Acetaminophen

Serum or plasma

2 mL

0.6 mL

Red-top tube or green-top (heparin) tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant.

Monitor therapeutic drug levels; evaluate for acetaminophen toxicity. Acetaminophen is as effective as aspirin when used for analgesia and antipyresis. It is used to treat headache, mild-to-moderate myalgia, arthralgia, chronic pain of cancer, postpartum pain, postoperative pain, and fever. The ceiling analgesic effect is obtained with a dose of 1 g.

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 six years 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.

Enzymatic

Therapeutic: 10−30 μg/mL

Acetaminophen is an analgesic and antipyretic with little anti-inflammatory properties. It is used for headache, fever, and relief of pain in patients who cannot tolerate aspirin or those with bleeding disorders or peptic ulcers. Acetaminophen is the analgesic/antipyretic of choice in children 13 years or younger due to the association of aspirin with the possible development of Reye syndrome.

Acetaminophen is rapidly absorbed from the GI tract. Peak plasma concentrations are reached in 30 to 60 minutes. Steady-state concentrations are reached in 10 to 20 hours; however, prolonged (more than 10 days adults; more than five 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 six hours postingestion, then a second level three to four hours later. At normal levels, half-life is one to three hours. Half-lives exceeding four hours are consistent with hepatic necrosis. The Rumack nomogram is available for estimating toxicity from serum level at six hours or later after ingestion.¹ See nomogram.

Hepatic toxicity may appear three to five 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 four 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