Management of Adverse Effects When Using PAMORAs for Opioid-Induced Constipation

William F. Peacock, MD: What are the most common adverse effects you’ve seen with the PAMORAs [peripherally acting μ-opioid receptor antagonists]?

Conar Fitton, MD: It’s a conversation you’re going to want to have with people. I tie it in when I give the general overview of the pathophysiology in that it does a couple of things. No. 1, people should always be aware of the adverse effects of their medications, but you can also tell them a little about what to expect and why. Obviously, abdominal cramping or discomfort would be the most common one. It isn’t surprising. These patients essentially have had almost an intestinal stunning by the action of the opioid medications, and when you’re restarting peristalsis, it can cause some cramping, so I tell them about that. A small percentage of patients will have some nausea. Abdominal cramping is the most common. Flatulence isn’t uncommon. It shouldn’t be severe. It’s generally very short-acting.

A very small percentage of patients discontinue the medication due to adverse effects, but it shouldn’t be severe. In some of the studies, the percentages were in the 20s, 27% of patients. If it’s mild, it does a few things. No. 1, it’s important for them to know. No. 2, if you don’t tell people this, they’re going to call your office, and your medical assistant is going to quit. Patients should know, and I’m very honest with them about it. Low rates of diarrhea can happen, but we go through each one in detail with percentages because they should know and be aware. Also, if something significant happens, you want them to be aware of it and to call. But I let them know that those rates are very low.

Neel Mehta, MD: Conar hit on that very well. It’s also a good time to talk about when a patient should disclose something that we should be aware of in terms of contraindications. If they have outright obstruction, severe nausea, or vomiting, hopefully that would be apparent to us. But we want to make sure that if somebody has an obstruction, we want to avoid the risk of perforation by using one of these drugs. At the same time, if they’ve had prior risk of disruption to that blood-brain barrier, like if they’ve had brain surgery or significant traumas to the head, there’s a chance that it could trigger some withdrawal. Therefore, we need to be conscious about that as well.

William F. Peacock, MD: Those are excellent points. For an emergency doctor, it’s going to get you in trouble if they might be obstructed. Another thing that’s important here is that it isn’t an adverse event. It won’t take away their pain relief from their narcotic. When I talk to doctors, I hear this all the time. “It’s a narcotic reversal agent. That’s the last thing I want to do with my patient with cancer.”

In the meta-analysis we looked at, we lumped 3 of the randomized controlled trials together. We got a big population, and we looked at pain scores in patients regardless of frailty. We used the WHO [World Health Organization] classification on that. Even if they’re really frail, or if they’re pretty robust but they have severe cancer, having cancer and getting the drug, their pain scores didn’t change at all. They didn’t go up or down, which is exactly what you want. They maintained their pain relief despite the fact that they had relief of their OIC [opioid-induced constipation]. The lack of an adverse event is part of what makes these drugs more attractive.

Transcript Edited for Clarity