Using PAMORAs for OIC Treatment

Gerald Sacks, MD: Naloxegol is also a peripherally acting µ-opioid receptor antagonist. It’s used to treat opioid-induced constipation [OIC]. The issue with this medication in my practice is that it requires metabolism through the cytochrome P450 system. I frequently have patients who are taking numerous other medications. Sometimes more than half their medications require metabolism through the cytochrome P450 metabolic steps. If I overload those steps, then the patients may have difficulty metabolizing their medications, including metabolizing their opioids.

The medication naloxegol can be an effective treatment for opioid-induced constipation. But if I have patients, taking protease inhibitors or certain antibiotics that require the cytochrome P450 metabolic step for their metabolism, and the patient also takes opioids that go through those same metabolic steps, then I don’t want to overload the metabolism—the hepatic metabolism—of these medications and potentially increase the effects of the opioids. Although naloxegol is an appropriate choice for some patients, it may not be an appropriate choice for patients who are taking medications that are also metabolized through the same cytochrome P450 metabolic steps in the liver.

Fariborz Rezai, MD, FCCP, FCCM: One of the things we do as physicians and health care practitioners is to use a drug or treatment based on evidence-based medicine from robust studies. Methylnaltrexone did have some strong studies for patients with advanced illness or pain caused by active cancer and also for noncancer opioid patients. Those studies monitored bowel movements within 4 hours of administering the drug. Amlodipine and naloxegol didn’t have similar studies, so they had no end point relief within 4 hours. They’re not indicated for advanced illness or by pain caused by active cancer. Based on that, I use what’s been studied and what’s been approved by the FDA and deliver standard care.

I’m more familiar with inpatient settings because that’s what I do as an intensivist. With the patients who are intubated, who are on opioid drips, we tend to use a lot of fentanyl drips. Most of them are located throughout the country and throughout the world. But with the COVID-19 pandemic, many of these patients were intubated for a long period of time and developed OIC. Not everybody develops OIC, but there are patients who do. It’s important to have that part of your differential because part of evaluating an ICU [intensive care unit] patient is doing our system by system. When it comes to GI [gastrointestinal] system and your patient has not had a bowel movement for a prolonged period of time, that leads to discomfort for the patient. This decreases their opioid requirements, unfortunately.

On top of that, it can cause other issues for a patient. They can have ischemic bowel syndrome, and they can have a perforation. These are the things you don’t want to do for your patient. You don’t want to cause any harm from the benefit that they’re getting from being intubated and being comfortable. By the same token, you don’t want to have OIC, and that has to be recognized on a daily basis. When you do your rounds every day you assess: Did the patient have a bowel movement? Are they on an appropriate bowel regimen? If they are, why aren’t they moving their bowels? Is there something going on? Do they have an obstruction? Do they have OIC? You have to do a full assessment and treat them appropriately. Using something like methylnaltrexone, which doesn’t cross the blood-brain-barrier, I’m not going to lose the analgesia effect. I want to lose that effect for a patient who is intubated. I don’t want them to experience that discomfort of being on a ventilator and just hungry for their breath. That’s not what we want to do as health care practitioners. You don’t want to minimize that, but you want to minimize the effect of the opioids on the immune receptors in the gut. If you can do that, it’s a win-win. The patient will have a bowel movement, and you won’t affect the analgesic effects of fentanyl, for example, for patients on a ventilator.

Transcript Edited for Clarity