When evaluating for possible toxicity, a 4- to 6-hour postingestion sample should be drawn. Collect a second sample 3-4 hours later.

Acetaminophen is the preferred alternative to aspirin for patients who cannot tolerate the latter, those with a coagulation disorder, or individuals with a history of peptic ulcer or reflux esophagitis. In children requiring only analgesia or antipyresis, acetaminophen may be preferred to aspirin because it is less toxic if an accidental overdose occurs. (Interestingly, acetaminophen overdosage in children younger than 6 is rarely, if ever, associated with hepatotoxicity, but such protection is lost by adolescence.) Further, no epidemiological association has been demonstrated between acetaminophen and Reye syndrome in children or adolescents with influenza A or B or varicella (chickenpox).

Acetaminophen is unsatisfactory for conditions requiring potent anti-inflammatory activity (rheumatic disease, juvenile arthritis, dysmenorrhea, sunburn). Unlike aspirin, acetaminophen does not antagonize the effects of uricosuric agents and may be used in patients with gouty arthritis who are taking a uricosuric.

Acetaminophen is rapidly absorbed from the GI tract. Peak plasma concentrations are reached in 30-60 minutes. Steady-state concentrations are reached in 10-20 hours. However, prolonged (more than 10 days adults; more than 5 days children) treatment is to be avoided. Acetaminophen is metabolized to several conjugated forms, glucuronide (45% to 55%), sulfate (20% to 30%), and cysteine and mercaptopurine (20%). Acetanilide and phenacetin owe much of their analgesic effect to their metabolite, acetaminophen.

The best indicator of acetaminophen toxicity is to measure the drug half-life by analyzing a blood level taken 6 hours postingestion, then a second level 3-4 hours later. At normal levels, half-life is 1-3 hours. Half-lives exceeding 4 hours are consistent with hepatic necrosis. The Rumack nomogram is available for estimating toxicity from serum level at 6 hours or later after ingestion.¹ See nomogram.

Hepatic toxicity may appear 3-5 days after ingestion of a toxic dose. Toxic levels require monitoring liver function with AST (SGOT), ALT (SGPT), and bilirubin with study also of glucose, creatinine, prothrombin time, and electrolytes. Serum levels drawn before 4 hours may not represent peak levels. The hepatotoxicity of acetaminophen is related to the formation of one or more highly reactive metabolites in the liver. Impaired hepatic metabolism may be found in the elderly. Orally administered N-acetylcysteine (Mucomyst®) has been shown to provide rather dramatic protection against acetaminophen hepatotoxicity. Early treatment is especially recommended in pregnant subjects.²