Q&A: How Will Suzetrigine Impact the Pain Management Landscape?
A discussion on the new nonopioid selective NaV1.8 pain signal inhibitor with Madison Irwin, PharmD, BCPS.
Suzetrigine (Journavx), a nonopioid selective NaV1.8 pain signal inhibitor, became the first new class of medicine to treat acute pain in more than 20 years when it was approved by the FDA in January. Data from a phase 3 program evaluating the therapy showed it resulted in statistically significant improvement in pain intensity with a favorable safety and tolerability profile.1
Q&A: How Will Suzetrigine Impact the Pain Management Landscape? / BillionPhotos - stock.adobe.com
Drug Topics® recently sat down with Madison Irwin, PharmD, BCPS, clinical pharmacist specialist in palliative care at University of Michigan Health and a clinical assistant professor at University of Michigan College of Pharmacy, to discuss the importance of suzetrigine’s approval in the pain management space, potential challenges or barriers in its adoption, and important things about suzetrigine that pharmacists should be aware of.
READ MORE: What Pharmacists Need to Know About Suzetrigine for Pain Management
Drug Topics: Can you discuss the importance of suzetrigine’s approval in the pain management space?
Madison Irwin, PharmD, BCPS: In terms of its importance, this is the first agent with—I'm going to say new with a caveat—a new mechanism. We haven't had anything come to the market since the '90s, when we had some COX-2 selective NSAIDs [nonsteroidal anti-inflammatory drugs] come to the market. It's kind of the first new thing for a long time in this space. It is working by blocking a specific subtype of voltage gated sodium channels called naV1.8. These are kind of specifically expressed on peripheral sensory nerves. Through a lot of preclinical studies going back many years, it's been demonstrated to play a role in nociceptor or pain signaling. We have non selective sodium channel blockers, so things like lidocaine for example, and these can be useful as analgesics in the acute pain space. But because they are non-selective, they have pretty significant, or can have pretty significant, side effects and risk for toxicity. Primarily we're thinking about CNS [central nervous system] toxicity and cardiovascular risks. One of the ideas behind targeting these specific sodium channels is that they are not expressed in the brain and spinal cord, so that should theoretically reduce the risk of CNS toxicity that we can see with our non-selective sodium channel blockers.
When we're thinking about in comparison to opioids, which have totally different mechanisms of action, because this does not work in the CNS centrally, we don't expect it to have any abuse potential or addiction potential. That is one of the big selling points of this particular drug. I think it's exciting to have another analgesic option available in the acute pain space. Right now, we have our NSAIDs, opioids and local anesthetics like the lidocaine. Each of those have their own risks and limitations of use based on patients’ renal and hepatic function and other comorbidities. This expands that arsenal. It seems to be pretty well tolerated and that's always good to see in terms of the side effect and safety profile. It does seem like something that we'll be able to use in some stages of hepatic impairment as well as renal impairment. Those are always populations that I'm thinking about what options I have for them.
Drug Topics: Do you think there will be any challenges or barriers in the adoption of suzetrigine?
Irwin: I think with any new drug that comes to the market, it’s going to take some time for people to become familiar with and what to expect. Insurance coverage is oftentimes going to play a role in whether or not something's available. Additionally, whether you know what the uptake for institutional and hospital formularies look like can impact its uptake. To me, and this may have more to do with the kind of space that I practice in, but the biggest question is what its impact on chronic pain will be. One of its selling points is that it really works peripherally. It does not work in the central nervous system, in the brain or the spinal cord. While that makes sense for managing acute pain, some types of chronic pain have a different mechanism, and some of those things are more centrally mediated. I would worry that perhaps this medication would not provide as much benefit just based on the mechanism of that pain.
From what I've been able to gather, there's some phase 2 data out there looking at a couple of different chronic pain conditions, like peripheral neuropathy and sacral radiculopathy. There does seem to be some signal of benefit. That that will remain to be seen, but that's kind of the big question on my mind that will help better establish what its place in therapy is.
Another challenge is that this is an oral medication. Particularly thinking about the acute pain space and perioperatively, we don't always have oral access. People aren't always able to take oral medications. The fact that it's only available as an oral medication and doesn't have an IV [intravenous] or an injectable version would probably be a limitation. It does look like Vertex, and I imagine others working on these kind of selective sodium channel blockers, are looking at developing IV formulations. I would say that is something that stands out to me as potentially a barrier, specifically wanting to be able to use this in acute pain.
Drug Topics: Are there any important things about suzetrigine that you think pharmacists should be aware of?
Irwin: I would say in terms of drug interactions, it is primarily metabolized by cyp3a4, which metabolizes a lot of other medications. There's definitely potential for pretty significant drug-drug interactions. It's labeling indicates that it is contraindicated with strong cyp3a4 inhibitors. So, just something to be aware of, because even if someone's on a strong inhibitor, if they're on moderate inhibitor that may require some dose adjustments. It can be used in some degree of renal and hepatic dysfunction, so the manufacturer does provide us with some dose adjustments for kind of initial, earlier stages of hepatic impairment, but it has not been studied in more advanced hepatic impairments, so would not be recommended there.
As far as other things to think about, especially from a counseling perspective, if an individual is receiving suzetrigine and they are also using contraceptives with some specific progesterone, So any progestins other than levonorgestrel and norethindrone, they will need to use an alternative contraceptive method for 28 days after discontinuing the medication. That would be an important thing to be aware of.
Less on the drug interaction side of things, but more on the tolerability, based on the data that we have in the label and what you're able to find, it does seem to be pretty well tolerated. I was pleased to see really no cardiovascular side effects reported, and that seems to be supported by what we see with the preclinical data in terms of side effects that were reported in the clinical trials. Largely things like skin rash, muscle spasms, all pretty low incidence. There did seem to be some occasional reports of elevated creatine phosphokinase levels. But these were not elevated to kind of clinically significant extent.
READ MORE: Nonopioid Pain Management
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