Hot New Drugs in Palliative Care: Max Stevenson, Alex McPherson, and Nisha Iyer

Eric 00:14

Welcome to the GeriPal Podcast. This is Eric Widera.

Alex 00:19

This is Alex Smith.

Eric 00:20

And Alex, we’re going to be talking about hot new drugs in palliative care.

Alex 00:24

Hot new drugs.

Eric 00:25

Who is with us to talk about this?

Alex 00:26

We are delighted to welcome Max Stevenson, who is a palliative care pharmacist at The Ohio State University. Wexner Medical Center. Max, welcome to the GeriPal Podcast.

Max 00:35

Thank you.

Alex 00:36

We’re delighted to welcome Alex McPherson, who’s a palliative care pharmacist at MedStar Health in Washington, DC. Is this the first time we have had a like parent-child on?

Eric 00:47

Are you related to Mary Lynn McPherson?

Alex McPherson 00:53

No.

Alex 00:54

Oh, you’re not?

Alex McPherson 00:54

I don’t know what you’re talking about…No, I’m just kidding (laughter)

Alex 00:56

Okay, good. You had me there.

Alex 00:58

I was like, what did I step into? No, no, no. All right. We had your mom on previously.

Alex McPherson 01:04

I had to make sure I didn’t pick her song. Are you kidding me? (laughter)

Alex 01:09

We’re also delighted to welcome back Nisha Iyer, who is a palliative care pharmacist who works with Eric and I in San Francisco. Nisha, welcome back.

Nisha 01:17

Thank you for having me.

Eric 01:18

Nisha, your claim to fame is you were on one of our highest listened to podcasts about gabapentinoids.

Nisha 01:25

I am so honored. That was the first time I’d ever done a podcast. Uh, I was fresh outta residency. Eric and Alex just reached out to me, hey, you wanna try this podcast? I was like, why not?

Alex McPherson 01:34

And here we are.

Eric 01:35

Let’s do it.

Alex 01:36

Here we are.

Eric 01:37

Okay, so, we’ve got a lot to talk about. Hot new drugs. I can’t even pronounce a couple of ’em.

Alex 01:43

Mm-hmm.

Eric 01:43

Uh, but they’re gonna range from suzetrugine all the way down to Dora’s and GLP-1s in palliative care. But before we do, Alex, I think you have a song request for Alex.

Alex McPherson 01:56

I do. I’m requesting Your Love Is My Drug by Kesha.

Eric 02:02

Is there a reason you picked this song?

Alex McPherson 02:04

One, because as the palliative care pharmacist, it felt like, you know, the only responsible choice here. And also I wanted to hear Alex sing it and play it. So let’s do it.

Alex 02:16

Yeah. Challenge accepted. This is a little different from Kesha’s version, but here we go. Here’s a bit.

Alex 02:23

(singing)

Eric 03:19

That was awesome. Thank you.

Max 03:22

Yes.

Alex McPherson 03:22

Standing ovation.

Alex 03:24

Fun one. That was fun. Thank you, Alex.

Eric 03:27

Can I just highlight how awesome this is that we have 3 amazing palliative care pharmacists on this podcast?

Alex McPherson 03:33

Yeah.

Eric 03:34

Maybe at the end, I’m going to do my lightning round question then, just to prepare you, why every palliative care team should have a palliative care pharmacist on it. So just Just think about that. That means listeners, if you want the answer, listen for the end of the show notes.

But we got a lot to talk about today. Hot, hot new drugs in palliative care. I’m gonna quote unquote new, ’cause I think some of these may not be so new, but should be. Uh, Max is excited to talk about one of ’em, but I’m gonna start off the topic on suzetrogene. What’s the non-generic name for that?

Alex McPherson 04:13

Ternavix.

Eric 04:14

Ah, so we’re gonna use suzetrogene, the generic name. What the heck is this?

Nisha 04:22

It came to market pretty recently and everyone was excited because there hasn’t been a new pain medication on the market in many, many years. And it is FDA approved currently for moderate to severe acute pain. And it was studied in 2 situations. So it was studied in post-op pain in abdominoplasty and bunionectomy.

Eric 04:47

Not really a palliative care population there.

Nisha 04:49

Not really a palliative care population there. And everyone’s super excited because that’s how it initially came out. But what else can it be used for? Can we use it as another non-opioid alternate?

Eric 05:01

Yeah.

Nisha 05:01

So that’s kind of the gist there.

Eric 05:02

And you call it a non-opioid, Max. How does it work?

Max 05:06

Yeah, so it, it’s essentially a sodium channel blocker that’s very selective. So instead of something like mexiletine or lidocaine where it kind of blocks all those sodium channels, there’s very specific ones that are responsible for pain signaling, especially in the periphery. So this targets that one, one of the pain signaling specific sodium channels. So theoretically can be very, very helpful, especially if there’s some kind of neuropathy component too.

Eric 05:33

Does it have any of the same side effects as mu opioid receptor agonists?

Max 05:38

Nah, nah. I mean, it’s, it’s purely just for—

Alex McPherson 05:42

Claim to fame.

Max 05:43

Yeah, that’s the thing. Less abuse potential, potentially, you know, less addiction risk, things like that.

Alex 05:49

Can we, you said less, is it no abuse potential and no addiction risk?

Max 05:56

It’s a, it’s hard for me to always say something is yes or no and make it black and white, but I would say it’s pretty close to no.

Alex 06:01

Pretty close to no.

Nisha 06:03

That’s great. I’m excited. That’s what was related to the safety outcomes.

Alex 06:06

No data about safety outcomes.

Eric 06:07

So again, if people get bunionectomies for a short period of time, they’re not seeing a, are they seeing sedation? I know they’re not seeing opioid use disorder. I guess it’s not opioid use disorder cuz it’s not an opioid, right?

Alex 06:21

Right, right.

Alex McPherson 06:22

Addiction.

Nisha 06:22

Correct.

Alex 06:23

Yeah.

Nisha 06:24

Well, the other thing to note is that those pivotal trials only really used it for 48 hours. So they truly used it in the acute post-op period.

Alex 06:31

Yeah.

Nisha 06:32

And that was it.

Alex 06:33

Mm-hmm. So it’s like an early glimpse into this promising drug that maybe we should be excited about because this would be great if this did turn out to be helpful for our patients without potential for addiction.

