Efficacy and safety of naloxegol for opioid-induced constipation assessed by specific opioid medication, opioid dose, and duration of opioid use.

OBJECTIVE: Efficacy and safety of naloxegol, a peripherally acting µ-opioid receptor antagonist that significantly reduces opioid-induced constipation (OIC), were assessed for patient subgroups defined post hoc by baseline maintenance opioid characteristics. DESIGN: Post hoc, pooled analysis of data from two 12-week, randomized, double-blind, placebo-controlled, phase 3 studies. SETTING: Two hundred fifty-seven outpatient centers in the United States and Europe. PATIENTS: Patients with noncancer pain and OIC. INTERVENTIONS: Naloxegol (12.5 or 25 mg daily) or placebo. MAIN OUTCOMES MEASURES: The primary efficacy endpoint was the proportion of patients meeting response criteria at 12 weeks: at least three spontaneous bowel movements (SBMs)/wk and an increase from baseline of at least one SBM for ≥9 of 12 weeks and ≥3 of the last 4 weeks. No adjustments were made for multiplicity; all p values are descriptive. RESULTS: This analysis included 1,337 patients. Increases in the proportion of patients who achieved response at 12 weeks were observed with naloxegol 25 mg versus placebo in patients taking maintenance oxycodone, hydrocodone, morphine, or fentanyl (p ≤ 0.038); patients taking either ≥120 or <120 morphine-equivalent units at baseline (p ≤ 0.032); and patients treated with their current opioid for >6 months (p ≤ 0.035). Efficacy results were less robust with naloxegol 12.5 mg versus placebo. Adverse event incidences were generally comparable across treatment groups, regardless of opioid dose or duration of therapy but were numerically higher with some specific baseline opioids. CONCLUSION: In this post hoc, exploratory analysis, naloxegol 25 mg showed similar efficacy in treating OIC regardless of maintenance opioid type, dose, or duration of opioid use at baseline.

Drug-drug interaction between NSAIDS and low-dose aspirin: a focus on cardiovascular and GI toxicity.

INTRODUCTION: The aging of the population in the US and other countries means that a large number of people will likely take NSAIDs for the relief of pain and low-dose aspirin (LD-ASA) for cardioprotection. However, the cardioprotective value of LD-ASA can be compromised in patients who take NSAIDs concomitantly, because some NSAIDs competitively bind to critical amino-acid residues on cyclooxygenase (COX) enzymes and interfere with the mechanism of antiplatelet activity of LD-ASA. AREAS COVERED: A review of the literature was conducted to provide an overview of current issues surrounding the concomitant use of NSAIDs and LD-ASA, to explore potential mechanisms for this drug-drug interaction and to consider current and future treatment options that may mitigate the risk associated with their concomitant use. EXPERT OPINION: NSAIDs offer effective pain relief for the most common forms of pain, such as low back pain, musculoskeletal pain associated with arthritis, postsurgical pain, headache, acute pain syndromes, menstrual pain and dental pain. The development of NSAID formulations that offer effective pain control with fewer or less serious adverse effects due to interference with ASA would be a valuable medical advance. Several promising treatment options and regimens may be available in the future.

Efficacy and tolerability of cyclobenzaprine extended release for acute muscle spasm: a pooled analysis.

OBJECTIVE: To assess the efficacy and tolerability of once-daily cyclobenzaprine extended release (CER) 15 and 30 mg in relieving acute muscle spasm. METHODS: This is a pooled analysis of 2 randomized, double-blind, placebo-controlled, parallel-group studies of identical design. Adults with local muscle spasm associated with neck/low back pain were randomized to treatment with once-daily CER 15 (n = 127) or 30 mg (n = 126), cyclobenzaprine immediate release (CIR) 10 mg 3 times daily (n = 123), or placebo (n = 128) for 14 days. Primary outcome measures were the patient's rating of medication helpfulness and physician's clinical global assessment of response to therapy at day 4. RESULTS: Of 504 patients, 330 (65.5%) completed the studies. Significantly greater improvements in patient's rating of medication helpfulness were reported with CER 15 and 30 mg versus placebo at day 4 (P < 0.025). No differences were reported between groups in physician's clinical global assessment. Significantly greater improvements (P < 0.025) were noted in patient-rated secondary measures versus placebo: relief from local pain at days 4 (CER 30 mg) and 8 (CER 15 and 30 mg), global impression of change at days 4 and 8 (CER 30 mg), and restriction of movement at day 4 (CER 30 mg). Improvements with CER 15 and 30 mg on most efficacy measures were similar to CIR. There was less reported daytime drowsiness with CER 15 and 30 mg than with CIR (P < 0.05). Most adverse events (AEs) were mild in intensity. The most common AEs for all groups were dry mouth, constipation, dizziness, headache, and somnolence. The rate of somnolence reported as an AE was lower (P < 0.05) with CER 15 (0.8%) and 30 mg (1.6%) than with CIR (7.3%). CONCLUSION: Once-daily CER was effective in relieving acute muscle spasm based on patient's rating of medication helpfulness at day 4 and was generally well tolerated with a low rate of reported somnolence.