Tolerability and efficacy of two synergistic ratios of oral morphine and oxycodone combinations versus morphine in patients with chronic noncancer pain


  • Felix A. de la Iglesia, MD
  • Gary W. Pace, PhD
  • Gary L. W. G. Robinson, PhD
  • Nuo-Yu Huang, MD, PhD
  • Warren Stern, PhD
  • Patricia Richards, MD, PhD



morphine, oxycodone, analgesia, morphine equivalent dose, adverse events, combination


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 of fixed ratio of morphine (M) and oxycodone (O) 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:O2 in study A; M1:O2 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:O = 3:2) or 46.8 percent (study B, M:O = 1:2) more MED were needed for M 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 or1:2 fixed ratio combination of morphine and oxycodone (MOX) produced analgesic synergy and a tolerability profile improvement in patients with chronic noncancer pain.

Author Biographies

Felix A. de la Iglesia, MD

Michigan Technology and Research Institute, Ann Arbor, Michigan.

Gary W. Pace, PhD

QRxPharma Inc., Bedminster, New Jersey.

Gary L. W. G. Robinson, PhD

PhaseDesign Research, Framingham, Massachusetts.

Nuo-Yu Huang, MD, PhD

QRxPharma Inc., Bedminster, New Jersey.

Warren Stern, PhD

QRxPharma Inc., Bedminster, New Jersey.

Patricia Richards, MD, PhD

QRxPharma Inc., Bedminster, New Jersey.


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How to Cite

de la Iglesia, MD, F. A., G. W. Pace, PhD, G. L. W. G. Robinson, PhD, N.-Y. Huang, MD, PhD, W. Stern, PhD, and P. Richards, MD, PhD. “Tolerability and Efficacy of Two Synergistic Ratios of Oral Morphine and Oxycodone Combinations Versus Morphine in Patients With Chronic Noncancer Pain”. Journal of Opioid Management, vol. 8, no. 2, Mar. 2012, pp. 89-98, doi:10.5055/jom.2012.0101.