Max 06:47

Yeah. In theory, it would be great.

Alex 06:50

Theoretically. Yes. Theoretically.

Eric 06:52

I mean, come on. This is a hot new drugs episode. Where is the excitement here?

Alex McPherson 06:56

We said, we said hot. We didn’t say effective. Okay.

Eric 07:00

So, okay, let’s talk about the efficacy.

Alex McPherson 07:02

Clarify.

Eric 07:03

What do we know about the efficacy of these drugs in the populations that’s studied? It, does it work better than opoids? If I’m remembering these trials right, it was compared to what? Hydrocodone?

Alex McPherson 07:18

Placebo, and then hydrocodone acetaminophen.

Eric 07:21

Does it work better than the opioid?

Alex McPherson 07:23

No.

Alex 07:24

No.

Eric 07:24

Does it work worse? We’re about the same.

Alex McPherson 07:28

It was not superior. It was not super correct.

Alex 07:31

Not yet.

Alex McPherson 07:31

And if you, and if you look at the endpoint that they use, so you need a PhD to understand it. I mean, and, and I do not have one. So it’s the SPID-48. So that stands for the summed pain intensity difference over this 48-hour time span. So I’m not going to explain the equation cuz it, you know, requires calculus and things, but They basically repeated, repeatedly measured pain scores for 48 hours and combined that improvement from baseline into one cumulative pain relief score.

And they found that suzetrogene, unsurprisingly, significantly outperformed placebo in both surgical models, but was not superior to hydrocodone acetaminophen.

Alex 08:19

Mm-hmm.

Max 08:20

Given every 6 hours for the hydrocodone acetaminophen, which is, you know, not ideal dosing for an opioid.

Alex 08:27

Yeah.

Max 08:27

So it’s really hard to, for at least for me to draw, you know, strict conclusions of this is a good drug. I mean, as far as the data goes too, they had a, a good amount of data imputation too. They were allowed rescue NSAIDs but didn’t really report NSAID use in their readily available data. So who knows?

Nisha 08:47

They are looking at, I skimmed the supplemental information and it did look, there was no statistical analysis on it, but it looked like it was about comparable how much ibuprofen they used in the hydrocodone group versus the suzatodrine group. But again, there’s no statistical analysis to actually confirm that it was the same or, right.

Alex McPherson 09:05

Right.

Eric 09:06

And they are looking at chronic pain though, right? They’re doing trials. Are those published yet?

Nisha 09:11

It’s not published yet. They’re looking specifically for peripheral neuropathy, and that’s because the specific sodium channel that suzatodrine

Nisha 09:23

Oh, right.

Max 09:24

There was a phase 2 trial that was a little bit earlier as well, looking at the lumbosacral one. Yeah. Painful lumbosacral radiculopathy. And they did not find a difference between placebo and suzetrogene. I mean, they did some, you know, post hoc analysis where they took out non-responding sites.

Nisha 09:41

Yeah.

Max 09:41

And they found that was significant. But when you look at the data pooled, there was no difference between placebo and suzetrogene.

Alex McPherson 09:46

Okay.

Nisha 09:46

So it’s Shoot.

Alex 09:46

not clear.

Alex McPherson 09:47

And, and even thinking about, you know, acute post-op pain, you know, nociceptive pain versus chronic neuropathic pain. I mean, biologically those are, are very different animals. So it’s not surprising, you know, and this like theoretic mechanistic plausibility obviously doesn’t, it doesn’t translate in this case to efficacy.

Eric 10:09

Yeah.

Alex 10:10

Have you heard of anyone using it in a palliative care setting already?

Alex McPherson 10:14

You know, I was shocked at AHPM when we were presenting our pre-con. I mean, we asked the same question and more hands than I thought, you know, would go up, went up. But in practice, I am not seeing it used a lot. Now, the caveat is that I’m mostly in an inpatient and outpatient palliative care setting

So if they’re using it in, you know, ortho, ambulatory care, post-op, I’m not. aware of that necessarily. I’m sure they are using it to some extent, but not in our patient population. I have not seen it being used.

Max 10:50

Anyone else? I’ve had one patient on it.

Alex 10:51

One patient?

Max 10:52

Yeah, I’ve had one patient. I, I mean, they were very hesitant to use opioids, had a lot of kind of idiosyncratic reactions to other non-opioid analgesics, and they use it with pretty good effect. I mean, there was a lot of limitations too for insurance because it’s only labeled for 14 days of use, so. It’s great if it works, but what do you do after those 14 days?

Alex 11:10

Oh yeah.

Alex McPherson 11:10

That’s a huge limitation.

Alex 11:12

What did they do?

Max 11:13

We did, I, I forget the exact specifics of, um, if we were able to get it like, you know, 14 days every month or what the stipulation was.

Alex McPherson 11:21

Or if you had to do some kind of prior auth, make a case. I don’t know.

Max 11:26

Yeah.

Eric 11:26

Nisha, have you seen it?

Nisha 11:28

I have not seen it in our palliative care population. Uh, where we work, I, uh, there is a pretty strict criteria for use of who can get it. And on the ortho side, there have been a lot of requests for it, but it’s only been approved twice. And in, in practice, it’s, it’s really hard to use it without the opioid. So what happened to both of those cases is that folks were using it just like another non-opioid adjunct, but then were also getting whatever their post-op opioid regimen would’ve been. And that’s very different than the way it was studied.

Alex 12:01

Yeah.

Nisha 12:02

We followed up on both of those cases and their opioid use didn’t seem significantly less than what you would expect.

Eric 12:09

And, and Max, you said it’s a sodium channel. Mm-hmm. And that, that’s different than like gabapentin, right? Gabapentin’s like sodium-gated calcium channel or something like that.

Max 12:21

Calcium channels.

Alex 12:22

Exactly.

Alex McPherson 12:22

Yeah.

Eric 12:22

So this is a different mechanism than gabapentin.

Alex McPherson 12:24

Different mechanism.

Eric 12:26

Yeah. But they’re trying to make it so everybody like gabapentin’s on it. Do we have it? Speaking of which, like 1 in 10 older adults are on gabapentin. Which is crazy.

Alex 12:34

Well, and I want to just emphasize, like, I’m going to be the optimist on this program because I feel like we want good options for our patients.

Alex McPherson 12:42

Yeah.

