My Journey Begins

[EPguy]

Had my 1st Besremi dose yesterday. I did it at Drs office but had to stick myself since it is patient supplied meds. I know zero about needles except they are shiny and sharp and best unseen. But here I'm required to look at it. No pain at all, even less than the Covid shot. (compare Shingrix, you know that one went in)

I now know that it uses a: 30G x 1/2" needle.

Dr was re-reading the instructions as I'm his 1st Bes. My 1st doses are 50 mcg as a soon to be ex HU user. It's a "tolerance dose" rather than a "therapeutic dose". It will increase assuming all goes well. But a surprise was in store:

He said "you get the bubble out, start at 500, then stick it in and press the syringe to 450". If you're paying attn this is news. The instructions say to dump all of the juice till it shows my dose of 50 then stick it and press till it stops.

He was virtually unable to see the related instructions about trashing $6000 of somebody's money. I asked several ways and this is to be our procedure. I trust his advice as he is a long time Hem and MPN specialist.

He confirmed it is a standard syringe and gave me the set of "30G 1/2" needles, see pic. These are nice and small. This multi use procedure matches the UK procedure of reusing the BES syringe, so there is precedent. But in a further plan, we will use it all up. This is possible because of another surprise:

The expiry is a year from now. It's actually printed in two places giving a range of Dec 2022 and Feb 2023.

Assuming I reach the higher doses it could soon be that I get only two, or even one, dose from each 500 syringe. But for now we are sleek and efficient.

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*Edit* See my reply below for more discussion of the dose procedure.

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I had mild flu like last night with 99+ temp. It's ok today, just my usual MPN symptoms. I hope INF helps with that.

I will continue my HU dosing and 50 Mcg Bes for another two shots.

I was pleasantly surprised how smooth and low friction the syringe action was. It makes easy to control the dose.

My understanding lately the goal is to titrate to the max tolerated dose to get the best molecular benefit. This is different than HU for example where you don't use more than the minimum needed. I hope also to get the same very good hematological response that I have on HU. (my bloods almost look like a normal person my Dr said) Sure don't feel like one.

[hunter5582]

Glad to hear the first injection went smoothly. It really is easy and painless.

Interesting to note that apparently in the EU instructions there is a procedure to use the syringe twice (with different needles) provided the syringe is used within 30 days. Don't really know much about that, but interesting if that is how it works. They also have the 250mcg syringes over there. Much better pan.

My syringes come with a cap and the needle separate. I take off the cap, put on the needle, waste a bunch of Besremi/money, and do the injection. Very easy, but I cringe at wasting 80% of $7,500. Oh well!

All the best on your Besremi journey.

[EPguy in reply to hunter5582]

I get the idea that my Dr considers the approach to be "most rational" medical practice (my take on the procedures)

[Meatloaf9 in reply to EPguy]

How many doses will you get out of one syringe since you will be changing the needle and reusing the besremi syringe. I think that is what you are doing, forgive me if I am reading that wrong. It would be nice if you could get 10 of the 50 mcg doses from one syringe since it's expiration date is a year from now. Best to you on tolerating the besremi and its effectiveness for you.

[EPguy in reply to Meatloaf9]

It would be 10 doses at 50. Two qualifiers: There should be some waste for each as I splirt the juice out of the needle. Also I expect (hope) that the dose will increase before all 10 at 50ml would be used. I will not expect to cut the HU till that happens.

My Dr was clear that that this is not precision, there is slop (my word) in the req't. We did not quantify that, I guess by definition slop can't be quantified.

[Alexbits]

I use Pegasys in the same way. One syringe, multiple needles. It works well.

[EPguy in reply to Alexbits]

Does your syringe look like this PEG syringe?

PEGSyringe

[Alexbits in reply to EPguy]

Yes

[EPguy in reply to Alexbits]

It appears that syringe has wider spaced markings and could be easier to control. It does look easier to use than the Bes one to me. Makes sense since it has smaller total contents (180 vs 500) so is a smaller diameter. Here is an image of the Bes syringe. Can't really tell here, but it is wider than a normal vax one.

BesremiDetail

[Alexbits in reply to EPguy]

I see. Well, it seems you have to be extra careful with this one. From my experience, good lightning conditions help a lot.

