Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: a placebo-controlled, randomized study.

BACKGROUND: For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD)pain scores measured on a visual analogue scale (48.6 ± 23.1 mm versus 55.9 ± 25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1 ± 0.8 versus 2.4 ± 0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity.

An evaluation of a clinical pharmacokinetic service for serum digoxin levels.

The appropriateness of requests by physicians for serum digoxin measurements (SDMs) and the appropriateness of responses by physicians to a reported SDM were evaluated with and without the contribution of a pharmacy-based clinical pharmacokinetic service (CPS). Also, for each patient, the difference between dosage regimens that had been established by means of SDMs and those regimens that would have been estimated by the method of Dobbs et al. was analyzed. This prospective evaluation involved two 3-week phases and included inpatients. During phase I the CPS was intact, while during phase II it was discontinued. There was a significant increase from phase I (23.4%) to phase II (36.4%) in the rate of inappropriate action or inaction with respect to requesting SDMs. There was also a significant increase from 9.7 to 24.6% in the rate of inappropriate dosage adjustments in response to a reported SDM. There was a statistically significant difference between the digoxin dosages estimated by the method of Dobbs et al. and the actual dosage regimen established with SDMs. The disparity between the CPS approach and the Dobb et al. method was such that 23.4% of digoxin dosage regimens determined with the guidance of SDMs did not result in an estimated steady-state level within the therapeutic range when those regimens were applied to the Dobbs et al. method. Thus, the pharmacy-based CPS improved the appropriateness of physician utilization of SDMs. Also, sole use of the Dobbs et al. method as an example of a noninvasive approach to digoxin dosing is not a reasonable alternative in a tertiary care institution.