Long-term efficacy of OROS® hydromorphone combined with pregabalin for chronic non-cancer neuropathic pain.

BACKGROUND AND OBJECTIVES: Treatment for chronic non-cancer neuropathic pain can be complicated by side effects and drug interactions. Combining opioid analgesics and calcium channel modulators may overcome these and improve efficacy. The objective of the present study was to evaluate the efficacy and safety of OROS® hydromorphone combined with pregabalin in patients with chronic non-cancer neuropathic pain. METHODS: This retrospective observational study was conducted on clinical records from patients aged ≥18 years with chronic non-cancer neuropathic [>4 on the Douleur Neuropathique en 4 questions (DN4) scale] pain of ≥6 months duration, with severe intensity [>4 on the Numerical Rating Scale (NRS); range 0-10], who attended all visits and had ≥12 months of follow-up at the Tor Vergata University Polyclinic Hospital, from November 2008 to February 2011. Patients received an oral combination of OROS® hydromorphone and pregabalin. Pain was evaluated at each visit (months 1, 3, 6, 9, and 12) using the NRS and DN4 scale; Patients' Global Impression of Change (PGIC) was administered at months 1, 6, and 12. Dosage and side effects were recorded at each visit. RESULTS: Of 1,292 patients (32 % men, mean ± SD age 67.6 ± 11.9 years), 1,126 attended all visits. Seventeen percent (n = 224) had purely neuropathic pain. Initial mean dosage was 6.06 ± 2.00 mg/day for OROS® hydromorphone, 113.02 ± 21.94 mg/day for pregabalin. Dosages increased up to month 6, and returned to near initial dosages at month 12 (range 4-120 mg/day for OROS® hydromorphone; 75-600 mg/day for pregabalin). NRS pain scores (mean ± standard deviation) were 7.25 ± 1.34 at baseline and 1.85 ± 1.36 at 12 months (p < 0.0001); DN4 scores were 6.19 ± 1.65 at baseline, reduced to 1.84 ± 1.25 at 12 months (p < 0.0001), reductions of 74.4 and 70.2 %, respectively. More than 90 % of patients had a ≥50 % score reduction on both scales after 12 months. The PGIC scale showed that >75 % of patients felt improvement at 1 month, increasing to 91 % and 93 % at 6 and 12 months. The incidence of side effects was similar between elderly (aged >65 years) and younger subjects; there were no cases of addiction. CONCLUSIONS: The OROS® hydromorphone and pregabalin combination was efficacious for chronic non-cancer neuropathic pain and well tolerated, providing significant pain reduction without the risk of addiction and with a good tolerability profile, regardless of age.

Prolonged-release oxycodone/naloxone in nonmalignant pain: single-center study in patients with constipation.

INTRODUCTION: Opioid treatment for chronic malignant and nonmalignant pain of moderateto-severe intensity is associated with bowel dysfunction leading to constipation; this often requires opioid dose reduction or interruption. Combination opioid agonist/antagonist therapy can restore normal bowel function. A prolonged-released (PR) fixed-dose combination of oxycodone and naloxone has been developed and efficacy has been demonstrated in phase 3 clinical trials. METHODS: This 2-month, retrospective, singlecenter, observational study assessed the effectiveness and safety of PR oxycodone/naloxone in consecutive nononcological patients with constipation and chronic pain despite analgesic treatment; specific subgroup analyses were performed in opioid-experienced or opioid-naïve patients and in age subgroups. Efficacy was assessed by: intensity of pain; bowel function; effective oxycodone/naloxone dose; Patients' Global Impression of Change (PGIC) scale; rescue paracetamol; and laxative use. Safety evaluations were also performed. RESULTS: Of 1,051 patients starting on the oxycodone/naloxone combination (32.0% male; mean age 67 ± 13 years, 53.9% opioid naïve), 1,012 completed 2 months of treatment. Overall, PR oxycodone/naloxone was associated with a significant decrease in pain intensity (P < 0.001), a reduced need for rescue paracetamol (P < 0.001), and PGIC score of "very much improved" or "much improved" in 84.0% of patients. Constipation markedly decreased (P < 0.001) despite reduced laxative use (P < 0.001 vs. baseline). The most frequent treatment-emergent adverse events were somnolence (2.0%), dizziness (1.1%), and confusion (1.0%). Clinical differences in endpoints were seen between opioid-naïve and opioid-experienced patients, and among agestratified groups, but efficacy was similar to the overall population. CONCLUSIONS: Fixed combination PR oxycodone/naloxone was effective and well tolerated in moderate-to-severe chronic pain in patients with constipation, providing analgesia and relief from bowel dysfunction. Consistent efficacy across patient subgroups provides guidance for daily management of chronic pain when therapy options are limited due to bowel dysfunction, regardless of age or previous medication. Supplementary material belonging to this paper is available on SpringerLink.