Abstract and Introduction
Abstract
Acetaminophen (APAP) is the most common drug overdose in pregnancy. Available data regarding APAP overdose in pregnancy is limited to case reports and a small prospective case series. APAP has been demonstrated to cross the placenta and in toxic doses may harm the fetal and maternal hepatocytes. Fetal hepatocytes metabolize APAP into both active and toxic metabolites. These toxic metabolites may cause fetal hepatic necrosis. N-acetylcysteine (NAC) has also been demonstrated to cross the placenta and may bind toxic metabolites in both the mother and the fetus. Limited data suggest that the majority of morbidity and mortality from APAP overdose can be averted by initiation of NAC within the first 16 hours of ingestion and possibly even later. NAC may be safely administered during pregnancy and should be initiated early after APAP overdosage. The literature was reviewed through the use of OvidMEDLlNE® database, encompassing 1966 to the present. Searches were conducted using the key words acetaminophen, paracetamol, N-acetylcysteine, overdose, and hepatotoxicity. The search was further refined by selecting articles that contained these search words together with the key word pregnancy. Only English language papers were reviewed. Articles were selected on the basis of relevance to the topic. Pertinent citations found in the selected articles were also reviewed.
Introduction
Acetaminophen (APAP), known as paracetamol outside of America, is one of the most widely used over-the-counter medications. and has become the most commonly recommended analgesic during pregnancy.
In 1966, the first clinical evidence of the toxicity of APAP appeared in reports of three apparent suicide attempts, two of which were successful as the result of large overdoses. The United States did not have its first published report of suicidal overdose until 1971. Since that time, APAP has become the most common drug involved in suicidal overdose and fulminant hepatic failure in the United States.
The first reports of APAP overdose in pregnancy resulting in fetal demise were not published until the early 1980s. APAP appears to freely cross the placenta and is in turn metabolized by fetal hepatocytes. Maternal absorption and metabolism of APAP are not affected by pregnancy, and fetal metabolism of APAP occurs. Hepatic necrosis may occur in the fetus after maternal overdose if proper treatment is delayed or not given. Therapy for APAP toxicity consists of N-acetylcysteine (NAC). Based on case reports and limited data, NAC appears to be effective also for the treatment of acetaminophen overdose during pregnancy. NAC crosses the placenta and may provide hepatoprotection to the fetus by binding toxic metabolites within the fetal liver.