingestion of APAP, blood should be drawn for measurement of APAP level and treatment started immediately.[1,32] If the level during the initial period of 4 to 16 hours is found to be predictive of no liver injury, NAC may be stopped. If the level is borderline or predictive of injury, treatment should be completed. As with all patients ingesting toxic quantities of APAP, the best outcomes occur in patients who receive NAC within 16 hours of ingestion. Treatment 16 to 24 hours after ingestion and perhaps longer is still indicated, even though it may be less effective.[38]

There may be occasions in which oral NAC may not be feasible because of nausea, vomiting, anorexia, and/or altered mental status. Nasogastric tube administration may be considered for these patients. This still may not be possible for all cases. In the United Kingdom and Canada, NAC has been available as an intravenous preparation.[1] In January 2004, the Food and Drug Administration approved the use of intravenous NAC (Acetadote®) for use within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen. The most frequently reported adverse events attributed to intravenous acetylcysteine administration include rash, urticaria, and pruritus, with frequency between 0.2% and 20.8%, and may be particularly severe in cases with preexisting bronchospasm.[39] Systemic anaphylaxis may also occur in response to intravenous NAC. Circumstances in which intravenous administration of NAC would be advantageous include inability to tolerate oral NAC, coingestion with other noxious product necessitating ongoing gastrointestinal lavage, gastrointestinal bleeding or obstruction, APAP toxicity presenting as encephalopathy, neonatal APAP toxicity from maternal overdose, and medical or surgical conditions precluding oral NAC administration.[40,41,42,43] Data are limited regarding the safety and efficacy of intravenous acetylcysteine in pregnant women. No serious toxicity inherent to pregnancy has been reported in the few cases treated so far, but experience is very limited.


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