Alex 12:42

And boy, wouldn’t it be great if we had a non-addictive, you know, additional option for our patients for pain?

Eric 12:49

Yeah.

Alex 12:50

You know, even if it’s just some slice of our, the patient population that we’re seeing.

Eric 12:54

But the fascinating thing is if, if you did a trial of hydrocodone, which this, this did, is that you wouldn’t see those safety issues in a 48-hour trial of hydrocodone. Probably you’d have to follow them for a long period of time. And I’m guessing very few older adults were in the bunionectomy.

Alex McPherson 13:14

The average age, do you remember, guys? It was like 40s or something. I mean, it was certainly not, not our patients.

Nisha 13:22

And I think the most age wasn’t very old either.

Max 13:24

No. And these are mostly our cosmetic surgeries, a tummy tuck and a bunionectomy. So I think it’s usually a, Younger population.

Eric 13:32

All right. And it’s very expensive, right?

Nisha 13:35

Yes. Do either of you know if there are coupons out if folks don’t get it covered by insurance?

Max 13:40

Yeah, I think through Vertex there are some patient assistance programs.

Nisha 13:43

Okay.

Eric 13:44

Okay. Let’s imagine it was not very expensive. Do you see with the current evidence that, that you have, do you see particular patients in the palliative care world or in the geriatrics world Where you would say, huh, let’s do this hot new drug. Max, I’m going to start off with you.

Max 14:03

Potentially. I mean, there’s always those people that just don’t tolerate other—

Eric 14:07

Yeah, you had one on it, right?

Max 14:09

Exactly. So there’s always going to be that, that person who doesn’t tolerate any.

Eric 14:12

But this is not going to be your first go-to drug, even if it was the same cost.

Max 14:16

Probably not. I mean, you know how I feel about buprenorphine and that I’m on that train.

Alex McPherson 14:22

Your first love.

Max 14:23

Exactly.

Eric 14:24

Alex?

Alex McPherson 14:26

Yeah, I agree. I mean, I think where I see it and where I think a mistake may have been made in kind of marketing this product is, you know, it was kind of sold as this novel non-opioid analgesic, kind of comparing it to opioids, but it is not a replacement for opioids. So I think as part of a multimodal regimen, could it play a role? Sure. Is it going to replace the drugs that we’re currently using? No. But, you know, acute post-op pain, acute, you know, in our patients, pathologic fractures, post-op cancer pain.

Eric 15:05

Yeah.

Alex McPherson 15:06

Some invasive procedure, like acute, trying to think, radiation-associated pain. Like Max said, opioid intolerances, severe opioid-induced constipation, opioid use disorder, some sort of significant respiratory vulnerability.

Eric 15:22

And it doesn’t, as far as we know, no constipation with this drug, no sedation as far as we know. Again, they didn’t include older adults, but no, I don’t think so.

Alex McPherson 15:32

Not like opioids.

Eric 15:33

And healthy 40-year-old women with bunionectomies.

Alex McPherson 15:36

Correct.

Alex 15:37

Well tolerated.

Eric 15:37

So these are—

Alex McPherson 15:38

slam dunk. Yeah.

Eric 15:39

Is there a role here?

Nisha 15:41

I, there’s a potential role there. I, I agree with Max and Alex. I think it’s gonna, it’s not gonna be my go-to. It’s definitely not gonna be a replacement for any of the meds that we currently have. It’d be nice to have an adjunct, and I just, I wanna see more, like you said, safety data.

Alex 15:57

Right.

Nisha 15:58

Because our patient population’s just so much more vulnerable and it makes me nervous to try a medicine where I don’t know what the effects are gonna be beyond 14 days.

Alex McPherson 16:07

Yeah. The other thing, just briefly too, is the, like how fast it works, right? Which It’s not very, so I, I think it’s like on the order of hours. So, you know, in terms of timing, so if you have a patient with, you know, rapidly escalating pain or even acutely post-op, you’re gonna want something that works like, you know, 10 minutes ago, not hours from now.

Nisha 16:33

Yeah.

Alex McPherson 16:33

So am I going to be reaching for this or the IV hydromorphone that we know works in, you know, 5 to 15 minutes? Definitely, I’m going to be picking the latter. So does it have a potential place? Maybe, but I think there are a lot of patients in our population where there are better options.

Eric 16:53

Yeah. So maybe if you have a hospice patient who’s getting a bunionectomy.

Nisha 16:59

There you go. Yeah.

Alex McPherson 17:00

Sign ’em up.

Alex 17:01

You’re the pessimist.

Eric 17:04

I’m seeing a largely you know, not ready for prime time on this, but hopeful we’ll get better data in the future. Max, you were telling me earlier about a hot new drug that is actually an old newish.

Alex 17:20

Yeah.

Alex McPherson 17:20

Newish.

Max 17:21

Yeah.

Eric 17:22

What drug is that?

Max 17:23

Yeah. Levophed. So if you, I mean, if you consider 1950s new, then you’re, you’re spot on with it. I mean, my argument is it’s, it’s a great drug. From a theoretical standpoint.

Eric 17:34

So it’s weird, I don’t see any drug ads for levophenol when I’m watching NPR or PBS. That’s the problem. Yeah.

Alex McPherson 17:42

We need the drug ads. We need the drug ads.

Eric 17:45

What is levophenol?

Max 17:47

Yeah, so it’s a phenanthrene opioid, so it’s got your opioid effects, SNRI effects, and very strong NMDA antagonism. So I know we’re often thinking, thinking about things like Methadone is kind of analogous where you have the opioid effect, SNRI effect, and then probably pretty weak, uh, it does have pretty weak NMDA antagonism effect, but levorphanol is even on par with like ketamine as far as the NMDA antagonism goes. So great drug for mixed pain signals, both neuropathic, nociceptive. And the, the beauty of it in comparison to methadone is it doesn’t cause QT prolongation.

Eric 18:22

Oh really? Yes.

Nisha 18:24

Yep.

Alex McPherson 18:24

So, and, and way less drug interactions.

Eric 18:27

Get outta here.

Max 18:28

Yeah.

Alex McPherson 18:29

It’s, it’s methadone without the drama. It’s like the Swiss Army knife.

Alex 18:33

Yeah.

Max 18:35

So I think it really needs a renaissance.

Nisha 18:37

It does.

Max 18:37

Period.

Alex McPherson 18:38

So if only it wasn’t so expensive.