[FG251 in reply to EPguy]

Good news!Thanks for posting that pic, too. I had wondered about the convex syringe and may have administered a tad too much! Now I’ll measure the dose from the flat outside edge.

[EPguy in reply to FG251]

As my Dr said, this level of precision is not required here, but we all want to do it right. At 50mcg, a tiny twitch of the hand will make a big % difference. So it likely requires twitch free hands, as I discuss here.

[Bonston]

Interested. I am starting on Besrimi. So instead of spilling everything out you just go from 500 to 450? But if you do that aren’t you injecting 450. I’m confused.

[EPguy in reply to Bonston]

You bring up a good point, as it is potentially confusing. I had to spin my head on it for a bit. In fact it requires good hand/eye coordination since you start at 500 and (in this dosing example) press till it reaches 450 then stop. There is no mechanical limit, only your hand skills on an area that can be hard to see.

The Euro instructions and device are quite different and include a mechanism to pre-set the dose. No precise hand control required. (comments from our Euro members are welcome here) See screen shot here from:

ema.europa.eu/en/documents/...

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In fact the US Bes application was rejected last year in part because FDA did not like the instructions for administrating the dose.

From March 2021

fiercepharma.com/drug-deliv...

<<The FDA has asked for more information about how the provided Instructions For Use for our prefilled syringe will help patients and healthcare providers administer the treatment>>

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It seems plausible and even likely the wasteful procedure we see in the US is from FDA requirements. They either didn't like the complex Euro device and/or a procedure that requires too much physical precision.

I can say myself that it is not easy to contort yourself while watching the fine syringe gradations and while pressing and stopping the plunger. Only the low friction action I described above makes it possible. The mask I wore in the office also blocked my view, but this is not an issue at home.

If one sets the plunger position with the syringe right at your eyes, as the US instructions call for, it would be signif easier, and FDA may have felt the same. Similarly the Euro style device may have seemed too complex for FDA's liking.

My Dr. knows I am a skilled technician artist etc (see my post on that elsewhere) So he likely felt comfortable with his instructions to me. I think most users would have no trouble with it. But not everyone retains steady hands and flexibility as we age (I will join that group someday) and so the FDA likely felt the multi use procedure is not broadly advised for the population that would use it.

Besremi Euro Dosing

[Meatloaf9 in reply to EPguy]

From looking at the europa link you provided it appears to me that the US version would be much easier to use multiple times. You might need an engineering degree to use the European syringe. I think it might have been designed to prevent multiple uses.

[EPguy in reply to Meatloaf9]

The Euro device is a mechanical mystery to me and I have such a degree. But I've not had a sample. We have some members here using it, I hope we hear from them.

[DottyDaisy]

Oh, oh, EPguy, your report is music to my ears, well to my eyes I suppose.Here in the UK with my Peg, I have repeatedly been told that it is "not recommended" to use the same syringe more than once. However one of the nurses who had carefully told me that same thing, using that exact same wording, nonetheless then gave me a big handful of of fresh needles so I am now happily injecting from 90 down to 45 for the first dose and then using the fresh needle ten days later for the rest. With a bit more practice and confidence, I am thinking that a weekly dose of 30 might be even more effective because of Peg's 7-day half life.

[Hopetohelp in reply to DottyDaisy]

I think we are all learning from EPguys experience. I will have a few questions for my haematologist next time

[EPguy in reply to DottyDaisy]

It is a grey area. But based on the various experts advising us, is seems broadly safe to do multi injections. As I posted here, I think it could be Dr's judgement of the patient's physical condition. For example at one extreme my mother with dementia and shaky hands would certainly not be allowed to do multi, much less any, self injections if she were to need them, while in another less extreme example it may be ok to do the single injection up to a mechanical stop, where for example a house mate sets the plunger position.

As discussed here, the Bes device seems particularly delicate in metering the dose in awkward positions.

[Orangeboykitty]

To encourage you, I just had my fourth dose of Besremi, 50mcg, and went to the hematologist for a CBC and checkup. I'm not taking any other med. Stopped Pegasys when I started Besremi. Surprisingly, my numbers were perfect, just on that low dose, so no need to increase.

[DottyDaisy in reply to Orangeboykitty]

Well that's good news OBK. And presumably, after 4 doses, your consistently good results cannot be residual effects from whatever you were taking before.

