Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is Narrator - ? 00:12 provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 192 I'm your co host, Dr. Kane, Dr. Khyati Patel 00:35 and I'm Dr. Patel, and the title of today's episode is opioids, optional. Journavx, the new acute pain management alternative. So normally, Dr. Kane and I run away from pain management in primary care. But this is exciting, because we're talking about a completely new, unique, non-opioid mechanism drug class and Journavx. So suzetrigine is first of its kind. So we're going to talk about its evidence, safety, place in therapy, the mechanism and additional consideration for use. Dr. Sean Kane 01:08 Who would be a typical patient that might be considered for this type of medication? So we have a 36 year old female who has GERD on a long term ppi, and she's undergoing bilateral bunionectomy procedure, she talks about her post op pain management with the surgical team. She's never been on an opioid before, but she has a family history of opioid dependence, and she'd really like to avoid opioids, if possible. Because of that, she doesn't have any drug allergies. She takes Sprintec as a combination oral contraceptive, and really her question is, what are her pain management options in a post procedure type environment? Dr. Khyati Patel 01:47 Yeah, so we can dive into talking about this new drug, Dr. Kane, Journavx (pronounced jor-na-vix). Again, the pronunciation for the brand name is Journavx and the generic suzetrigine; it belongs to a new pharmacologic class of analgesics called a sodium channel blocker, particularly that NaV1.8 voltage gated sodium channel blocker. Dr. Sean Kane 02:09 And we'll get more into that mechanism in a bit. This was FDA approved in January 2025 so pretty new for moderate to severe acute pain in adults. So it's not indicated for chronic pain. We'll talk about it has a 14 day duration, and it's available as a single film-coated 50 milligram tablet. And again, it's only been studied up to 14 days. So we're not talking chronic pain, but just acute pain for the current indication, yeah. Dr. Khyati Patel 02:35 And generally, the recommended use right now is for the shortest duration possible. So we will talk about the study and how long the drug was used in the study, but definitely no more than 14 days. So Dr. Kane, this channel that we're talking about 1.8 is very specific. Apparently, this sodium voltage gated 1.8 type channel is responsible for transmitting pain signal in the peripheral neurons, and this drug selectively blocks this channel so it prevents the pain signals going from peripheral tissues to spinal cord, specifically like routed from dorsal root ganglions and all the way to the brain. And when Dr. Sean Kane 03:18 we think about sodium channel blockers, Dr. Patel, in my mind, I'm thinking like Novocaine and lidocaine that are blocking, you know, literally all sensation, wherever you inject it, or wherever you topically put it, or even sodium channel blockers, like our anti rhythmics on the heart, right? It turns out that you have a bunch of different voltage gated sodium channels in your body. And actually, when I looked at the mechanism of this where it said V 1.8 so it's sodium, like na with a little v 1.8 I assumed it was like 1.8 millivolts or something like that. But it's actually just, there's nine of these, and this is 1.8 it's like the type of sodium channel that this particular medication is blocking. And there's 1.1 all the way to 1.9 for these voltage gated sodium channels. And suzetrigine actually is really, really, really selective just for the 1.8 so all of the other voltage gated sodium channels out there, the drug basically doesn't interact with them, which is why you don't see some of the effects on the heart or in the brain or having tingling sensations like you would with a lidocaine, something like that. Dr. Khyati Patel 04:22 And science is amazing, right? We've figured out how to specifically go after that one channel itself. Amazingly. Also, this is a novel mechanism and kind of exciting in the pain management world, because this is a non opioid mechanism in that context of acute pain management. So again, we don't have any known abuse or addiction potential associated with Dr. Sean Kane 04:45 that, and we'll talk about the pkpd of the medication in a little bit. But it does go through CYP metabolism, and it does have an active metabolite called M6‑SUZ, and it's a little bit less potent than the parent compound, but does have a different kinetic. Dr. Khyati Patel 05:00 Profile. So before we dive into more details about suzetrigine, let's talk about what's the current problem with the available analgesics. And we know for acute pain management, for moderate to severe pain, we are limited to using NSAIDs, Tylenol or the opioids. Now we know