Eric 18:41

Oh, it’s expensive. It’s an old drug. Why is it so expensive?

Alex McPherson 18:44

Because no, no one is prescribing it. No one’s using it. I, I was pulling up data before this just to see like, is this on any insurance formularies? Like, is this even possible to get. And it said, I think it was looking at, see if I still have it, like Medicare Advantage plans. And I think it said like 2 to 3% of plans cover levophedanol.

Alex 19:08

Oh wow.

Alex McPherson 19:09

Something like that. So it’s, it’s there, but hardly any plans cover it. I would be willing to bet that most pharmacies do not stock it.

Alex 19:19

Oh.

Alex McPherson 19:19

It’s expensive. It was. I don’t know how long ago it was rebranded. The generic was rebranded under Zyvana. Is that the name, Max? Zyvana?

Max 19:28

I think that’s right.

Alex 19:28

Yeah.

Alex McPherson 19:29

Yeah. So it’s just really expensive from, I looked it up on Lexi. It said 2 milligram tablets anywhere from $40 to $53, 3 milligram tablets, $80 per tab.

Eric 19:42

So, $80 per tablet.

Speaker 5 19:44

Whoa.

Alex 19:44

Yeah.

Alex McPherson 19:45

Nothing to, to sneeze at.

Max 19:47

So when we’re talking expensive, it’s not hundreds of dollars, it’s thousands of dollars a month.

Alex McPherson 19:50

Yes. Yes.

Eric 19:51

Have you seen it used at all?

Max 19:54

Once.

Eric 19:55

Once?

Speaker 5 19:56

Yeah.

Max 19:56

It was a guy that we had to switch off of methadone because of QT prolongation and drug interactions. And we’ve tried every other full agonist opioid. It was, it didn’t tolerate or no efficacy. So we did switch to levophedanol. And it was, if I’m remembering right, if you do like a membership program for one of the discount cards out there, it was about $300 to $400 a month. So still very, very, very expensive.

Eric 20:24

Wow.

Alex McPherson 20:25

Less than the $20 grand, I guess, without, yeah, without the assistance. But still, I mean, for most patients, prohibitive. For all hospices, prohibitive.

Nisha 20:35

Yeah.

Alex McPherson 20:36

So yeah.

Eric 20:38

Oh. Dang, we are striking out a little bit.

Alex 20:40

Well, it’s potential, but we—

Alex McPherson 20:41

We want to use it though. Unlike the other one, we, we want to use it.

Eric 20:46

Can I ask?

Nisha 20:46

I’ve got a little bit of a different perspective here, um, because I, I read all of that data and it sounds really promising. And I think I agree with you all. The barrier to actually like seeing it in practice is the cost of it. Um, where I work, when we sit on— we sat on a P&T committee and we were thinking about, are we gonna add this to our formulary? Are we gonna be using this? And the thing that kept coming up is a lot of the data, the people who were involved in publishing that data just had a lot of conflicts of interest that they didn’t disclose.

Eric 21:19

‘Cause it was 1950?

Nisha 21:21

Well, no, when they re— I can’t even remember.

Alex 21:22

When they rebranded it.

Max 21:24

Early 2000s.

Nisha 21:26

Yeah. And so that actually, and it, that was when I was talking to some colleagues who work at other places. that tended to be kind of the reason that a lot of P&T committees, um, insurance companies wouldn’t actually take it. So there’s, I don’t know how much I believe that that is a component of it.

Alex 21:43

Yeah.

Nisha 21:43

It’s just, um, I think for folks who, when you read the data, it looks really promising. And because we have this barrier preventing us from actually using it, we can’t definitively say that it is promising. And then a lot of this data is clouded. Mm-hmm.

Eric 21:59

Yeah, that’s a great point, especially early 2000s. That’s pre-open payments. Like you don’t know who’s getting what and how people are being supported. Is it the same? So we’ve talked about some of the issues with methadone that it may be better with. So more pure NMDA, less drug-drug interactions, no QTc prolongation.

But what about like dosing issues? Because the other challenge with methadone is You gotta actually know how to dose it, how frequently to change it, how to switch somebody from their current opioid to methadone is not as clear and as, as other drugs. Same thing with this drug.

Alex McPherson 22:40

Kind of. Akila Reddy published a really nice paper. I think it was, it was early, maybe 2020 or so, that helped with the conversion. So showing anywhere from like 12 to 25 or so to 1 with the conversions. But the same issues as with methadone apply, right? The, the lack of familiarity with the medication kind of itself. Add to that the difficulty with conversion. It, it makes it challenging. Not to mention all the logistical, you know, kind of barriers that we just mentioned.

Alex 23:17

Yeah.

Max 23:17

And it’s pretty similar to methadone too, in the way that it’s not inherently super long-acting, but with repeated doses it has a long terminal Yeah. So that makes it kind of hard with switching because you’re gonna have that taper-up effect like you do with methadone as well.

Eric 23:31

Yeah.

Max 23:31

And like Alex was saying, there’s, there’s like package insert dosing versus like what Akhila Reddy put out and other groups put out. There’s some even suggest it has like that sliding scale kind of conversion ratios that like methadone has to, like depending on how many OMEs you’re converting from, you might have more or less ratio.

Eric 23:49

But that said, you always either get 5 TID or 10 TID with methadone.

Alex 23:53

So I’m not sure why we, I thought it was 5 or 15. No, 5 or 10.

Max 23:58

Yeah.

Eric 23:58

15 always goes like you have to then break it in 3 times a day.

Alex 24:01

Oh, okay.

Nisha 24:02

Yeah.

Max 24:03

Okay.

Eric 24:04

So I’m, I’m guessing on this one would be great if it was cheaper, very limited access, maybe as a backup to a backup. If you can get it, it may be helpful for particular patients.

Alex 24:19

And maybe, and we need more current Studies in our population.

Alex McPherson 24:23

Yeah. For sure. I think the, the lack of evidence is, it’s in addition to all the other stuff is kind of its Achilles heel that the evidence base is just very thin.

Speaker 5 24:33

Yeah.

Nisha 24:33

And there’s just no incentive to study it either.

Alex McPherson 24:36

Right, exactly. I think Akila Reddy had wanted to continue studying it and I think the drug company wouldn’t provide additional drug. Like it wasn’t for lack of trying. So the, the need is there. The desire is there.

