Efficacy of Oral vs. Intravenous Acetaminophen

The comparative efficacy of intravenous (IV) to oral (PO-'per os') acetaminophen is understudied and largely unknown. Intravenous acetaminophen has been available since 2010 (http://www.accessdata.fda.gov/drugsatfda\_docs/label/2010/022450lbl.pdf) and has proven superiority over placebo in human clinical trials. It is clearly advantageous in patients who cannot take oral medications. Similarly, oral acetaminophen has proven efficacy in the management of postoperative pain. However, in patients who can receive either formulation the incremental cost of the IV formulation, both to the Health System and patient, is substantial. This incremental cost would be justifiable if there were clear efficacy or safety data to support the preferential use of IV over PO acetaminophen. However, there is no evidence of superior safety and there are only two studies to our knowledge investigating the question of comparative efficacy. Fenlon et al. randomized 130 patients undergoing 3rd molar (i.e., wisdom tooth) removal to IV vs. PO acetaminophen and found that PO acetaminophen was non-inferior to IV acetaminophen. The primary endpoint was postoperative pain score 1h after surgery. No safety concerns were identified in either group. Pettersson et al. randomized cardiac surgery patients to IV or PO acetaminophen, starting immediately postoperatively through the following morning, and found a significant opioid sparing effect of IV acetaminophen but no difference in pain scores or nausea. IV acetaminophen avoids first-pass hepatic metabolism and therefore generates higher serum and cerebrospinal fluid (CSF)/brain levels than does PO acetaminophen (http://ofirmev.com/Pharmacokinetics/). Based on the pharmacokinetic data, one can hypothesize that IV acetaminophen would be superior to PO acetaminophen at time points where serum and/or cerebrospinal fluid drug levels are higher.