that certain patients cannot take NSAIDs or APAP. There are a lot of contraindications for NSAIDs. It could be that they have renal failure, heart failure, maybe they're on other anti platelet, anti thrombotic drugs, previous history of ulcers and gi bleeds with NSAIDs. So that option is kind of limited for them. For Tylenol, maybe patient has active liver disease or post liver transplant, where we have to kind of be cautious with the use of Tylenol. So those two could be limited for these patients. And then the other option is opioids. And while opioids are okay to be used as short term for acute pain relief. Sometimes patients and providers end up using it for longer than that, and that does increase the risk of abuse and dependence, Dr. Sean Kane 06:10 and we haven't even really touched on the adverse effect profile of these alternative medications. Dr. Patel, but just think about opioids for a second. In elderly patients, if you take an opioid, you're more likely to fall you're more likely to have urinary retention, you're more likely to have cognitive impairment. There's a lot of other things that go along with those, which is why it's kind of interesting to have a different drug with a different mechanism that obviously, hopefully is going to have a different side effect profile that may be advantageous in that, let's say elderly patient population that we don't want them to be at a higher risk for falls and things like that. Dr. Khyati Patel 06:44 Yeah. So back to suzetrigine. You know, it's dosed pretty particularly if you wonder how it's taken. We mentioned that it's available as a 50 milligram, film-coated tablet. However, the initial dose is given as 100 milligrams (two 50 mg tablets) taken on an empty stomach. And then they're very particular about this, so one hour before or two hours after food, it's okay to be taken with clear liquids like black coffee or water and things like that. Dr. Sean Kane 07:13 And we'll talk about it when we get to the PK of the drug. But basically, the intent of this take-on-an-empty-stomach philosophy is that compared to something like Norco hydrocodone acetaminophen, the onset of effect is fairly delayed with suzetrigine, which is why we're taking it on an empty stomach, to expedite how quickly it gets into the blood after that initial dose. Then it's 50 milligrams every 12 hours. You can take it with or without food, because at that point you've already kind of loaded the body up with the drug in the blood. Dr. Khyati Patel 07:40 And we're going to talk about drug interactions in a little bit, but manufacturer is very clear about making sure that, you know, patient doesn't consume any solid or liquid form of grapefruit during the therapy itself. It's a short course, but just to avoid it, Dr. Sean Kane 07:56 and then if two or more doses are missed, you can go back to the 100 milligram single dose, and then go back to the normal scheduled 50 milligrams every 12 hours. And then the manufacturer asks that you don't crush, chew or cut the tablet. Doesn't give a reason. Historically, reasons could be that it changes the PK. It never was studied that way, or even something like It tastes really bad when you do that, and they don't want that bad taste to be experienced by the patient. Dr. Khyati Patel 08:21 Yeah, and then, I mean, maybe it's the way the dosing is designed, that it's available in 50 milligrams. There is no need to cut it. But also, I didn't see a scoring for it, so could be that as well. But diving further into the drug specific let's talk about some of the pertinent pkpds. We sort of talked about the initial dose being higher and the impact of food on the onset of action. But in general, the half life of the parent drug is 23.6 hours, so close to 24 full full day. But that active metabolite we talked about that's a little bit less potent than the parent drug can have 33 hours of half life. So again, longer half life, that means it takes a little bit longer for it to get to steady state. And therefore, again, that justifies the need of that loading dose Dr. Sean Kane 09:11 the drug and its metabolite are very highly protein bound, like more than 95% protein binding. And then in terms of the meals, we kind of alluded to this, but if you take it with a high fat meal, it does delay the time to maximum concentration, called the T max. It doesn't actually change the C max, how high the blood level gets, or the AUC, the total drug exposure, but it does just delay how quickly the drug works, which is why that initial dose is supposed to be taken on an empty stomach an hour before food or two hours after food, so that you can expedite how quickly that medication is getting into the blood. Dr. Khyati Patel 09:47 And in patients who have, you know, moderate hepatic impairment, this does increase both the area under the curve as well