New Formulation of Sustained Release Naloxone Can Reverse Opioid Induced Constipation Without Compromising the Desired Opioid Effects

Abstract

This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects.

Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

“…A Phase II, placebo-controlled study of sustained-release naloxone administered to 40 noncancer pain patients with OIC found no serious adverse events in any group and the highest incidence of treatment-emergent adverse events in the placebo group 55. The study evaluated sustained-release naloxone doses of 2.5 mg, 5 mg, 10 mg, and 20 mg with drugs given once daily for 3 weeks and then twice daily for the subsequent 3 weeks (6-week study).…”

“…In a post hoc analysis of a randomized clinical trial of subcutaneous methylnaltrexone for OIC, ~42% of patients could be categorized as responders. Oxycodone/naloxone used for chronic noncancer pain can improve patients’ quality of life, minimize the symptoms of constipation, and does not reduce central analgesic efficacy 55,59,60. Naloxegol has been identified as an effective agent in reducing OIC without compromising central pain relief 34.…”

Efficacy and safety of multimodal analgesic techniques for preventing chronic postsurgery pain under different surgical categories: a meta-analysis

“…Opioids are most commonly used to manage postsurgery pain, but are frequently associated with adverse effects, such as respiratory depression, drug addiction, and nausea and vomiting 8–10 ; therefore, an additional effective analgesic approach must be found. Regional analgesia has been clearly shown to be effective in reducing postsurgery pain, and has been associated with less adverse effects than opioids 11–14 .…”

Assessing the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) in the treatment of opioid-induced constipation

“…In contrast, RCTs for naldemedine or naloxegol tested narrower dose ranges that included the doses approved for marketing: 0.1, 0.2 or 0.4 mg orally daily for naldemedine,7 8 or 12.5 and 25 mg orally daily for naloxegol 9 10. The heterogeneity in dose ranges tested variability may have biased the assessment of the drugs’ efficacy, and hence the interpretation of the results of the network meta-analysis.Variation in trial design and primary or secondary outcome endpoints: Naloxone trials used variable endpoints: three trials assessed bowel function index (BFI),2 3 5 one trial constipation assessment scale (CAS)4 and one trial ‘change in weekly number of spontaneous bowel movements (SBMs)' 6. In contrast, the phase III trials for naldemedine7 and naloxegol9 used the same, US Food and Drug Administration (FDA)-approved primary endpoint for constipation (three or more SBMs/week and an increase of one or more SBM over baseline for ≥9 of 12 and ≥3 of the final four treatment weeks).…”

“…Variation in trial design and primary or secondary outcome endpoints: Naloxone trials used variable endpoints: three trials assessed bowel function index (BFI),2 3 5 one trial constipation assessment scale (CAS)4 and one trial ‘change in weekly number of spontaneous bowel movements (SBMs)' 6. In contrast, the phase III trials for naldemedine7 and naloxegol9 used the same, US Food and Drug Administration (FDA)-approved primary endpoint for constipation (three or more SBMs/week and an increase of one or more SBM over baseline for ≥9 of 12 and ≥3 of the final four treatment weeks).…”