Suzetrigine

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DoYouEvenLiftBro

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pubmed.ncbi.nlm.nih.gov

Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain - PubMed

The comprehensive pharmacology assessment presented here indicates that suzetrigine represents the first in a new class of non-opioid analgesics that are selective Na<sub>V</sub>1.8 pain signal inhibitors acting in the peripheral nervous system to safely treat pain without addictive potential.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

potential new drug / receptor for pain

NaV1.8 receptor, peripherally/DRG C fibers
Suzetrigine multiple phase 3s, company Vertex
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yeah looks like just acute pain, all the studies were post surgery, trauma or accident. Looks like they’re looking into chronic use. Approved after hours
 
i knew someone was going to post on this. moderate acute pain.


it is another NaV (sodium channel) agent. as is lidocaine. its claim to fame is its selectiveness to peripheral nociceptors.


apparently there are 2 studies out there, none of which appear on pubmed. neither did anything show up on medrxiv.

one for abdominoplasty, one for bunionectomy, and compared to placebo and patients faired better (this is per the FDA release).

here is the safety study done:

pubmed.ncbi.nlm.nih.gov

Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain - PubMed

The comprehensive pharmacology assessment presented here indicates that suzetrigine represents the first in a new class of non-opioid analgesics that are selective Na<sub>V</sub>1.8 pain signal inhibitors acting in the peripheral nervous system to safely treat pain without addictive potential.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

the FDA release

www.fda.gov

FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain

The FDA approved Journavx (suzetrigine) 50 mg oral tablets, a first-in-class non-opioid analgesic to treat moderate to severe acute pain in adults.
www.fda.gov www.fda.gov

of note, searches on pubmed for Journavx showed this:
1738327001271.png



so dont hold your breath that this will be a gamechanger.
 
Well, here’s hoping it does something

And is not ridiculously expensive
 
I spoke with 1 of reps about this and she went through their PowerPoint including the studies. It is company data so obviously there is risks for bias. The results showed pain relief similar to the results with opioids for the bunionectomy and abdominalplasty group. If I remember correctly there was a fair amount of patients with side effects with the new medication. Here's hoping it moves the needle a little.
 
The actual study in NEJM. It was called VX-548 at the time.

Real but modest effects. With low adverse reactions and no addiction potential, I could definitely see this having a place in multi-modal strategy. Phase 3 under way now for DPN, where it could find utility as well, and likely off label for other neuropathic pain syndromes.
 
so, can it actually be prescribed outpatient? Has anyone tried yet?
 
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Yeah I already have patients asking for it
 
callmeanesthesia said:
They found it non-inferior to pain relief from hydrocodone. Isn’t ibuprofen pretty well proven to also provide equal pain relief to hydrocodone?

For example:
pubmed.ncbi.nlm.nih.gov

Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT02455518.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
Click to expand...

Hydrocodone provides better relief than ibuprofen,( if not taken round the clock)
 
Are you sure with respect to post operative pain?

pubmed.ncbi.nlm.nih.gov

Nonopioid vs opioid analgesics after impacted third-molar extractions: The Opioid Analgesic Reduction Study randomized clinical trial - PubMed

Routine opioid prescribing after dental surgery is not supported. The results of this study confirmed the American Dental Association's recommendations that ibuprofen and acetaminophen in combination should be the first-line therapy for acute pain management. This clinical trial was registered...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov


pubmed.ncbi.nlm.nih.gov

Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial - PubMed

In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
Yes codeine and not hydrocodone.

pubmed.ncbi.nlm.nih.gov

A Prospective, Randomized, Double-Blinded Controlled Trial Comparing Ibuprofen and Acetaminophen Versus Hydrocodone and Acetaminophen for Soft Tissue Hand Procedures - PubMed

Therapeutic I.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
 
I’ve taken hydrocodone for post op pain. I couldn’t tell I took anything. When I take ibuprofen I get relief. Also of note no euphoria at all with hydrocodone. I have also taken oxycodone for post op pain. Significant pain relief and notable euphoria.
 
I know many of these pain medications trials are after dental surgery. Easily to do a study with dental patients but that pain is not the same as post total joint, spine fusion, ankle surgery with osteotomy, etc.

So I don’t accept dental studies comparing pain meds.
 