Eric 24:52

Methadone’s been out since 1940 and yet we still have studies on that.

Alex McPherson 24:57

I know. What the heck?

Nisha 24:58

Yeah.

Eric 24:59

Oh yeah.

Max 25:00

It’s unfortunate.

Alex McPherson 25:01

It’s also a lot cheaper.

Max 25:02

Yeah.

Alex 25:03

A lot cheaper.

Alex McPherson 25:03

A lot cheaper. All right.

Eric 25:04

Let me ask you about another one. Uh, is it tapentadol?

Nisha 25:09

Yep.

Alex McPherson 25:10

Yep.

Nisha 25:10

Tapentadol.

Eric 25:12

Can I ask a separate question? How annoyed are pharmacists when physicians try to pronounce these names and just butcher them?

Alex McPherson 25:22

I think we’re used to it by now.

Alex 25:24

All right.

Eric 25:25

Don’t ask me how I’d spell these, by the way. Okay. What is it? How’s it called, Nisha? What’s it called?

Nisha 25:31

Topentadol. That’s how I say it.

Alex McPherson 25:33

Yeah.

Eric 25:34

What is this drug?

Nisha 25:36

So this is also a drug that’s ancient, been around for decades now. And just has never really been come to like use in practice. I think of it as kind of a reformed tramadol. And so it is.

Speaker 5 25:52

Uh-oh.

Alex McPherson 25:52

Uh-oh.

Nisha 25:53

I know.

Alex McPherson 25:54

What do you think about people calling it strong tramadol?

Eric 25:57

Strong.

Alex McPherson 25:57

‘Cause I hear that sometimes.

Nisha 25:59

I just roll my eyes.

Eric 26:01

I’m gonna refer for all of our listeners who have not listened to the David, David Jurlink episode on Tramadone. Highly encourage you to go to that episode. Check out, uh, we’ll have a link to it on our show notes. But basically, I think he, if I remember, he had a beautiful quote about it. It’s like if a, I won’t even remember the quote, but I do remember him saying it’s like a really bad opioid mixed with a really bad SSRI.

Alex 26:24

Yeah. An unknown quantity.

Eric 26:25

An unknown quantity. And that’s what you’re giving when you’re giving tramadol.

Alex 26:29

Yeah.

Alex McPherson 26:29

So this is the better, is this tapentadol? Is that what we’re saying?

Eric 26:34

Nisha, what is this?

Alex 26:35

Oh, you think so? I don’t.

Eric 26:38

Oh, fun. We got disagreement. Nisha, tell me why. First, tell me how it works. Pharmacology.

Nisha 26:46

So it is, so it is a mu agonist just like other opioids. It is a, it is a little bit more potent than tramadol. We’re looking at, and the data showed about 2 to 3 times more potent than tramadol. And then they also had some data that compare it to morphine. It’s about 2 to 3 times less potent than morphine.

So we’re seeing somewhere in between there. And then the difference between tapentadol and tramadol is tramadol has both serotonergic and norepinephrine kind of targeted effect. So more of the SNRI type effect with the mu. Did I say tra— that was tramadol. Tapentadol does not have the serotonergic effect as much, but does have the norepinephrine effect. So we are taking off one type of receptor activity compared to tramadol.

Eric 27:30

But no risk for serotonin syndrome like you see with tramadol.

Nisha 27:34

Like Max said at the beginning, I hate to say no risk.

Alex 27:39

Less risk.

Nisha 27:40

In theory, less risk. I still say it’s a don’t. I don’t think of it as a, as strong a don’t as tramadol, but I think it’s a don’t because given all the other options we have, I can’t see making a case for it. It’s really expensive. It’s not as well studied. And I would rather just use an opioid that’s true and tried and not having any other kind of receptor activity unless I intend it like methadone and I want the NMDA activity.

Alex McPherson 28:09

Right.

Alex 28:10

Yeah.

Eric 28:11

So you can always combine morphine with an SSRI or SNRI.

Nisha 28:16

Totally.

Alex 28:17

Right.

Eric 28:17

Get that. Oh, hey, Max. Yeah. Max, come on.

Max 28:20

You said the voice is in here.

Alex 28:23

Yeah.

Eric 28:23

Topentadine.

Max 28:25

Topentadine. Uh, yeah. Topentadine or Topentigo.

Alex McPherson 28:28

I mean.

Max 28:29

The huge benefit it has over tramadol is it doesn’t require enzymatic activation. So the tramadol, tramadol itself is that more of that serotonergic reuptake inhibitor, then it gets converted into that opioid. Tapentadol doesn’t require that enzymatic activation. So from a reliability standpoint, it’s much, much better than tramadol.

Eric 28:49

So it fixes that one issue that—

Alex McPherson 28:50

Like interpatient pharmacogenomic variability.

Max 28:54

Exactly.

Eric 28:54

So it fixes that one issue that Alex brought up. We don’t know with tramadol what quantity we’re giving them because it really depends on metabolism. Metabolism.

Max 29:05

Exactly.

Alex McPherson 29:05

Correct.

Eric 29:06

And this, you don’t have to worry about that. Yeah.

Max 29:09

I mean, I think there is a role for tapentadol though. So thinking for people who have especially like centrally mediated pain pathways, whether it be hyperalgesia caused from just chronic pain, opioids, fibromyalgia type pain. Where you’re, you know, you still have a reason for pain in the periphery, but there’s that whole descending pain pathway that you can target with tapentadol and it does a pretty good job with it.

I mean, anecdotally, we’ve used it for a decent amount of patients, both the ER formulations and IR formulations, and I’ve had very good success for it, especially when we are like the, the patients I’m thinking about, they’re going, they have cancer, but they also have underlying fibromyalgia or some other kind of central pain pathway and it works phenomenally well for them.

Alex 29:50

Oh, wow. Is it affordable for your patients? Do you have a, They, they tend to be able to, it’s not an issue. It’s not like they’re paying thousands and thousands a month for this.

Max 29:58

Like with everything in the world, it requires a prior authorization. But if you have, I think, good evidence, like saying like, we tried these medications, we tried other things.

Alex 30:07

Yep.

Max 30:07

I haven’t had too bad of luck getting it covered.

Alex 30:11

So you would probably have to try, as Nisha said, other meds first before you got to this one.

Alex McPherson 30:16

Yeah.

Alex 30:17

Yeah.

