Management Options for Nocturia at a Large Urology Group Practice

KOL Interview Management Options for Nocturia at a Large Urology Group Practice David M. Albala, MD,1 David O. Sussman, DO2 1Associated Medical Professionals, Syracuse, NY; 2Delaware Valley Urology, LLC, Sewell, NJ [Rev Urol. 2018;20(3):115–118 doi: 10.3909/riu0820] ® © 2018 MedReviews , LLC I n this key opinion leader (KOL) interview, David M. Albala, MD, Associate Editor of Reviews in Urology, and David O. Sussman, DO, from Delaware Valley Urology, discuss the management options for nocturia used at Dr. Sussman’s large urology group practice. Dr. Albala: Thank you, Dr. Sussman for joining me today. Please describe your practice for our readership. Dr. Sussman: Delaware Valley Urology is a large, singlespecialty urology practice in southern New Jersey. We were approximately 30 urologists and we’ve recently joined with a group in northern New Jersey, New Jersey Urology, so we’re now just about 100 urologists. We are community based, but I’m part a teaching group. We have a residency program as well. So, kind of straddling the fence in terms of being both in private practice and somewhat academically oriented. We are a busy practice as you can imagine. Lots of general urologists, some physicians with erectile dysfunction expertise. I spend a lot of my time with voiding dysfunction, lower urinary tract issues. So, you can imagine that nocturia is a common complaint amongst my patients and we’re quite pleased that we now have an opportunity to treat these people successfully. Dr. Albala: In an earlier discussion, Dr. Lepor and Dr. Dmochowski discussed nocturia as a general medical condition and spent a little time talking about NoctivaTM (desmopressin acetate) nasal spray (Avadel Pharmaceuticals plc, Chesterfield, MO) and its use in various patient groups [Rev Urol. 2018;20(2):53-55]. Because you deal with a lot of voiding dysfunction, perhaps you can outline the type of patient that might come in to your practice with nocturia. Dr. Sussman: Certainly. If you look at the general population of patients that we see with nocturia, the majority come in with other complaints, either symptoms of benign prostatic obstruction (BPO) or overactive bladder (OAB). The percentage of people we see coming strictly for nocturia as a standalone diagnosis is probably no more than 10%. So, the people that we generally see are patients who come in with a constellation of symptoms. If they’re obstructed, they often have decreased flow, hesitancy— the classic BPO symptoms. But usually with nocturia and what we, of course, learned with those patients is, even if we successfully treat their outlet obstruction, their nocturia often is not improved or improved only minimally. The same goes for OAB. These patients often present with urgency and frequency, and nocturia is one of the symptoms. Again, we treat their OAB successfully with either medical therapy or third-line therapy. But their nocturia usually doesn’t improve or only improves minimally. Those are the groups that we see. Nocturia as a standalone condition is certainly not the most common patient presentation that we see. Dr. Albala: Well, many of the patients that you’ve described have co-morbid conditions, and getting an accurate history and physical examination is extremely Vol. 20 No. 3 • 2018 • Reviews in Urology • 115 4170018_00_RIU0820_V3_rev03.indd 115 10/25/18 4:07 PM KOL Interview continued important. Is there anything special that you do in obtaining the history from these patients and in the physical exam? Dr. Sussman: You want to know about their drinking habits. Diuretic use, things of that nature, anything that’s going to change their urinary production. We try to counsel them, of course, about the timing of diuretics, the timing of their fluid intake to lessen nocturia. Clearly, in those individuals with congestive heart failure who have significant lower extremity edema we’re always a bit worried about just treating their symptoms, and we often will get them back to see their primary care physician. We try to do a good job in reviewing their medications. Again, looking at timing of medications and the timing of their fluid intake because all these things will come to bear when treating and improving their voiding symptoms, particularly nocturia. Dr. Albala: Up until Noctiva became available, these patients often could see improvement if they had OAB with anticholinergic medication or, if they had benign prostatic hyperplasia (BPH), alpha-blockers or 5-alpha reductase inhibitors seemed to eliminate their symptoms. But nocturia really is not treated successfully with these medications. Please outline for us how Noctiva can be brought into a physician’s armamentarium to help treat this condition. Dr. Sussman: The major thing to