Optimal Management of Opioid Induced Constipation - Episode 3
A discussion on the use of oral methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic non-cancer pain and the implications for clinical practice.
Gerald Sacks, MD: Peripherally acting µ-opioid receptor antagonists work by blocking the binding of the opioid to the receptor in the gastrointestinal [GI] tract while still allowing the binding of the µ-opioid receptor to the opioid in the central nervous system [CNS]. In other words, they affect the µ-opioid receptors in the GI tract but do not compromise the blood-brain barrier, therefore maintaining opioid-induced analgesia while affecting opioid-induced constipation [OIC]. That’s the beauty of these medications.
When we treat opioid-induced constipation, we commonly start with over-the-counter medications—stool softeners, laxatives, motility agents, etc—but these frequently are inadequate for patients who are taking opioids. It’s best to treat a problem with a medication that’s specifically designed for that problem. In other words, the peripherally acting µ-opioid receptor antagonists are designed to specifically address opioid-induced constipation rather than to produce the result through another mechanism or action. They bind to the µ-opioid receptor and prevent the opioid from causing the constipation in the GI tract, while still maintaining opioid-induced analgesia. If a patient is taking an opioid, they need to be taking an opioid. The opioid is designed to treat their pain, usually through a multimodal anesthesia and analgesia pain-management protocol.
Opioids are just 1 part of this chronic or acute pain treatment. They can cause constipation. I’ve had patients say that the constipation is actually worse than the pain that they were treating with the opioids, in terms of how it affects their function, lifestyle, and the general uncomfortableness of it. By addressing and treating opioid-induced constipation, we can maintain a patient’s functionality. The entire goal of pain management is to have a patient be as highly functional as possible on the lowest dose of opioids possible. By treating and addressing opioid-induced constipation, we can help the patient maintain a healthy, active lifestyle.
Fariborz Rezai, MD, FCCP, FCCM: The phase 3 randomized trial looked at the safety of oral methylnaltrexone [Relistor®] in patients with OIC with chronic noncancer pain. This was a study published a few years ago, in 2018, by Richard Rauck. They looked at patients who received oral methylnaltrexone vs placebo. They primarily looked at any type of adverse events that these patients may have. There were no increased risks of any significant adverse events between the group that received the methylnaltrexone vs placebo. This is good. One of the adverse effects that you think about is CNS effects because these are blocking the effects of opioids in the gut. The reason why you’re giving the patient opioids is so they don’t have that painful sensation and other benefits that the opioids might have. This blocks the effect of the negative effects on the gut. Between the 2 groups of patients, there were no increased or decreased opioid benefits from the anesthesia aspect.
As far as the clinical implications, another study looked at the benefits of using methylnaltrexone. They noticed that those patients, especially the patients who were medically ill with noncancer opioids, had a quicker onset of the bowel movement within 4 hours vs placebo. It was a significant difference. It’s a good tool to have in your toolbox for these type of patients. If they do have OIC, despite using all the laxatives or stool softeners in the world, you’re not going to get that benefit because these patients have decreased peristalsis, decreased fluid secretion, and increased fluid absorption.
Transcript Edited for Clarity