as the max concentration. And so again, those modifications. In this patients may be required. Dr. Sean Kane 10:02 And then in terms of drug interactions, we can see three or four interactions, both with inducers and inhibitors. An inhibitor, for example, would be ketoconazole, and an inducer, for example, would be something like rifampin. And basically, if you are using either an inducer or an inhibitor, it might require a dose modification, or you might need to stop or delay taking suzetrigine and tell you that interaction is done. Dr. Khyati Patel 10:28 and the drug is excreted similarly in feces and urine. We didn't really observe any relevant PK changes based on the renal impairment. However, the drug wasn't studied in patients who had EGFR of less than 15. And again, if you look at the pi and the dose modification, it says above 15, there is no need to modify the dose. Dr. Sean Kane 10:50 Now, in terms of the adverse effect profile of suzetrigine, it's actually very well tolerated. Again, we're comparing this to something like an opioid, and we kind of went through some of the side effects of opioids, but with this one, we're seeing roughly a 2% risk of pruritis or itching, compared to about 1.6% with placebo. Muscle spasms were reported 1.3% versus 0.5% with placebo. Increased CPK, so creatine phosphokinase could potentially indicate muscle damage, but maybe not (1.1% versus 0.5% placebo), a decrease in eGFR (2.5%), and then rash 1.1% versus 0.5% with placebo. So we're seeing on most of these adverse effects, maybe a numerical increase, but still very low risk of many of these potential adverse effects. And even with something like the increased creatine phosphokinase in the package insert, it talks about that these patients just had that lab abnormality, meaning that the CPK was more than three times the upper limit of normal. But they never had any signs or symptoms or complications of that, like rhabdomyolysis. They never had to interrupt the study drug because of that lab abnormality. So it's kind of unclear whether some of these things are clinically relevant or not. Dr. Khyati Patel 12:07 and that decrease in EGFR was transient, so about 25 to 50% decrease happened in 2.5% of the patients who were on the active drug. And once the therapy was concluded, the renal function return to the baseline. Dr. Sean Kane 12:22 And then, just generally, you can also look at the discontinuation rate for a medication to give a sense of how tolerable it is. And in the clinical studies, there's less than 1% so point 6% discontinuation rate because of side effects. So this does seem like a fairly well tolerated medication, yeah. Dr. Khyati Patel 12:38 And even just looking at different side effects and the percentages, you know, it's it's not like the 20% pruritus rate or, you know, 13% muscle spasm. It's pretty minute for now. Dr. Sean Kane 12:50 Now, of course, we do have some rare but serious side effects or contraindications precautions that we should be aware of. One is that even though it's rare, remember, rash was 1.1% we do worry about potential for serious allergic reactions like angioedema, respiratory distress. So it can happen with really any medication, but this medication included, Dr. Khyati Patel 13:10 and we kind of talked about the drug interaction, but again, more in the context of who can and cannot be on the drug, the advice is not to use it with strong CYP3A inhibitors. Again, use with moderate inhibitors will require suzetrigine dose reduction, and this dose reduction recommendation is laid out pretty nicely in a table in a PI and again, the reason here is because there will be increased accumulation of suzetrigine and its active metabolite, which can lead to further side effects, Dr. Sean Kane 13:41 and then also avoiding concurrent use with strong or moderate three a four inducers. Again, this is going to mean that the drug won't work as well, so you're not going to get as good of pain relief if you were to do that. Dr. Khyati Patel 13:52 And then, because of that, CYP inhibition via grapefruit juice, manufacturer also recommends to not consume grapefruit items during the therapy itself. Dr. Sean Kane 14:02 Dr. Patel, when they looked at whether suzetrigine causes drug interactions, they identified that it's a weak 3A4 inducer. And kind of interesting, because we don't actually have that many inducers on the market, but it is pretty weak. So because of that, they actually specifically looked at two progestins that are used for hormonal contraception, levonorgestrel and norethindrone, and in both cases, it did not cause any clinically relevant changes to the progestin. But there's a bunch of other progestins on the market, and they can't guarantee that you won't have a clinically relevant drug interaction with those other ones. So because it is a potentially