The role of opioid receptor antagonists in the treatment of opioid-induced constipation: a review

Opioid-induced constipation (OIC) is associated with negative impact of opioid analgesics on opioid receptors located in the gut wall. Until recently, OIC was treated symptomatically only, with different laxatives which did not target the pathophysiology of OIC. Recently, several opioid receptor antagonists have been introduced in the treatment of OIC. Methylnaltrexone (MNTX) is a peripheral mu-opioid receptor antagonist for subcutaneous administration, which does not evoke symptoms of opioid abstinence. MNTX is indicated for patients with OIC who are not amenable to therapy with oral laxatives. In clinical trials, the effectiveness of MNTX assessed as its ability to induce spontaneous bowel movement, is 50%-60% of treated patients; MNTX demonstrates significant superiority over placebo. Another product is combination of oral formulation of prolonged release oxycodone and prolonged release naloxone (PR oxycodone/PR naloxone), indicated for patients who require opioid administration for chronic pain and have already developed OIC, and for those who need opioid therapy and take the drug to prevent OIC. Naloxone administered orally displays local, antagonist effects on opioid receptors in the gut wall, negligible systemic bioavailability, and significantly reduces the oxycodone constipating effect. PR oxycodone/PR naloxone has similar analgesic efficacy, but causes less constipation and less laxative consumption in comparison with patients treated with oxycodone alone. Both products are expensive, therefore their administration should be carefully considered. On the other hand, uncontrolled OIC and the necessity to perform rectal invasive procedures (enema, manual evacuation) lead not only to increased health care costs, but most importantly, cause severe patient suffering.