Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial

ABSTRACT

Objectives

Opioid/acetaminophen combinations may be overly prescribed in many post-surgical situations where a non-steroidal anti-inflammatory drug with equal or greater efficacy, fewer central nervous system side effects, and no risk for opioid abuse could be substituted. We compared a single, non-prescription dose of naproxen sodium 440 mg (NapS) against hydrocodone plus acetaminophen 10/650 mg (HYD+APAP) in post-impaction surgery pain.

Methods

Single-center, randomized, double-blind, placebo-controlled study in moderate-severe pain after surgical removal of impacted third molars (ClinicalTrials.gov: NCT04307940). Patients (n = 212) received NapS, HYD+APAP, or placebo and were assessed over 12 hours. Primary endpoint: summed pain intensity difference from 0 to 12 hours (SPID_0-12). Secondary endpoints: pain intensity, pain relief, time to rescue medication, duration of pain at least half gone. Others: onset of pain relief, global assessment of treatment, adverse events.

Results

All 221 randomized patients formed the safety population and were included in the intention-to-treat sensitivity analysis. Nine patients discontinued treatment or had protocol violations, and 212 patients were included in the per-protocol, primary efficacy population. Both active treatments were significantly more effective than placebo. NapS was significantly more effective than HYD+APAP regarding SPID_0-12 (p = 0.01; primary endpoint), total pain relief (0–6 and 0–12 hours; p < 0.05), time to rescue medication (p < 0.001), and duration of pain at least half gone (p < 0.001). HYD+APAP was not statistically superior to NapS for any endpoint. More adverse events were reported with HYD+APAP (n = 63) than NapS (n = 2) and placebo (n = 20), including nausea, vomiting, and dizziness.

Conclusion

In moderate-to-severe postsurgical dental pain, a single dose of NapS was at least as effective as HYD+APAP in the early hours, significantly more effective at reducing pain intensity and providing greater pain relief over 12 hours, and was better tolerated. When not contraindicated, NapS should be considered a preferred alternative to opioid combinations for acute pain. (ClinicalTrials.gov, Identifier: NCT04307940; https://clinicaltrials.gov/ct2/show/NCT04307940)

KEYWORDS:

• Acetaminophen
• dental pain
• hydrocodone
• naproxen sodium
• non-steroidal anti-inflammatory drugs
• opioids
• pain relief

ORCID IDs

Stephen A. Cooper: ORCID ID 0000-0002-3073-1096

Paul J Desjardins: ORCID ID 0000-0002-5870-6546

Todd Bertoch: ORCID ID 0000-0001-9896-5238

Alberto Paredes-Diaz: ORCID ID 0000-0003-0427-7552

Emanuel Troullos: ORCID 0000-0001-7512-4276

Azita Tajaddini: ORCID ID 0000-0003-2018-6335

Robert Centofanti: ORCID ID 0000-0003-2240-5714

Robert An: ORCID ID 0000-0001-5583-8044

Donna Morella: ORCID ID 0000-0001-5987-1677

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Acknowledgments

The manuscript was drafted and edited by a medical writer (Deborah Nock, Medical WriteAway, Norwich, UK), with full contribution, review, and approval by all authors.

Declaration of funding

This study was sponsored and funded by Bayer HealthCare, LLC, Consumer Health, Whippany, NJ, USA, including the services of the medical writer. Bayer was involved in protocol development, monitoring, overseeing the CRO that conducted the study and overseeing the CRO responsible for data management and biostatistics. Peer reviewers had no conflicts of interest on this manuscript.

Disclosure of financial/other conflicts of interest

S.A.C. and P.J.D are both consultants for Bayer HealthCare, LLC, and members of the JBR Scientific Advisory Board. T.B. is employed by JBR Clinical Research. A.P-D., A.T., R.C., R.A., and D.M. are all employees of Bayer HealthCare, LLC. E.T. is performing contractor work for Bayer HealthCare, LLC.

Author contributions

S.A.C.: Conceptualization, Methodology, Investigation, Roles/Writing – review & editing; P.J.D: Conceptualization, Methodology, Visualization, Roles/Writing – Original Draft, Review & Editing; T.B.: Formal Analysis, Project Administration, Methodology, Investigation, Supervision, Visualization, Roles/Writing – review & editing; A.P.-D.: Conceptualization, Data Curation, Formal Analysis, Methodology, Supervision, Roles/Writing – review & editing; E.T.: Conceptualization, Methodology, Roles/Writing – Original Draft, Review & Editing; A.T.: Formal Analysis, Project Administration, Supervision, Validation, Visualization, Roles/Writing – Original Draft, Review & Editing; R.C.: Funding Acquisition, Project Administration, Methodology, Supervision; R.A.: Conceptualization, Data Curation, Formal Analysis, Methodology, Resources, Supervision, Validation; D.M.: Formal Analysis, Project Administration, Roles/Writing – review & editing.

Supplementary data

Supplemental data for this article can be accessed here