week three, a four inducer A patient should have backup contraception if they're on any of the other progestin so not levonorgestrel or noreth and drone, because they weren't specifically studied, and they can't guarantee that there isn't a clinically relevant drug interaction there, Dr. Khyati Patel 14:54 and because it is not studied in this patient population, a word they use in K. Patients who have severe hepatic impairment or renal impairment, EGFR is defined as less than 15. And then Dr. Sean Kane 15:07 if they have moderate hepatic impairment, just use caution, there is a higher risk of side effects. And then, as we kind of alluded to, this is only really studied in adults, so we don't have any data for pediatric patients that might need to use this medication. Dr. Khyati Patel 15:20 So you know, normally we also look at whether the drug can be used in older patient population. You gave a great example earlier about opioids and having those side effects in older patients. In the studies, about 6.3% of the study population were of age, 65 and above. Currently, there is no guidance if dose needs to be changed. And so as as usual, dose needs to be used in this population as well. Dr. Sean Kane 15:46 And then Dr. Patel, at least in animal studies in rats, they identified that rats had impaired fertility while they were receiving the drug, but then after the drug was withdrawn, that their fertility went back to normal. And at face value, that sounds like you could extrapolate that to humans, but you actually can't. And there's actually a bunch of reasons why in rats that their fertility might be impacted, and in humans it might not be, but either way, it's a potential thing that during the 14 day, course, you might not be able to conceive as well as you normally would, and it's something to just be aware of. But again, we don't have a lot of data to really know for sure. Dr. Khyati Patel 16:25 Yeah, and I think the manufacturer tries to put more attention on the fact that, if you know you're on birth control, make sure you keep those interactions, as you discussed in mind. Dr. Sean Kane 16:35 And then we've alluded to it already, but this currently should only be used for 14 total days a maximum of 14 days. And it's not because at day 15, something bad happens. It just wasn't studied that way. This was acute post operative pain in most studies. With that said, though, on clinical trials.gov, there is a trial looking at the medication for diabetic peripheral neuropathy, so I'm sure at some point we will at least be looking into whether it can be used chronically. But right now, it's for acute management only. Dr. Khyati Patel 17:02 Management only. So we talk about this no more than 14 days of studies done. What are these studies? So let's talk about some clinical evidence. So the majority of the clinical evidence for genovex or zedrazine comes from two randomized, double, blind PLACEBO and active control studies in acute pain situation. Both of these are kind of put into one publication, and thanks to Dr. Kane, we have a reference available in the show notes, so please take a look. But to break down the studies, basically patients who had pain scale of four or more, so our NPRs scale from one to 10, scale of four or more, or verbally, they said that their pain was moderate to severe were included. First trial had patients who underwent abdominoplasty, so like the tummy tuck procedure, and the second trial had patients who went under bunionectomy, so correcting that big toe joint deformity called the bunion. Dr. Sean Kane 18:04 And both cases, in trial one and trial two, they had just over 1000 patients, and the mean pain score was around a seven out of 10. So the range went from four to 10. So these are patients with truly moderate to severe pain immediately after a surgical procedure. And in the trial, what they did was they randomized patients to suzetrigine, placebo, or Norco which is hydrocodone acetaminophen, and they could take that medication for 48 hours with suzetrigine. It's the dose that we talked about, so 100 milligrams initially, then 50 every 12 hours with hydrocodone acetaminophen. This was the five, 325, and the patients took that every six hours, and then, of course, placebo, and then all arms could receive rescue ibuprofen at 400 milligrams every six hours as needed for pain. Dr. Khyati Patel 18:51 And when it came to looking at the efficacy of the drug, they looked at couple of different endpoints. So they looked at the time rate sum of pain intensity difference from baseline to that 48 hour period. And then they also looked at time of onset of the pain relief. So like when did the patient first started to notice that their pain started to subside. So in that abdominoplasty trial, they noticed that the pain intensity difference was 118.4 and this is that