TYLENOL® (acetaminophen) Use in Certain Disease States and Conditions
Note: This information is also available in referenced form in the TYLENOL® product monograph. (View PDF)
- Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- Use in Chronic Liver Disease
- Use in Renal Disease
- Use in Older Patients
"Acetaminophen can be used safely in patients with liver disease and is a preferred analgesic/antipyretic because of the absence of the platelet impairment, gastrointestinal toxicity, and nephrotoxicity associated with nonsteroidal anti-inflammatory drugs."
-Benson GD, Koff RS, Tolman KG. The Therapeutic Use of Acetaminophen in Patients with Liver Disease. American Journal of Therapeutics. 2005;12:133-141.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
In therapeutic doses, acetaminophen does not shorten the lifespan of red blood cells and does not produce any clinically perceptible destruction of circulating red blood cells.
Acetaminophen Use in Chronic Liver Disease
Acetaminophen can be used in patients with liver disease and has been studied in both one-time single (1500 mg) and multiple doses (4000 mg/d) in adult patients with chronic stable liver disease. Benson conducted a double-blind, two-period, crossover study that evaluated the use of 4000 mg/d of acetaminophen for 13 days in patients with stable chronic liver disease. There were no abnormalities indicative of an adverse reaction to acetaminophen. Forrest and associates compared acetaminophen metabolism following a single 1500-mg dose in normal subjects, patients with mild liver disease, and patients with severe liver disease. There were no significant differences in overall 24-hour urinary excretion of acetaminophen and glucuronide, sulfate, cysteine, and mercapturic acid conjugates of acetaminophen. Following a single (10 mg/kg) dose of acetaminophen, the pharmacokinetic profiles in pediatric patients with mild, moderate, or severe liver disease were not significantly different. Although the plasma half-life of acetaminophen was prolonged in patients with severe liver disease, there were no significant differences in the 24-hour (adult) and 36-hour (children) urinary excretion of acetaminophen or its conjugates (eg, glucuronide, sulfate, cysteine, mercapturic acid).
Acetaminophen Use in Renal Disease
Based on available clinical data, acetaminophen can be used in patients with chronic renal disease without dosage adjustment. In a single-dose study, Prescott and colleagues compared the disposition and metabolite kinetics of 1000 mg of acetaminophen in patients with renal disease and in healthy volunteers. The fractional urinary recovery of acetaminophen and its conjugates (eg, glucuronide, sulfate, cysteine, mercapturate) was similar in healthy volunteers and in patients with moderate renal failure. In a 10-day, multi-dose study, Martin and associates evaluated the disposition of acetaminophen 3000 mg daily in healthy volunteers compared with patients with chronic renal failure. A slight increase in predose trough acetaminophen levels was noted in patients with renal failure (3.1 µg/mL) compared with controls (1.1 µg/mL), but there was no evidence of accumulation of the glutathione-derived metabolites of acetaminophen (eg, cysteine, mercapturate). Although mean daily predose plasma concentrations of sulfate and glucuronide conjugates were higher in patients with chronic renal disease, these conjugates disappeared rapidly when acetaminophen was discontinued. There is no significant risk of acetaminophen toxicity in patients with moderate to severe renal failure.
A National Kidney Foundation position paper notes that physicians preferentially recommend acetaminophen to patients with renal failure because of the bleeding complications associated with aspirin in these individuals. In this position paper, acetaminophen was recommended as the non-narcotic analgesic of choice for episodic use in patients with underlying renal disease.
Acetaminophen Use in Older Patients
No adjustment in labeled dosage is necessary for older patients who require acetaminophen therapy. Those who require therapy for longer than 10 days should consult their physician for condition monitoring; however, no reduction in recommended dosage is necessary. The American Geriatrics Society Clinical Practice Guidelines for the Management of Chronic Pain in Older Persons recommend acetaminophen as the drug of choice for relieving mild to moderate musculoskeletal pain, with the maximum dosage not to exceed 4000 mg daily.