Evaluation of Two Opioid‐Acetaminophen Combinations and Placebo in Postoperative Oral Surgery Pain

Abstract

StudyObjective. To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery.Design. Randomized, double‐blind, single‐dose, placebo‐controlled, parallel‐group study with self‐ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6.Setting. Private, oral surgery practice sites.Patients. Three hundred twenty‐four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow‐up and 32 did not need an analgesic; 232 patients had valid efficacy data.Interventions. Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self‐rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports.Measurements and Main Results. This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone‐acetaminophen combination was significantly superior to the codeine‐acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment.Conclusions. A slight advantage in analgesic efficacy was demonstrated in this single‐dose study for the hydrocodone‐acetaminophen combination. Repeat‐dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.