Opioid Rescue Use During Around-The-Clock Ibuprofen plus Acetaminophen Following Third Molar Extraction

Katherine N. Theken

Theken, Katherine N.1, Hersh, Elliot V.2, Secreto, Stacey A.2, Wang, Steven2, Panchal, Neeraj2, Habib, Rania2, Mitchell, Claire H.3, Farrar, John, T.4, Grosser, Tilo5
1University of Pennsylvania Perelman School of Medicine, Institute for Translational Medicine and Therapeutics and Oral Surgery and Pharmacology
2University of Pennsylvania School of Dental Medicine, Department of Oral & Maxillofacial Surgery/Pharmacology
3University of Pennsylvania School of Dental Medicine, Department of Basic and Translational Sciences
4University of Pennsylvania Perelman School of Medicine, Biostatistics and Epidemiology
5University of Pennsylvania Perelman School of Medicine,Institute for Translational Medicine and Therapeutics


Ibuprofen 400 mg plus acetaminophen 500 mg (IBU/APAP) is recommended as a first-line non-opioid analgesic strategy for pain following the surgical removal of impacted third molars. The aim of this part of the study was to confirm the opioid sparing effect of this regimen.


This is an ongoing study in patients undergoing surgical extraction of partial or full bony impacted third molars. While local anesthesia dissipates, patients are evaluated for pain intensity, employing a numeric rating scale (0=no pain; 10=worst imaginable). When pain intensity reaches ≥4/10, patients are administered rapid-acting solubilized ibuprofen (400 mg) or placebo (3:1) in a randomized, double-blind design. Following the initial 4-hour evaluation period, all patients transitioned to open-label IBU/APAP taken every 4 hours around-the-clock for 48 hours. Patients were provided with eight oxycodone 5 mg tablets for intolerable breakthrough pain.


To date, 44 patients have completed the study (18-35 years, 32 women), and 17 patients required rescue medication within 4h of blinded study medication treatment. After discharge, IBU/APAP provided adequate analgesia in the majority of patients, with only 7 patients (15.9%) using oxycodone during the open-label phase. The median (interquartile range) number of opioid pills taken for those who required them was 3 (2.5, 6.5).


IBU/APAP provided effective analgesia for the treatment of moderate-to-severe pain in dental impaction surgery patients. The need for additional oxycodone was low. Future analysis will investigate the mechanisms underlying the heterogeneity in analgesic response and need for opioid rescue medication.