CVS by me didn't have it in their ordering system yet
 
Laryngospasm said:
I’ve taken hydrocodone for post op pain. I couldn’t tell I took anything. When I take ibuprofen I get relief. Also of note no euphoria at all with hydrocodone. I have also taken oxycodone for post op pain. Significant pain relief and notable euphoria.
Click to expand...
Shoulder scope in college. Nerve block was amazing, and I was told to take a Percocet when I wake up tomorrow AM to stay ahead of the pain. Took a Percocet 5/325mg Sat AM at 0800, puked for 48 hrs. Took Celebrex only from that point fwd. Literally felt nothing from the Percocet other than quite terrible nausea. Awful.
 
my experience was like MitchLevi.

I've taken hydrocodone and oxycodone for various knee surgeries

No real benefit and really bad constipation...

bedrock said:
I know many of these pain medications trials are after dental surgery. Easily to do a study with dental patients but that pain is not the same as post total joint, spine fusion, ankle surgery with osteotomy, etc.

So I don’t accept dental studies comparing pain meds.
Click to expand...
because its early and no one is here:


pubmed.ncbi.nlm.nih.gov

Nonopioid versus opioid analgesia after hospital discharge following cesarean delivery: a randomized equivalence trial - PubMed

Pain score 2-4 weeks after cesarean delivery was lower in women receiving nonopioid analgesics.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
c section. but thats not painful, right?

pubmed.ncbi.nlm.nih.gov

Patient Satisfaction with Nonopioid Postoperative Analgesia in Head and Neck Surgery: A Prospective Randomized Trial - PubMed

In the postoperative population for outpatient head and neck surgeries, there was no significant difference in patient satisfaction and pain control between the opioid and nonopioid arms. Providers should discuss opioid-sparing regimens preoperatively with patients and describe them as effective...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
no difference in satisfaction scores (agree, not truly pain scores but significant nevertheless)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Trial Comparing Opioids versus Nonsteroidal Antiinflammatory Drugs for Postoperative Analgesia in Outpatient Rhinoplasty - PubMed

Therapeutic, II.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
rhinoplasty. ibuprofen was not inferior to hydrocodone

pubmed.ncbi.nlm.nih.gov

Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT02455518.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
single dose, in ER acute extremity pain. no difference at 2 hours between ibuprofen and oral opioid.

pubmed.ncbi.nlm.nih.gov

A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department - PubMed

No analgesic was more efficacious than others 1 or 2 hours after baseline. There was significantly more nausea and vomiting among patients treated with opioids.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
kind of a garbage study, but opioids were not superior to ibuprofen.

but for extremity fractures, which are probably in bedrocks world not as painful as spine surgery, so i guess we should throw this out for that reason.

along with all the other studies that dont align with any preconceived notions.
 
lobelsteve said:
Percocet 5mg after wisdom tooth extraction age 18. N/V x1.
None since, no way. Pain is better than N/V.
Click to expand...

I've never forgotten my experience, so when I give someone Norco or Tylenol #3/4 and they complain of nausea, I believe them.

BTW, in my experience, the worste for nausea is codeine or morphine. Interesting too, because both are closer to the opium and less refined that hydrocodone or oxycodone, and I've always wondered if that is one reason why.

I still don't understand why I had such a bad reaction. I puked all weekend. Could be maybe anesthesia reaction? I don't know, but Sunday afternoon I was worried about sitting in class Monday.
 
mu receptor activation in chemoreceptor trigger zone is the pat answer. morphine is known to be the worst offender for nausea and vomitting - at least it is amongst anesthesiologists...

histamine release may be a contributor.

the reason codeine is emetic is because codeine's main active metabolite is morphine, so essentially one and the same. both of these have a 6- OH component to it which seems to trigger the mu activation at trigger zone much more than drugs that do not have that component (eg hydromorphone).

opium is a catchphrase for latex from an opium plant. it is made of multiple alkaloids, and the primary ones are morphine and codeine. so in some sense opium is morphine, codeine and about 25 alkaloids (like thebaine, papverine).
 
This is the 3 buckets of response to opioids. Lots of people probably around 30-40% based on the available data have significant side effects and take 1 tablet or no tablets after surgery. Another 1/3 or so take a few and hold on to the meds for years "just in case" and then you have 5-20% again depending on the study that take every pill and ask for another script.
 
Ducttape said:
my experience was like MitchLevi.

