Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery

Background: The recommended dose for intravenous (IV) paracetamol injection in adults is I g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose. Methods: A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol I g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration. Results: Two hundred and ninety seven patients (132 = IV paracetamol 2 g; 132 = IV paracetamol I g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6 It (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol I g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2 g were significantly superior to IV paracetamol I g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol I g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests. Conclusion: The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of I g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety. (c) 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.