Oxycodone combinations for pain relief

Abstract

No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment.

Figure 1

Three-dimensional representation of the isobologram generated for the antinociceptive interaction between oxycodone [O] (mg/kg) and morphine [M] (mg/kg). Antinociception was assessed for each drug alone (ED₅₀ doses = the [O] and [M] axis intercepts of the line of additivity) and for three fixed-ratio combinations of oxycodone + morphine (75%:25%, 50%:50% and 25%:75%). The combination ED₅₀ doses (filled circles) were between the origin and the line of additivity (projected onto the horizontal plane in this representation), which is indicative of a synergistic interaction (data obtained from 46).

Figure 2

Increased side effects with gabapentin/oxycodone versus gabapentin monotherapy in 338 patients with painful diabetic neuropathy (121). GI, gastrointestinal; CNS, central nervous system.