suzetrigine group, this 70.1 in the placebo group, and 111.8 in that Norco or the hydrocodone APAP group. Dr. Sean Kane 19:32 And Dr. Patel, the numbers are kind of hard to like clinically understand what they mean, but it's a sum score where they're looking at a bunch of different time points and the time point differences they looked at as well. So you can't directly translate, for example, a 118 score to like going from a eight to a seven on a pain scale, but it does help you understand comparing Group A versus group B versus group C, and with that comparison, what they showed was these. Numerical differences were statistically significant where suzetrigine was better than placebo and it was not different, so not necessarily comparable, but comparable to acetaminophen with hydrocodone or Norco, so better than placebo, not different than Norco, Dr. Khyati Patel 20:17 yep, and that was true on the statistical level as well. And when it comes to the onset of pain relief, they looked at medium time to meaningful pain relief, which they define as two or more point reduction in that pain score, which was 119 minutes in the suzetrigine group versus 480 minutes in the placebo group. Dr. Sean Kane 20:38 And Dr. Patel in the article they actually did not report median time onset to pain relief with suzetrigine versus Norco. Probably it wasn't different, but they didn't report the number. So we don't know. Dr. Khyati Patel 20:50 Looking at the similar end points in the bunionectomy trial, the time rate, sum of pain intensity difference from baseline to 48 hour, that was 99.9 in the suzetrigine group, 70.6 in the placebo group, and 120.1 in the Norco group. So again, higher the number, the better the result. Dr. Sean Kane 21:14 And from a statistical standpoint, suzetrigine was better than placebo, but it was not better. So Norco was actually superior to suzetrigine when they did the comparison. So in the abdominoplasty article, we showed that it was more or less similar to Norco better than placebo. In the bunionectomy trial, Norco is actually a little bit better, but suzetrigine was still better than placebo, Dr. Khyati Patel 21:39 and then again, that two or more point reduction in the pain scale with the zadrogen it was achieved at 240 minutes versus 480 minutes with the placebo. And again, no comparison with the hydrocodone Tylenol group was available, Dr. Sean Kane 21:56 as we alluded to, in terms of rescue therapy, patients were eligible to receive ibuprofen as rescue therapy. And basically, almost everyone we're looking at, more than 80% of the time, they used rescue ibuprofen. And at face value, you might say, well, that's bad because the drug isn't working, but in real life, clinical practice, it actually mimics what would normally happen after a surgical procedure, that you take a medication, and if it's not working, you have something for breakthrough pain. In that case, probably when we use suzetrigine, we should mimic that same type of practice where you take the medication suzetrigine, and then if it isn't working, you have an NSAID or even Tylenol as a rescue therapy that you can add on top of it, Dr. Khyati Patel 22:36 and then Dr. Kane. That's a summary of our efficacy outcomes. But if you look at the safety outcomes. We discussed those adverse events before, I just wanted to highlight that nearly all the safety data. So the side effects we talked about comes from these two trial plus their open label phase that extended no more than 14 days. So we talked about that was pruritus, muscle spasm, increased, CPK, that transient decrease in EGFR that was noticed, and then rash, and Dr. Sean Kane 23:04 again, all of these are we're looking at like 2% or less incidence rate. And in the placebo arm, we're looking at point five to 1% so really not that much of a numerical difference. And for the most part, this did not result in a discontinuation of the drug therapy. Dr. Khyati Patel 23:21 So Dr. Kane, the real question now is, because it's a new drug, it's brand name, it's novel mechanism. What are we talking about? Money buys? Dr. Sean Kane 23:30 I think you already know the answer to this. It's more about how expensive is it going to be? So if you look at the AWP, so the average wholesale cost, which is always inflated, meaning that this is like the most that you'll ever pay for it. It's $18.60 per tablet versus in a generic opioid, you're looking at way less than $1 you're looking at maybe 10 to 15, maybe 20 cents per per day for an opioid tablet, so obviously vastly more expensive than Tylenol, ibuprofen and a typical opioid that you would prescribe, right? Dr. Khyati Patel 24:02 And if you look at good RX, a 14 day, course, because, again, we're not doing that, more than 14 days comes out to be for 50 to $500 you know, cash price. So that's, that's hefty. Dr. Sean Kane 24:14 