A study of the analgesic efficacy and safety of use of paracetomol formulations after third molar surgery

Abstract

Objective To compare the analgesic efficacy and safety of a sustained release (SR) paracetamol formulation (Panadol Extend) with a standard immediate release (IR) formulation (Panadol) after third molar surgery. Design A multi-centre, double-blind, randomised clinical trial. Methods Patients received either a single oral dose of SR paracetamol or IR paracetamol for pain after the removal of at least one impacted third molar requiring bone removal under general anaesthesia. Post-operative pain and pain relief assessments were undertaken at time intervals up to 8 hours. Global assessments of effectiveness were made at 4 and 8 hours. Any adverse events were also recorded. Results Of 627 randomised patients, 314 were treated with SR paracetamol and 313 with IR paracetamol. In the per protocol population at 4 hours, 35.1% of the 252 patients on SR paracetamol rated the study medication as very good or excellent compared with 27.7% of the 258 patients on IR paracetamol. There were few statistically significant differences among the secondary parameters but where they did occur they favoured SR paracetamol. Trends in favour of SR paracetamol were observed among the secondary parameters and these tended to emerge at the later time points. For example, while there was no statistically significant difference in time to re-medication between the treatment groups, the estimated time to re-medication was longer for patients treated with SR paracetamol (4 hr 5 min) compared with IR paracetamol (3 hr 10 min). The high rate of re-medication observed is consistent with that reported for IR paracetamol using the post-operative dental pain model. No difference was observed between the SR paracetamol and IR paracetamol treatment groups in distribution, incidence or severity of adverse events. Conclusions SR paracetamol and IR paracetamol are clinically and statistically equivalent. While SR paracetamol and IR paracetamol were similar in terms of both onset of analgesia and peak analgesic effect, SR paracetamol had a longer duration of activity than IR paracetamol. The safety profiles of SR paracetamol and IR paracetamol were found to be very similar.