Intravenous Acetaminophen (Paracetamol): Comparable Analgesic Efficacy, but Better Local Safety than Its Prodrug, Propacetamol, for Postoperative Pain After Third Molar Surgery

Abstract

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.

Safety of Rapid Intravenous Infusion of Acetaminophen

“…Based on the full prescribing information for intravenous acetaminophen (available at http://ofi rmev.com/ include/pdf/OFIRMEVPrescribingInformation.pdf ), the contents of the vial should be administered over 15 minutes. Th is stipulation was based on experience with the prodrug, propacetamol, which caused pain when infused in upwards of 49% of patients (1)(2)(3). Propacetamol, supplied as a powder that needed to be reconstituted for delivery, had a pH of 3.5 to 4 and an osmolarity of 410 mOsmol/L.…”

OFIRMEV: An Old Drug Becomes New Again

“…19 IV acetaminophen has been shown to achieve higher maximum concentrations and earlier time to maximum concentration compared to bioequivalent oral doses with less intrasubject variability. 15,16,[20][21][22] Mean maximum concentration after a standard 15-minute infusion of 1 g acetaminophen is approximately 70% higher than the mean maximum concentration observed at equivalent oral doses. 22 Peak CSF plasma concentrations of IV acetaminophen are 60% higher than with oral administration.…”

“…Nonopioid analgesics are most often given via the oral route; however, many surgical patients are restricted from oral intake or unable to take oral medications because of sedation or postoperative nausea and vomiting. 10,15,16 The oral route may also be less efficacious because intraoperative opioids, inhaled anesthetics, and surgical stress can delay gastric emptying, thereby reducing gastrointestinal absorption of orally administered drugs. 17,18 Intravenous administration of acetaminophen would be an ideal route in the immediate postoperative period, especially in situations where a patient is unable to take medications by mouth or when a faster onset of analgesia is desired.…”

“…6,7 Compared with other analgesics in the treatment of moderate to severe postoperative pain, IV acetaminophen 1 g has a comparable efficacy to ketorolac 30 mg after total hip or knee replacement, diclofenac 75 mg after orthognathic surgery or orthopedic surgery, metamizol 2.5 g after aortic aneurysm repair, and morphine 10 mg after surgical removal of impacted third molar. 14,16,26 In patients who had undergone surgical third-molar extraction complaining of moderate to severe postoperative pain, the use of a 1 g dose of IV acetaminophen was compared with that of a 2 g dose of IV acetaminophen and with placebo. 15,16 In this study, both active treatment groups provided more effective and longer duration of analgesia and better scores on patients' global evaluation (ie, good-excellent) compared to placebo.…”

Translational research in central nervous system drug discovery

“…41 Volunteers are recruited from those individuals scheduled for such a procedure for therapeutic reasons. This model allows intervention at a precisely timed interval with respect to the lesion, typically after induction, but the model is also amenable to evaluation of prophylactic treatments.…”