Max 30:17

I mean, like especially government-funded insurances, you’re probably going to have to try 3 others before you get to tapentadol. But commercial insurances, you might, your mileage might vary a little bit.

Eric 30:26

All right, we got 1 for, 1 against. Alex, you’re gonna be our tiebreaker.

Alex McPherson 30:31

I’m in the middle. Oh, I’m in the middle. So, you know, I think as compared to, you know, some of the others we’ve talked about, you know, we’re not with tapentadol, we’re not really looking for proof that it works. We know it works, but What I am less convinced about is whether that kind of dual mechanism in one creates like enough of a real-world advantage over a really inexpensive opioid plus an adjuvant.

Eric 31:00

Yeah.

Alex McPherson 31:01

To justify, you know, the cost and complexity associated with it. But I mean, if you have a re— like, I, I just had a patient the other day, you know, in prepping for this and I was like, man, this, this probably would’ve been a good option. Where the patient didn’t tolerate gabapentin or pregabalin. They had these horrible tremors. When we stopped the gabapentin, they went away entirely after a few days.

So I was like, okay, well, I guess it was that. Couldn’t tolerate duloxetine due to nausea, vomiting. From cardiac standpoint, we couldn’t do a TCA. They needed that opioid analgesic pathway. So, you know, in, in cases like that where you sort of are out of options. And you can benefit from this dual mechanism. I think it has a role. Is it, is it my go-to? Is it my like first or second choice? No.

Eric 31:51

Would you choose it over tramadol?

Alex McPherson 31:53

100%.

Alex 31:54

100%. All day. Everybody’s agree—

Max 31:57

everybody agrees about that.

Alex McPherson 31:58

Yeah.

Eric 31:58

Choose it over tramadol.

Alex 31:59

But that’s a low bar.

Eric 32:01

Well, what is the, is it a lot more? Do we know if it’s more expensive than tramadol?

Nisha 32:05

Oh yes.

Alex McPherson 32:06

Yeah.

Nisha 32:07

Yeah. I have a follow-up question for Alex and Max. In those situations, I usually reach for bup. I heard earlier, Max, that’s one of your go-tos as well.

Eric 32:17

Buprenorphine.

Nisha 32:18

Yeah. Oh, buprenorphine. Sorry, I didn’t mean to give anything.

Eric 32:21

Inside.

Max 32:22

Yeah, I just wanna, I mean, I am a huge bup advocate, buprenorphine advocate. I will say if you have someone who clearly does have a mixed nociceptive neuropathic pain pathway, I would I would say that tramadol or tapentadol would be a, a better choice. Like buprenorphine does have some, I would say soft neuropathic benefit.

It has some sodium channel blockade, which may or may not contribute to its total pain picture or analgesic picture. But for those cases where I suspect central sensitization and a very strong neuropathic component, I think maybe tapentadol would have edged it out. But Usually for me, buprenorphine’s gonna be the go-to.

Eric 33:03

And for our listeners, we’ll have links to the buprenorphine podcast that we’ve had. But real quickly, Max, if you’re gonna start somebody on buprenorphine, like for this patient that you’re, you’re thinking about these, like tapentadol, tapentadol, which, which formulation of buprenorphine would you be thinking about?

Max 33:22

I mean, it really depends on patient-specific kind of scenario. Like, is there any history of opioid use disorder?

Eric 33:28

Yeah.

Max 33:28

Or if we’re just using this purely for pain and they have relatively—

Eric 33:31

Purely for pain.

Max 33:32

Purely for pain, low kind of OME requirements, it’d be the transdermal patch.

Eric 33:37

Transdermal patch, start at 5 micrograms per hour, which is like what, 10 or 12 milligrams of morphine a day?

Nisha 33:43

Yeah.

Eric 33:44

Okay. Okay. Next, next group. Are we okay moving to the next?

Alex McPherson 33:50

Yeah, let’s do it.

Eric 33:52

Dora’s, what, what is a Dora?

Alex 33:55

The Explorer.

Eric 33:55

Not an explorer.

Alex McPherson 33:57

That’s what I think of every time is the little girl in her backpack.

Alex 34:01

That’s right.

Eric 34:02

We are not. What is it? What is a DORA and why is it useful potentially in palliative care?

Alex McPherson 34:07

So DORAs are dual orexin receptor antagonists. I believe there’s 3 on the market right now. The brand names are Belsamra, Dayvigo, and Qvivic. And basically they, they kind of block the wake-promoting systems. So in kind of fundamentally different from Like the benzodiazepines and the Z drugs.

So, you know, our traditional hypnotics like the benzos and the Z drugs basically kind of sedate the patient, push the brakes. So this is kind of like taking the foot off the accelerator. So kind of the best, the best way that I’ve wrapped my head around it.

Eric 34:50

Do they work?

Alex McPherson 34:52

Yeah, they do.

Nisha 34:52

They do.

Alex McPherson 34:53

They do work.

Eric 34:54

Is it like they, like, like the Z drugs work where they gives you like, you know, you go to sleep 10 minutes, maybe a little faster, but then it kind of messes up your, your sleep architecture? Or is it like, what do we know about how effective they are?

Nisha 35:11

So the data that initially got them published actually advertised that it does not mess up sleep architecture.

Alex 35:19

All right.

Nisha 35:20

And it’s focus is on sleep maintenance. And when you think about the mechanism that Alex just went over, that makes sense, right? ‘Cause we’re not just, um, we are trying to take our foot off the accelerator as opposed to just being like, let’s snow you.

Alex McPherson 35:33

Knock ’em out. Yeah.

Nisha 35:35

Yeah. I will say, I’m, I’m actually curious if either of you’ve had a lot of experience using it. I have only had one patient on it ever, and my major complaint is similar to my complaints with every other drug. is I think it has really great potential, but because it’s expensive, it’s formulary restricted. And so you have to try the benzos and the Z-drugs, which are usually on formulary.

Alex McPherson 35:59

Which we’re trying to avoid at all costs in most of our older patients.

Nisha 36:04

Exactly. But I actually think in this case, the Doras would be the safer option and actually could be the first-line option, especially in the era where we’re seeing a bunch of new data. telling us that mirtazapine and trazodone are really not gonna be helping us with folks who have insomnia.