I've taken hydrocodone and oxycodone for various knee surgeries

No real benefit and really bad constipation...


because its early and no one is here:


pubmed.ncbi.nlm.nih.gov

Nonopioid versus opioid analgesia after hospital discharge following cesarean delivery: a randomized equivalence trial - PubMed

Pain score 2-4 weeks after cesarean delivery was lower in women receiving nonopioid analgesics.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
c section. but thats not painful, right?

pubmed.ncbi.nlm.nih.gov

Patient Satisfaction with Nonopioid Postoperative Analgesia in Head and Neck Surgery: A Prospective Randomized Trial - PubMed

In the postoperative population for outpatient head and neck surgeries, there was no significant difference in patient satisfaction and pain control between the opioid and nonopioid arms. Providers should discuss opioid-sparing regimens preoperatively with patients and describe them as effective...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
no difference in satisfaction scores (agree, not truly pain scores but significant nevertheless)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Trial Comparing Opioids versus Nonsteroidal Antiinflammatory Drugs for Postoperative Analgesia in Outpatient Rhinoplasty - PubMed

Therapeutic, II.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
rhinoplasty. ibuprofen was not inferior to hydrocodone

pubmed.ncbi.nlm.nih.gov

Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT02455518.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
single dose, in ER acute extremity pain. no difference at 2 hours between ibuprofen and oral opioid.

pubmed.ncbi.nlm.nih.gov

A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department - PubMed

No analgesic was more efficacious than others 1 or 2 hours after baseline. There was significantly more nausea and vomiting among patients treated with opioids.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
kind of a garbage study, but opioids were not superior to ibuprofen.

but for extremity fractures, which are probably in bedrocks world not as painful as spine surgery, so i guess we should throw this out for that reason.

along with all the other studies that dont align with any preconceived notions.
Click to expand...

I know you provide COT. So you don’t have a single patient on hydrocodone?
 
1. suzetrigine is for moderate to severe acute pain, so is not an alternative for chronic pain. yet.
2. the patients i have on hydrocodone are those >80 years of age, where long term use of NSAID is not indicated/has significant side effects.
3. the remaining patients on hydrocodone are legacy patients i inherited who have been on it for decades.
4. in truth, i have not initiated COT on any patient younger than 70 in over 2 years.
 
i did nucynta for a few years but stopped about 4 years ago as medicare and most insurances now will not cover.

several patients have had hardships with not being able to afford the $800/month cost. a shame because it did seem to legitimately be better than pure opioids.
 
Ducttape said:
i did nucynta for a few years but stopped about 4 years ago as medicare and most insurances now will not cover.

several patients have had hardships with not being able to afford the $800/month cost. a shame because it did seem to legitimately be better than pure opioids.
Click to expand...
I feel like pharmaceutical companies are really stupid. I mean...I have no idea...but it just seems like if they lowered the price to a reasonable range, much more people would actually pay for the drug...and the company would sell much more and make a ton of money.

But maybe I don't get it. Obviously, these companies have been doing this a long time, but sheesh...seems like a no-brainer to me.
 
epidural man said:
I feel like pharmaceutical companies are really stupid. I mean...I have no idea...but it just seems like if they lowered the price to a reasonable range, much more people would actually pay for the drug...and the company would sell much more and make a ton of money.

But maybe I don't get it. Obviously, these companies have been doing this a long time, but sheesh...seems like a no-brainer to me.
Click to expand...
They don’t set the prices do they? They just negotiate what they’ll pay. I’ve heard it’s the pharmacy benefit managers that are the real devils
 
pharmacy benefit managers are horrible but they are owned by the insurance companies. its a diversion to think it is not United Health Care, for example, that is the problem but this separate nebulous entity.


pharmaceuticals know that they will get their money. insurance companies know they will pay. but insurance companies also know that they will make money by ruthlessly charge people high rates and setting high deductibles. it also helps to delay delay delay as that allows them to recoup more interest, or have victim give up.

its a money grab where people are the victims.
 
I’m pretty sure sometimes the copays are higher than what the insurance pays out. I always ask my patients their copays to try to help manage things for them more efficiently and I’ve asked and been told copays that are more than the discounted rates for imaging and meds.
 
did the patient's insurance cover it?



still nothing on the Epic drug database. i would have to prescribe it the old fashioned way.
 
What about prescribing this pre procedural instead of an Ativan?
 
This is going to be another adjuvant to try, much like gabapentin, methocarbamol, duloxetine, etc... If the side effect profile is good, and we can get 10-20% reduction in pain in, say, 20% of patients, I'm cool with it.
 
Not for anxiety but more for a decrease pain during procedure
 
Malayil said:
Not for anxiety but more for a decrease pain during procedure
Click to expand...

If you want to do that, just prescribe a single opioid pill. For a one time dose of a medication to improve procedure tolerance, you want to be certain that it works.

I do 1/3 of my procedure in an office setting. I find that a 0.5mg Xanax + 5mg hydrocodone/oxycodone definitely helps non Medicare age patients get through an office based cervical RFA
 
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