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.
Author(s): Richards P(1), Gimbel JS, Minkowitz HS, Kelen R, Stern W.
Affiliation(s): Author information:
(1)QRxPharma, Inc, Bedminster, NJ 07921, USA. patricia.richards@qrxpharma.com
Publication date & source: 2013, Clin Ther. , 35(4):498-511
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.
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