Max 36:21

Yeah, we use it not infrequently. I mean, there’s a lot of benefits and there’s even trials suggesting they’re more efficacious than C-hypnotics, melatonin. They don’t have that abuse potential as well. So we do use it pretty frequently.

Eric 36:36

Do you get that drowsiness with them?

Max 36:37

You can still get, yeah, that’s the main kind of side effect. I mean, they all differ in kind of their onsets of action, times to peak and things like that, but they’re all, they’re all pretty good.

And I’ve had very good success with using them, especially in populations where we’re worried about anticholinergic burden, we’re worried about the hypnotics. I think it’s a great option for many folks, and especially with the improved efficacy over a lot of the traditional things that we use, I think it’s a great, great option.

Alex 37:02

When, when you said the, the, was it dual orexin? What is it?

Eric 37:07

Orexin.

Alex 37:07

Orexin. Isn’t that an antiemetic that is also in that class, or am I misremembering? No, no. I don’t know why I’ve heard that before. I thought it was an antiemetic. Okay. Not ringing a bell. Made that up.

Alex McPherson 37:20

Trying to think what, what would it be?

Eric 37:21

We did do a podcast on sleep and we talked about the DORA, so we’ll have another link to that in our show notes.

Alex 37:27

And, and are any of these coming off, like, uh, they, will they be generic and is there a potential for them to be more affordable in the near future? Anybody know? Have they been around for a while? Are these all pretty new to market?

Max 37:38

They’re pretty new within the last 10 years. I, I don’t know when their patent exclusivity runs out. Yeah. So I mean, they will go generic at some point. I don’t know the exact timeline though.

Alex 37:46

Yeah. Okay.

Alex McPherson 37:47

Yeah, I’ve gotten them covered. I mean, hoops have had to be jumped through, but it’s not as prohibitive as, you know, some of the others that we’ve mentioned, but they’re definitely not just Covering them without proving that you’ve tried other things.

Nisha 38:04

Yeah, I think I’ve been able to get it approved if folks, uh, if I can make a strong case that Z-drugs and benzos are absolute no-nos, but generally to be able to even get a trial, I have to do a small trial of a Z-drug or a benzo.

Speaker 5 38:20

Oh, really?

Eric 38:20

Even in an older adult?

Nisha 38:22

Even in an older adult. Do you have to make me do this?

Alex McPherson 38:24

I’m like, please don’t make me do this.

Eric 38:25

Please. They, do they make you prescribe trazodone? The, the drug that has very little evidence, but we use it all the time.

Alex McPherson 38:33

In everyone. Everyone. Trazodone for all.

Eric 38:37

And mirtazapine.

Alex McPherson 38:37

Yeah. The other bane of my existence. The one thing that gets interesting with these DORAs is the question of delirium. So we know that sleep disruption and delirium kind of reinforce each other. And we also know that our traditional sedatives worsen the risk of delirium.

So with that, the researchers of these DORAs kind of posed this very nice hypothesis that was, if we normalize sleep-wake signaling instead of broadly sedating the brain, could we prevent delirium? So there was a phase 3 trial. It was like, I don’t know, a little over 200 hospitalized adults at an elevated risk of delirium. And they found that delirium occurred in 17% in the DORA group and 26% in the placebo group. So that looks exciting. Exciting, right? It wasn’t statistically significant.

Eric 39:37

Okay.

Alex McPherson 39:38

Small study.

Alex 39:39

Yeah. Yeah.

Alex McPherson 39:40

Right. So, you know, you said you got struck here.

Eric 39:42

We’ll include it in our show notes so the readers know.

Alex 39:44

That is really exciting. Boy, this is the optimism.

Eric 39:48

Yeah.

Alex McPherson 39:48

Right. So numerically lower incidence, right? Um, didn’t reach statistical significance, but It’s hypothesis generating, right?

Max 39:56

Mm-hmm.

Alex McPherson 39:56

So it’s, it’s intriguing. It’s not necessarily practice-changing proof, but yeah, there’s a 2026 systematic review kind of like looking at all of this. And I think a study ongoing now that’s like sort of directly examining, I think it’s comparative falls, delirium outcomes, and maybe something else against benzos and the Z-drugs in older adults with dementia.

Alex 40:22

Oh.

Alex McPherson 40:22

So basically you’re just showing how actively this is sort of evolving some of the questions involving these drugs. So it’ll be interesting to see the data once that comes out because that is one of a huge role that these could play.

Alex 40:39

Yeah.

Alex McPherson 40:40

In insomnia in our older adults.

Eric 40:43

Except if there’s still some daytime sleepiness, that should make us concerned unless we have really good evidence in older adults.

Alex McPherson 40:50

Exactly.

Eric 40:51

Okay, anything else on Doras before we move on to our last one? All right, hot new drug for everything.

Alex 40:59

Everything works for everything. Dementia right away.

Eric 41:02

Azepic, right? Wegovy.

Alex McPherson 41:06

Put it in the water.

Eric 41:07

Is there a role for these drugs in palliative care? Because people are saying it does everything. Nisha.

Nisha 41:16

All right. I’m going to, I’m going to start by saying, I, I really, really hate that they’re just putting GLP-1s on everything. But the reason I wanted to talk about this is in our outpatient clinic, we’ve gotten several consults for appetite, for poor appetite, asking us to start some pharmacologic therapy for folks, for folks who have advanced cancer, are losing weight rapidly, and have—

Alex McPherson 41:41

I see where this is going.

Nisha 41:43

And they come to our clinic and we do our intake and our thorough med rec, and lo and behold, they are on a GLP-1. And my advice is always, but Nisha, they look great.

Alex McPherson 41:56

It’s just, sometimes they’re already on both when they come to us and I’m like, yeah, make it make sense.

Eric 42:04

They’re, they’re on both an appetite stimulant and an appetite suppressant.

Alex 42:09

And it’s, yeah.

Nisha 42:10

And I’m like, and it is my pet peeve. I’m, and I always send it back saying, but, but change for the, the GLP-1 first.

Alex 42:19

But we fought so hard to get on it.

Nisha 42:21

Yeah.

Alex 42:22

Right. It was such a battle to get approved and get on it. And now you’re saying come off of it.

Eric 42:27

And every day I open the news, GLP-1s prevent dementia. They help with opioid use disorder. They’ll get you stopped smoking.

Alex 42:35

Metabolic disorder. Yeah.

Eric 42:35

They will improve your marriage. They will make you money.

