Replies to post #1124 on Javelin Pharmaceuticals Inc (JAV)

[kcalt]

YMI's fentanyl, belonging to the opioid class, would show respiratory depression/oxygen desaturation due to stim of mu2 receptors in the medullary respiratory centers of the brain. It is also of interest that fentanyl is extremely potent- 80x more potent than morphine. Also, fentanyl PATCHES are contraind. in pts post-surgery due to potential for severe resp. depression. I can only imagine what the risk would be for spray version that is patient-dosed...

Respiratory depression is usually seen with the use of a single, intravenous dose in an opioid-naive patient. In patients taking opioids regularly for pain relief, tolerance to respiratory depression occurs rapidly, so that it is not a clinical problem.

As JAV's products are non-opioid, i would imagine that respiratory depression will be of less risk. However, ketamine does stim opioid mu receptors- but only at high doses that are used to induce anesthesia. It is of interest that ketamine often has effects opposite opioids, ie cardiac output and HR actually increase with anesthetic does of K. As long as none of the patients are allowed to enter stage 2 anesthesia we should be ok :)

[Bio_pete]

<<<<Any thoughts on future FDA caution on safety hold-ups for intranasal PM-150 or intranasal rylomine.>>>

I don't think YMI's problems will come up with PMI-150 or intranasal morphine.

#1. PMI-150's initial indication is for emergency situations so respiratory complications in the post-op setting are not applicable. In addition ketamine is normally not associated with respiratory depression.

Ketamine has gotten a bad rap due to reports of long-lasting psychological effects from single anesthetic doses. It doesn't appear that this type of problem is seen with low dose ketamine, but it will be interesting to see if the FDA has any concerns with using ketamine for pain management.

#2.Intra-nasal morphine, Single dose nasal spray. The dosage is controlled, the nasal mucosa has a maximum saturable level, and it uses JAV's chisys technology. Rylomine reaches peak levels in 20 minutes which also improves its safety profile. A dosage in one person achieves the same blood level or within statistically acceptable levels as another person so its predictable.

The safety risks with Rylomine shouldn't result in any additional concerns seen when administering IV morphine. Its very predictable, but if you give to much morphine by IV, IM, or to much rylomine then your going to encounter adverse events.

[Paullee]

"Any thoughts on future FDA caution on safety hold-ups for intranasal PM-150 or intranasal rylomine given that the FDA has placed YMI's intranasal opioid based pain-killer AeroLEF on clinical hold for safety concerns? How do JAV'S intranasal products stack up to YMI? Since 1/17 and prior to the shelf PR, JAV has been trading down. I am long JAV and any thoughts are appreciated. "



First of all, the FDA had originally allowed the company to file for military and emergency use based on 4 PK studies which showed that had they had any reservations at the time, they would have likely required full blown clinical trials. subsequently, the FDA wanted a small safety study to explore multiple dosing. This is more of an annoyance requirement as the military gives the drug in IV formulation at 50 times the dose of PM-150.

As well, one of the main benefits of Ketamine vs Fentanyl (which is an opiod --ketamine is not) is that it does not depress respiratory responses which if i understand this correctly is what YM is experiencing. In fact, one of the main benefits of using PM-150 in an emergency setting is that without time to adequately triage patients, response workers wouldn't need to worry about killing someone with respiratory problems by giving them an opiod. Note, I am not a Dr