keep in mind is that the etiology of nocturia is typically not the same as the etiology of OAB or BPH. Many of these patients we see who have persistent nocturia after treating their OAB or BPH have nocturnal polyuria. They don’t produce more fluid. They produce more than approximately 30% of their urinary production at night. And we’ve known that those individuals are going to be particularly bothered by getting up at night. Certainly, if you coupled that with their BPH and OAB, it’s even worse. As I mentioned earlier, we can often treat BPH and OAB symptoms moderately well, but the nocturia is the one thing that doesn’t typically resolve; again, because we’re not really targeting the cause of the nocturia, which is nocturnal polyuria. What’s different about Noctiva is it really targets the problem and really gets to the heart of the matter for nocturia by decreasing urinary production in a shortacting manner. Dr. Albala: Noctiva is desmopressin acetate. What makes Noctiva unique compared with the desmopressin acetate that many of us have used over the years and have had problems with hyponatremia? Dr. Sussman: That’s a great question and it’s one of the reasons that if you asked most physicians, urologists in particular, why they haven’t used the traditional forms of desmopressin it’s because by taking it orally, the absorption is hard to predict. And when it was absorbed, it often gave blood levels that were too high or too low. Certainly, when they were too high, we had problems with hyponatremia. What Noctiva has done, and it’s really a kind of a brilliant process, is the inventors have recognized that the dosing needs to be much lower to achieve the results. By also using it as a nasal spray, the absorption and the bioavailability is much more predictable and therefore the incidence of hyponatremia is very low. They have gotten to the heart of the issue with desmopressin in its old form and really have changed it dramatically. We are concerned about, and we do check, sodium levels, but I can tell you thus far— and I’ve treated quite a few patients since the drug was introduced—I haven’t seen it yet. We need to see thousands of patients, but the way the drug is delivered and the much lower dosing, with blood levels in the microgram range, has really changed this medication and allowed us to use it with much greater efficacy and a much lower incidence of adverse events. Dr. Albala: Now, there are some contraindications to using Noctiva, such as patients who have a glomerular filtration rate of less than 50 mL/min, patients who are on steroids, patients who are using loop diuretics. All these patients are really contraindicated by the label. Have you seen this as a big problem, and does it prevent you from using the drug in the majority of patients? Dr. Sussman: I really haven’t. I mean, certainly, the patients that are on steroids, especially if they’re on steroids for the short term, I would wait. Most of the patients that we see are not on chronic steroid use. Obviously, those patients are of some concern. The patients who take loop diuretics are a relative contraindication, and certainly, we worry about those patients with potentially affecting their sodium levels. What I often will do if they’ve been on diruetics chronically and are stable, is check the baseline sodium and then discuss the potential risks of using the lowdose Noctiva and see if they understand the concern and the risk and understand the benefits. So, I really haven’t found that those issues are problematic. Obviously, the patients with significant renal insufficiency are, again, another concern. They should speak with their 116 • Vol. 20 No. 3 • 2018 • Reviews in Urology 4170018_00_RIU0820_V3_rev04.indd 116 10/26/18 3:41 PM KOL Interview nephrologist, discuss it with them to see if the drug is a possibility. I don’t think we’ve really seen that these issues represent a tremendous burden for patients with nocturia. Obviously, there must be caution and discussions amongst the other treating physicians. But for the most part, it has not been much of an issue for me. Dr. Albala: Perhaps you can give us a few little tricks about when patients should take the medication. If they miss a dose, what do you recommend that they do? How quickly do you see the effect of the drug when you prescribe it to a patient? Dr. Sussman: Well, the medication works almost immediately. I tell people they can expect to see improvement in a day or two. They take the medication about half an hour prior to bedtime; it’s one spray in one nostril one half hour before bed. And I tell people that, if you miss a dose, just skip it, don’t double it. There’s no reason for that. And people I see have done well with it. I mean, there’s always some concern about nasal sprays. People get nervous about it