Nisha 42:42

And that is the challenge we’re facing.

Alex McPherson 42:43

Yeah.

Nisha 42:44

Really, really don’t want to let go of their GLP-1s. Um, and because they had to fight so hard to get on them, um, when the clinical picture changes and the benefits are no longer outweighing the risks, it is so hard to help them see that, visualize that. And it’s not just, um, our patients. It’s also their other team, their clinical team members, like their primary care team, primary who we—

Alex McPherson 43:11

The heart, the advanced heart failure team. Yeah. The nephrology team. Everyone that loves the GLPs.

Alex 43:17

Yeah.

Alex McPherson 43:18

Yeah. And it’s funny, if you look at the 2026 American Diabetes Association guidance, like usually these associations take, you know, a pretty hard stance on certain things, but their guidance is, is remarkably kind of palliative-friendly, generous.

Like it says it’s not preferred in older adults with unexplained weight loss, undernutrition, problematic constipation, significant gastroparesis, recurrent ileus, and bowel obstruction. Not preferred.

Eric 43:51

Like contraindicated. I’m going to also encourage all of our listeners. We just did a podcast on GLP-1s about how really my take from that one is you have to have good nutrition and advice on that, and you have to be able to exercise before you can start a GLP-1. So encourage you to check out. But Max, yes, I’m going to go over to you. But is there a role specifically for initiating a GLP-1 in palliative care?

Max 44:19

Maybe not. It’s hard to say. I have a bias because most of my outpatient work’s in a palliative care harm reduction clinic where we have people who are struggling with Yeah. Serious illness, but also substance use disorder. And I think from the angle of substance use disorder, alcohol use, opioid use, I think we’re gonna get more and more data looking at if they can help reduce relapses or reduce use.

Because we know with people with serious illness, especially cancer, they’re at an elevated risk for developing a substance use disorder, especially opioid use disorder.

Alex 44:50

Yeah.

Max 44:50

So I think there can be a specific role for very niche populations, but Blanket statement. I, I agree with like what Neisha was saying. All of our patients are, a lot of our patients already kick out.

Alex McPherson 45:00

Yeah.

Max 45:00

We’re worried about muscle mass, nutrition. So for those folks, no. But for some select people, maybe.

Eric 45:07

Max, where, where do you think we are? ‘Cause like for the dementia, the GLP-1s and dementia, like there was a TARGET trial emulation study that came out that got a lot of news, which was horrendous. Like it, it decreased dementia risk on day 1 of being prescribed the drug. I think actually before you were actually prescribed, like you were prescribing the drug.

Alex McPherson 45:25

When you just thought about it. Yeah.

Eric 45:26

Just thought about it, your dementia risk. And then cancer, same thing. Like you just think about it and your cancer risk decreases, which is the biggest issue is that there’s a ton of confounding. Is it the same thing? And interestingly enough, for the dementia one, when you actually did a randomized controlled trial, it actually did not show any benefit with improving or maintaining brain health. Where are we with addiction? Do you know?

Max 45:51

Like we know, I mean, the science kind of backs it. We know that it works in the reward pathway within the ventral tegmental area, nucleus accumbens. So that’s the same pathway where you get those dopamine releases and addiction forms with other dopamine-releasing drugs. So there, I mean, I think the most of the studies that I’ve looked at recently have been alcohol use, but I know there are some in—

Eric 46:12

But they’re all retrospective cohort.

Max 46:14

Exactly. But there, I mean, there are prospective trials now looking at opioid use disorder. They’re not completed yet, but yeah, I’m gonna be very interested to see what their results are.

Eric 46:23

Mm-hmm. ‘Cause I mean, I think the biggest issues, I’m optimistic, the, the people who could get Wegovy or Ozempic, yeah, a year or two ago were a very different population than people that weren’t.

Nisha 46:35

Yeah.

Eric 46:35

That’s wonderful. I think we hit all of ’em.

Alex 46:37

Yeah. Nice. You gonna ask your, oh yeah, you said at the beginning you were gonna ask a last question. Real quick lightning.

Max 46:43

Lightning.

Eric 46:43

Keep it short. Make the case why every palliative care team should have a palliative care pharmacist. Max, start off with you.

Max 46:53

We’re fun. I think we’re, we, there’s so much gray zone in palliative care and, you know, tying the theoretical to the symptom and the patient that you see in front of you. And I think palliative care pharmacists can really help with that link between the theoretical data and the patient that’s in front of you. So I think they’re the best.

Eric 47:10

I agree. Alex?

Alex McPherson 47:12

I agree. We are obviously the most fun discipline on the team, but also we’re the only clinicians really trained to, trained to manage the complexity, you know, the, the interactions, the conversions, the deprescribing, all of which, you know, share the goal of keeping the patient safe. So we prevent harm, we optimize comfort, and hopefully help, you know, make the entire team better.

Eric 47:38

Lovely. And Nisha, before I, I just wanna say one thing. I didn’t know why we needed a palliative care pharmacist until Nisha joined our team. And now I can’t imagine not having a palliative care pharmacist. Nisha, what’s your, what’s your lightning?

Nisha 47:52

Everything that Max and Alex said. And the other thing I will say is pharmacists who do a postgraduate training, so any kind of residency, we, our palliative care training is actually baked into pain management. and substance use disorder, which is a different perspective than the medical training that usually comes from the geriatric lens. And so I think that combination is what really helps us serve our very diverse population. Awesome.

Eric 48:19

Well, let’s hear a little bit more of Kesha, Keisha, Kesha.

Alex 48:22

Kesha. Get it right.

Alex 48:28

(singing) “Maybe I need some rehab or maybe I just need some sleep. I got a sick obsession. I’m seeing it in my dreams. I’m looking down every alley. I’m making us desperate calls. I’m staying up all night hoping, hitting my head against the wall. What you got, boy, is hard to find. I think about it all the time. I’m all strung out, my heart is fried. I just can’t get you off my mind because your love, your love, your love is my drug. Your love, your love, your love. I said your love, your love, your love is my drug. Your love, your love, your love.”

Eric 49:24

Max, Alex, Nisha, thanks for joining us on this podcast.

Max 49:27

Thanks for having us.

Alex McPherson 49:28

Yeah, thanks for having us. It’s been fun.

Eric 49:31

And thank you to all of our guests for your continued support.

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