Tolerability and efficacy of two synergistic ratios of oral morphine and
oxycodone combinations versus morphine in patients with chronic noncancer pain.
Author(s): de la Iglesia FA, Pace GW, Robinson GL, Huang NY, Stern W, Richards P.
Affiliation(s): Michigan Technology and Research Institute, Ann Arbor, Michigan, USA.
Publication date & source: 2012, J Opioid Manag. , 8(2):89-98
OBJECTIVES: Analgesic synergy and improved tolerability have been reported for
flexible dose morphine and oxycodone combinations. This report describes two
studies with similar double-blind, randomized, 7-day crossover designs (up to 7
days per arm) conducted to 1) explore the analgesic and safety benefit offixed
ratio of morphine (M) and oxycodone (0) combinations (MOX) and 2) define the
optimal ratio for morphine and oxycodone combination.
SETTING: Clinical study centers in Australia.
PATIENTS: Patients with chronic noncancer pain.
INTERVENTION: Eligible patients were randomly assigned to receive flexible doses
of either M or fixed ratio of MOX (M3:02 in study A; M1:02 in study B). The
starting doses of M or MOX were the morphine equivalent doses (MEDs) converted
from the analgesics received before entering double-blind treatment. At each
crossover period, the doses were titrated to achieve analgesia at steady state,
which was defined as when the same total daily dose (+/-10 percent) had been
given consecutively for 3 days. Main outcome measure: The primary endpoint was
the study medication dose (MED), which produced adequate pain control at steady
state.
RESULTS: Analgesic synergy in MOX was observed in both studies. On an MED basis,
61.6 percent (study A, M:0 = 3:2) or 46.8 percent (study B, M:0 = 1:2) more MED
were needed forM monotherapy to achieve steady-state pain control when compared
with MOX. Patient tolerability profiles were also generally better in the MOX
groups.
CONCLUSION: A 3:2 or 1:2 fixed ratio combination of morphine and oxycodone (MOX)
produced analgesic synergy and a tolerability profile improvement in patients
with chronic noncancer pain.
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