Randomized Clinical Trial of Hydrocodone/Acetaminophen Versus Codeine/Acetaminophen in the Treatment of Acute Extremity Pain After Emergency Department Discharge

Abstract

ObjectivesThe objective was to test the hypothesis that hydrocodone/acetaminophen (Vicodin [5/500]) provides more efficacious analgesia than codeine/acetaminophen (Tylenol #3 [30/300]) in patients discharged from the emergency department (ED). Both are currently Drug Enforcement Administration (DEA) Schedule III narcotics.MethodsThis was a prospective, randomized, double‐blind, clinical trial of patients with acute extremity pain who were discharged home from the ED, comparing a 3‐day supply of oral hydrocodone/acetaminophen (5 mg/500 mg) to oral codeine/acetaminophen (30 mg/300 mg). Pain was measured on a valid and reproducible verbal numeric rating scale (NRS) ranging from 0 to 10, and patients were contacted by telephone approximately 24 hours after being discharged. The primary outcome was the between‐group difference in improvement in pain at 2 hours following the most recent ingestion of the study drug, relative to the time of phone contact after ED discharge. Secondary outcomes compared side‐effect profiles and patient satisfaction.ResultsThe median time from ED discharge to follow‐up was 26 hours (interquartile range [IQR] = 24 to 39 hours). The mean NRS pain score before the most recent dose of pain medication after ED discharge was 7.6 NRS units for both groups. The mean decrease in pain scores 2 hours after pain medications were taken were 3.9 NRS units in the hydrocodone/acetaminophen group versus 3.5 NRS units in the codeine/acetaminophen group, for a difference of 0.4 NRS units (95% confidence interval [CI] = –0.3 to 1.2 NRS units). No differences were found in side effects or patient satisfaction.ConclusionsBoth medications decreased NRS pain scores by approximately 50%. However, the oral hydrocodone/acetaminophen failed to provide clinically or statistically superior pain relief compared to oral codeine/acetaminophen when prescribed to patients discharged from the ED with acute extremity pain. Similarly, there were no clinically or statistically important differences in side‐effect profiles or patient satisfaction. If the DEA reclassifies hydrocodone as a Schedule II narcotic, as recently recommended by its advisory board, our data suggest that the codeine/acetaminophen may be a clinically reasonable Schedule III substitute for hydrocodone/acetaminophen at ED discharge. These findings should be regarded as tentative and require independent validation in similar and other acute pain models.

Comparative Analgesic Efficacy of Oxycodone/Acetaminophen Versus Hydrocodone/Acetaminophen for Short‐term Pain Management in Adults Following ED Discharge

“…was 12% 8 and 10% with hydrocodone/acetaminophen (5 mg/325 mg). 7 In our study, dizziness was also significantly more frequent in patients who received oxycodone/acetaminophen (5 mg/325 mg) than in those who received hydrocodone/acetaminophen (5 mg/325 mg; 17.0% vs. 7.2%; Table 3).…”

Pharmacogenetics for Safe Codeine Use in Sickle Cell Disease

“…35 Recent data show comparable efficacy between codeine/acetaminophen (Schedule III) and oxycodone/acetaminophen (Schedule II) as well as codeine/ acetaminophen and hydrocodone/ acetaminophen (Schedule II) for the treatment of acute pain. 36,37 The rescheduling of hydrocodonecontaining analgesics and codeine's ability to adequately provide analgesia in comparison with Schedule II analgesics has reinforced our preference to retain codeine on the hospital formulary and to initiate measures that ensure its safe and effective use.We chose a precision medicine approach to codeine prescribing by implementing a pharmacogeneticsbased prescribing strategy to guide the rational use of codeine across the institution. Such an approach could optimize the use of codeine in SCD and other chronic, recurrent pain disorders by reducing the incidence of excessive toxicity and poor analgesic effect.…”

“…35 Recent data show comparable efficacy between codeine/acetaminophen (Schedule III) and oxycodone/acetaminophen (Schedule II) as well as codeine/ acetaminophen and hydrocodone/ acetaminophen (Schedule II) for the treatment of acute pain. 36,37 The rescheduling of hydrocodonecontaining analgesics and codeine's ability to adequately provide analgesia in comparison with Schedule II analgesics has reinforced our preference to retain codeine on the hospital formulary and to initiate measures that ensure its safe and effective use.…”

A Challenging Crossroad for Emergency Medicine: The Epidemics of Pain and Pain Medication Deaths

“…Mazer-Amirshahi et al 3 describe eye-opening trends in ED analgesic prescribing over a period of 10 years, Chang et al 4 examine the efficacy and adverse effects of two opioid pain relievers commonly prescribed at ED discharge for the treatment of extremity pain, and Kilaru et al 5 evaluate a narrative format to help emergency physicians (EPs) increase content recall of new American College of Emergency Physicians (ACEP) opioid prescribing guidelines. Each of these studies contributes some insight into this complex problem.…”

“…With that caveat, Chang and colleagues in the second study published this month examined the use of two combination opioid pain relievers (codeine/acetaminophen vs. hydrocodone/acetaminophen) following ED discharge for the treatment of extremity pain. 4 They were particularly interested in evaluating the efficacy and adverse effect profile of codeine/acetaminophen (Tylenol#3) because of the impending planned controlled substances scheduling changes of hydrocodone/acetaminophen to Schedule II. Thus, codeine/acetaminophen will be the only opioid pain reliever to remain as an option to Schedule III prescribers (some midlevel providers are restricted to Schedule III controlled substance prescribing in some states).…”