but in general it’s been well tolerated. People have done nicely with it with minimal issues with nasal types of adverse events. I remind them to make sure they prime it before they begin to use it, to kind of prime the pump as it were, five times before the first use. And then if they miss taking it for a while, they must re-prime it. But the instructions have been easy. I have them check labs about 3 to 5 days after their first dose and then again about 30 days after the first dose, and see them back in the office to review the results and see how they are doing, adjust their dosing based on their response if needed. Dr. Albala: In the validation studies, we saw close to a 50% reduction in nocturia episodes in patients with a high dose. What is your experience in real life with the patients that you’ve treated? Dr. Sussman: That’s about right. I rarely treat people with nocturia unless it is 3 or more times a night. I mean, most people seem to be okay with 1 or 2 trips to the bathroom a night. The majority of my patients are somewhere in the 3 to 5 range. If you look back on that population, you see about a 50% reduction. I’ve seen generally, they will go from 4 to 2, 5 to 2 or 3. It’s been a little surprising to me as well. I really wasn’t sure what kind of results that I’d see, but the patients have done well. It’s dramatically changed a lot of their lives. They really see a huge difference in their daily activities, their ability to concentrate, for those that are working are not tired at work. I encourage the readership to really talk to their patients about it. Because in the past we’ve pretty much glossed over those people with persistent nocturia either because we didn’t have much with which to treat them or the things we had to treat them were either ineffective or a little dangerous. Noctiva changed the playing field. It’s really incumbent upon us as treating physicians to make sure that we have that discussion and see if people are interested in being treated. Dr. Albala: Noctiva comes in two doses—a 1.66 μg dose and a 0.83 μg dose. The labeling suggests that men that over age 65 years should start at the lower dose. What’s interesting is in the validation study, the safety data was really quite good—only 5 patients out of close to 700 developed severe hyponatremia. And we define hyponatremia as a sodium level less than 125. What’s interesting is that 4 of those patients were on steroids. In your experience, have you seen any hyponatremia or have you seen any sort of nasal discomfort with the drug because that’s been reported at about 5% or 3% incidence between the higher and lower doses? Dr. Sussman: I’ve seen a couple of people who had some nasal discomfort. But what I find is after using the medication for a week or two, it seems to resolve or not be very bothersome. So that has not been, for the most part, an issue in terms of people stopping the drug. I’ve had one patent thus far, an older woman with hyponatremia, it was about 127 or 128. Again, not symptomatic. What had happened was she, unbeknownst to me, had started to take some inhaled steroids for an exacerbation of her COPD. And I think that might have been the issue. So, we had to stop the medication and we’re going to go back and restart it with the understanding that if she does do this again, she must stop the Noctiva. So that’s really been the only patient thus far who has had a problem in terms of hyponatremia. And as I’ve mentioned, she was totally asymptomatic. Dr. Albala: Well, our time is running out. Please summarize what you think are the most important points for a community urologist who’s interested in treating nocturia. What words of wisdom could you give to them with what’s available in the marketplace? Dr. Sussman: The biggest thing to keep in mind is now that we have a medicine that’s effective and well tolerated, it’s important that we ask patients whose nocturia has gone untreated about Vol. 20 No. 3 • 2018 • Reviews in Urology • 117 4170018_00_RIU0820_V3_rev04.indd 117 10/26/18 3:41 PM KOL Interview continued their symptoms and how much it bothers them. It’s going to be a bit of a change to now discussing use of medical therapy for these folks. We didn’t know how to treat nocturia well until recently. We must retool a little bit and talk to these patients in more detail. If physicians spend a few minutes discussing nocturia and the treatments, I think they are going to have a happy patient who’s very satisfied with the response. Dr. Albala: Thank you, Dr. Sussman. The points you’ve made are very important and I’m sure will help our readership going forward. Dr. Sussman: My pleasure. This transcript has been lightly edited for style and clarity. 118 • Vol. 20 No. 3 • 2018 • Reviews in Urology 4170018_00_RIU0820_V3_rev03.indd 118 10/25/18 4:07 PM