Oral naloxone reverses opioid-associated constipation

Abstract

Opioid-related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid-associated constipation in an intraindividually controlled manner. Twenty-two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention ('control period'). Then, oral naloxone was started and titrated individually between 3x3 to 3x12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, patients were observed for further 6 days ('naloxone period'). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the 'naloxone period' due to death, operation, systemic opioid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day 'naloxone' compared to the 'control period', the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the 'naloxone period' was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

Combined oral prolonged-release oxycodone and naloxone in chronic pain management

“…As the studies in non-cancer pain are limited to a dose range of up to 80/40 mg of PR OXN, further research on higher doses would be recommended [5,6,[14][15][16]. New strengths have been developed recently, which may allow for the use of larger doses.…”

“…The limited systemic availability of N avoids blocking the desired central analgesic effects of opioids. A number of pioneer studies have assessed the ability of oral immediate release N, also showing some evidence for slightly reduced analgesic efficacy, and intestinal withdrawal symptoms [5].…”

Opioid Induced Constipation

“…Naloxone blocks opioid intestinal receptors and has low systemic bioavailability (2%) due to a marked hepatic first-pass effect. In patients with chronic pain, oral naloxone improved symptoms of laxation (24), but because of its very narrow therapeutic index, doses that reverse gut symptoms can often cause reversal of analgesia (25). However, there has been a resurgence of interest in naloxone in a prolonged-release preparation, which shows evidence of analgesic efficacy and safety when used in combination with oxycodone (prolonged release) for moderate-to-severe chronic pain (26) and improved bowel function when compared with oral oxycodone (prolonged release) alone (27).…”

Management of opioid-induced constipation

“…Naloxone is a central and peripheral acting opioid receptor antagonist that is efficacious for treating OIC (Meissner et al, 2000). This medication can be administered separately from opioid medications or as a premade fixed dose combination tablet.…”