And again, from the drug in all defense of the drug manufacturer, it is a new medication with a novel mechanism. But on top of that, if you could potentially have a patient not take an opioid, I'm sure that one way that it could be sold is that by avoiding the opioid, now, you avoid the fall, or you avoid the cognitive impairment or the urinary retention that requires a Foley catheter insertion, or whatever, the avoidance of the opioid, I think, is probably where the manufacturer likely is excited to talk about if, based on the surgical procedure, you either don't need the opioid at all, or you need less of it than you normally would without suzetrigine, Dr. Khyati Patel 24:49 so with us discussing, you know, how the drug is taken, the PK differences and nuances, the safety issues as well as efficacy, what is the best place in the. Therapy versus that Regine. And off the bat, I can tell you that even though this is a new option available as of January this year, no guidelines have still adapted that in their recommendation, one thing is clear from the CDC guidelines, in that post surgery acute pain management, they are prioritizing the use of non opioid measures, so maybe that guideline wording already supports the use of this drug, but that's also dependent on a Dr. Sean Kane 25:30 lot of different factors, and even on top of avoidance of opioids, just the concept of multimodal analgesia, in terms of picking more than one drug that has different mechanisms that can treat pain in different facets, this medication totally does that. So we don't exactly know where the place in therapy is going to be in these guidelines, but probably it's going to be either an alternative or an adjunct to your NSAIDs, your Tylenol and or your opioids for moderate to severe pain, especially when used for 14 days or less, because that's how it was currently studied. From a cost perspective, this is where it's going to get tricky in terms of, is it worth the cost? Is insurance cover or not? And that's probably going to be one of the bigger factors to consider. Dr. Khyati Patel 26:14 And as you mentioned earlier, too, Dr. Kane, we are doing this multimodal approach, and based on the study population, too. Most of them were allowed to do that rescue with NSAIDs. In real life, you know, NSAIDs are not tolerable or contraindicated. You could do rescue with Tylenol as well. So you're looking at Cesaro gene, not just by itself, you know, in combination with NSAIDs or Tylenol. Dr. Sean Kane 26:37 And then, especially, like in our patient case, someone who's intentionally trying to avoid opioids. This you might be more excited to use this, especially if you have a painful surgical procedure where you normally use opioids, but now you don't want to. This could be an option for those patients, Dr. Khyati Patel 26:52 right and then just again. To keep in mind that this is only approved for the acute 14 days or less duration, so we are not recommending this drug for chronic pain. It's not yet made available for neuropathic pain treatment or any kind of long term or pain control, or even pain control for those who have hepatic impairment, severe hepatic impairment. Dr. Sean Kane 27:16 Dr. Patel, it's very usual that a new medication that comes to the market, has all of these like niche areas that it's only been studied in with the desire for expansion of that. And if we think back to like doacs, for example, when the doacs first came out, they were basically just for non valvular afib, but then they expanded into VTE and a variety of other indications as well. So we need to obviously give it time, but I guarantee you the or I hope the manufacturer is very interested in doing a knee replacement trial, or a trial looking at opioid reduction in patients that need opioids after a surgical procedure, or even looking at reducing opioid complications by using this medication versus placebo. So there's so many different facets that could be studied, and we just need to give it some time. Dr. Khyati Patel 28:04 Yeah, time will tell exactly that's right. So returning back to our patient case. Remember, this was a relatively young female who was undergoing a bunionectomy procedure and kind of wanted to discuss her pain management strategy post the procedure. Patient is opioid naive. But again, as we mentioned, patient is concerned about opioid dependency. So seems like, you know, considering patient shared decision making, patient wants to avoid taking the opioids. Dr. Sean Kane 28:31 And then, in terms of her current drug therapy, she's on a PPI chronically. And then the more important thing is that she's taking Sprintec, and that is a progestin containing oral contraceptive. And that's relevant because the progestin in Sprintec is norgestimate, and that is not one of the ones that was studied with the drug drug interactions