Comparison of the Efficacy and Safety of Dual-Opioid Treatment With Morphine Plus Oxycodone Versus Oxycodone/Acetaminophen for Moderate to Severe Acute Pain After Total Knee Arthroplasty

• Published in: Clinical therapeutics 2013-04, Vol.35 (4), p.498-511
• Main Authors: Richards, Patricia, MD, PhD, Gimbel, Joseph S., MD, Minkowitz, Harold S., MD, Kelen, Robin, MS, Stern, Warren, PhD
• Format: Article
• Language: English
• Subjects: Acetaminophen - administration & dosage; Acetaminophen - therapeutic use; Aged; Algorithms; Analgesics; Biological and medical sciences; Drug therapy; Drug Therapy, Combination; dual opioid; Female; gastrointestinal adverse effects; Humans; Internal Medicine; Joint surgery; Male; Medical Education; Medical sciences; Middle Aged; morphine; Morphine - administration & dosage; Morphine - therapeutic use; morphine/oxycodone; Narcotics; nausea; oxycodone; Oxycodone - administration & dosage; Oxycodone - therapeutic use; oxycodone/acetaminophen; Pain management; Pain, Postoperative - drug therapy; Pharmacology. Drug treatments; postoperative pain; Severity of Illness Index; total knee arthroplasty; vomiting
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2013.03.002

Abstract Background In acute pain models, coadministration of low doses of morphine and oxycodone markedly enhanced analgesia relative to either opioid given alone. Enhanced analgesia with coadministration of morphine and oxycodone has also been reported in acute and chronic moderate to severe pain conditions during double-blind studies. Objective The goal of this study was to compare the efficacy and tolerability of a flexible dose regimen of the morphine/oxycodone combination versus oxycodone/acetaminophen and fixed low-dose morphine/oxycodone. Methods This was a 5-center, randomized, open-label study of hospitalized patients (n = 44) with acute moderate to severe postoperative pain after total knee arthroplasty. Inpatients were randomized to a flexible dose regimen of morphine/oxycodone (3 mg/2 mg to 24 mg/16 mg), fixed low-dose morphine/oxycodone regimen (3 mg/2 mg), or oxycodone/acetaminophen (5 mg/325 mg). Treatment was initiated following surgery after intravenous (IV) morphine patient-controlled analgesia. An algorithm was evaluated for converting the patient-controlled analgesia morphine dose to an initial oral dose of morphine/oxycodone. The primary efficacy variable was the time-weighted sum of pain intensity difference from 0 to 48 hours. Results The median values for the sum of the pain intensity difference from 0 to 48 hours for the morphine/oxycodone flexible dose and oxycodone/acetaminophen were similar and approximately twice that of fixed morphine/oxycodone 3 mg/2 mg (148.0, 139.5, and 71.3, respectively). Moderate to severe gastrointestinal adverse events occurred in 50% of patients in the oxycodone/acetaminophen group compared with 15% of the equianalgesic morphine/oxycodone group. On several items of the Brief Pain Inventory (general activity, walking ability, and sleep), the morphine/oxycodone flexible dose produced greater benefit than oxycodone/acetaminophen. Conclusions Flexible dose morphine/oxycodone was superior to low-dose morphine/oxycodone and comparable to oxycodone/acetaminophen. Flexible dose morphine/oxycodone-treated patients had a lower rate of moderate to severe nausea or vomiting than equianalgesic oxycodone/acetaminophen-treated patients. Thus, morphine/oxycodone offers an attractive alternative to oxycodone/acetaminophen for the management of moderate to severe postoperative pain. ClinicalTrials.gov : identifier: NCT00818493.