from the manufacturer. So that is not levonorgestrel or norethindrone. So for that reason, if this patient is going to take suzetrigine, then they're going to have to have non‑hormonal contraceptive during treatment, and then 28 days after treatment, because of the theoretical risk of that CYP induction occurring. Dr. Khyati Patel 29:10 So yeah, I mean, you brought up suzetrigine, and that's a very valid option as a non-opioid option for her moderate to severe pain post procedure. But we'll have to be careful with that drug interaction. With her Sprintec use, and if she needs to use suzetrigine for longer, because currently, you know, it's only used 14 days or less, we will have to bring in other analgesics like Tylenol or NSAIDs to help out. Talking about NSAIDs, though we do have this patient on GERD treatment long term PPIs, we know that NSAIDs may worsen those symptoms. Again, by itself, it may not be enough if patient is experiencing severe pain, so maybe patient may need some additional help or adjunct therapy, and then again, depending on the or the procedures that you. Do. There's some evidence that NSAIDs do interfere with that post procedure, soft tissue or bone healing. And so I've noticed some ortho providers suggesting against the use of NSAIDs in that post procedure period. Dr. Sean Kane 30:16 And then again, maybe the patient doesn't even need anything, and they can just have nothing or Tylenol, NSAIDs we kind of went through. If we've exhausted those options, we could still consider an opioid with acknowledging the patient's concerns. So Tramadol, for example, could be an opioid that still has misuse and abuse potential, but that is still one option, or a very short duration, like a five day duration, or a three day duration, the risk of misuse and abuse is directly correlated to dose and duration of time, so low dose, short duration of time may be helpful there. Dr. Khyati Patel 30:50 So again, this is not a straightforward answer. It's really just a patient provider discussion, but it's great that patient is wanting to discuss that before going under the procedure. And so we have, you know, more options than just what we had previously. And that was the point of this discussion in itself. Dr. Sean Kane 31:08 So Dr, del to kind of wrap up and summarize some of the key points from today's episode. Suzetrigine is a first‑in‑class voltage gated sodium 1.8 channel blocker that's approved for short term use, so 14 days or less for acute pain relief in adults with moderate to severe pain; it's non‑sedating and does not have any dependence or abuse potential associated with it, and Dr. Khyati Patel 31:31 the drug is taken as a whole pill, without cutting, crushing or chewing, following a particular dosing schedule where that first dose is taken on an empty stomach, and it's a higher dose, and then their subsequent doses are lower doses every 12 hours, can be taken with or without food. Dr. Sean Kane 31:48 And then, from a side effect standpoint, it's very well tolerated. We're talking very low single digit incidence rate of adverse effects. But those adverse effects can include pruritus, or itching, muscle spasms, increase in Cpk rash and then a transient and reversible EGFR decrease. Dr. Khyati Patel 32:06 And as we talked about the safety issues, interaction wise, it does go through CYP3A metabolism. And so there are some significant interactions with the CYP3A inducers and inhibitors to keep in mind. So again, use with strong inhibitors and moderate to strong inducers is not recommended. However, if we need to use it with moderate inhibitors of CYP3A, the suzetrigine dose can be adjusted, Dr. Sean Kane 32:33 then it is a brand new medication. So the guidelines haven't really weighed in yet. And to be honest, we don't have as much literature is we might like to have to help inform those guidelines, but right now, it's placed in therapy is for moderate to severe acute pain in adult patients, and this is either going to be as an alternative or in addition to NSAIDs and Tylenol, and then ideally, either an alternative or in place of an opioid. But again, depending on the patient and how bad their pain is. This might be more of a patient specific approach based on all of the factors that we discussed. So Dr, tell for the listeners if they want to read the phase three trial. We have a reference in our show notes at HelixTalk.com this is episode 192 we're on iTunes and Apple podcasts. We love the five star reviews there, and if you want to get an email whenever new episodes come out, you can subscribe to our mailing list again at HelixTalk.com so with that, I'm Dr. Kane and Dr. Khyati Patel 33:29 I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 33:32 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 33:43 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.