[Orangeboykitty in reply to DottyDaisy]

That seems to be a pattern with me and I've been on this journey 8.5 years. The lowest dose of PV meds is usually enough to keep my numbers in check, but I get almost every side effect possible. When I went to the hematologist he noticed that I was speaking more slowly than usual. That's because I was slightly dizzy from the Besremi. And my face was a little puffy. Pegasys also kept my numbers in check but gave me diarrhea and made me intolerant to both gluten and the protein in dairy products. Seems that the side effects of Besremi are more tolerable, not pleasant but tolerable. I've been through most of the PV meds currently available and it's always been the same story except for HU, which I couldn't tolerate at all. Hoping the Besremi side effects will diminish in time.

[EPguy in reply to Orangeboykitty]

We've heard from a few members of Bes being more tolerated than PEG. The mfg claims exactly this, could be they're right. I've posted on the comparison before.

[EPguy in reply to Orangeboykitty]

Thanks for the info. That is a surprise that 50mcg holds your numbers and a good sign of general health in this regard.

Is your Dr ok then to leave the dose there? My understanding is INF works best at the highest tolerated dose if molecular response and its hoped for effects thereof are the goal. My specialist said this also. This is different from most meds, and strange to me. HU a good conventional example, where the min dose that works is the goal.

[Orangeboykitty in reply to EPguy]

For now he's leaving it the way it is. Going back in 4 weeks.

[Elizka in reply to EPguy]

I wonder how you find that "highest dose"? Meaning, if your numbers are good at say 275 mcg, what is a better/higher does that could give you the molecular response. And how do you tell outside of the blood counts? The syringes are 500 mcg is that the goal if you can tolerate it?

[EPguy in reply to Elizka]

You're correct that 500 is the max single dose.

One confusion is the FDA approval on efficacy was for hematological response. Molecular response that gets us all excited was not a goal (endpoint) of the study. And the ContiPV study was used only for safety data so its clear and satisfying molec data was not part of the FDA approval. (PEGINVERA vs hematological resp was use for efficacy)

Here is the actual dosing guide, but as above, it cares only about your CBCs.

drugs.com/dosage/besremi.html

<<Increase the dose of BESREMi by 50 mcg every two weeks (up to a maximum of 500 mcg), until the hematological parameters are stabilized (hematocrit less than 45%, platelets less than 400 × 109/L, and leukocytes less than 10 × 109/L)>>

The dosing is reduced if there are adverse effects as in the link's table 1: <<Table 1 Dose Modifications for BESREMi Adverse Reactions>>

I asked my Dr, part in jest, about using a min dose of INF and "cheating" by topping up the CBC numbers with low dose HU. He said that defeats the purpose of getting molec response via INF, quite reasonable. But molec response is an "off label" subject that the drug maker can't talk about.

We've seen that CHR (full blood response) on INF correlates to molecular response. So my take on all this is our Dr may want to push to the max dose that does not overly suppress CBCs while hammering the allele to the extent possible. (this my opinion on an off label Rx consideration) Problem is molec resp doesn't often show clear results till a year or more.

[EPguy in reply to Orangeboykitty]

Thanks again for the promising hope.

[ggrana in reply to Orangeboykitty]

That’s great news for you ! I’ve done 4 injections already and my numbers havent budged yet , and I’m on 3 hydroxyurea pills a day until we see counts start to go down( which are at one million on all this medication). I pray Besremi will help me so I can wean off the chemo pills.

[Orangeboykitty in reply to ggrana]

I was on Pegasys before and my numbers have been pretty much controlled for a long time now. My issue has been side effects. BTW - when my platelets were one million from many phlebotomies back in 2014, I was given Anagrelide to bring them down quickly so I could have surgery. Worked beautifully!

[Wyebird]

I do hope it suits you. Well done for administering it yourself. It’s such a scary event first time.

[EPguy in reply to Wyebird]

Plenty stressful. I'm sure after enough of these it will be easy as walking on two feet.

[Wyebird]

I don’t know if I’m repeating myself but put an ice pack on jab site for 10 mins prior to injection

[DottyDaisy in reply to Wyebird]

So more than one way to kill the cat. (What an awful expression!) But either way, whether you warm up the Peg or cool down the site, your equalizing the temperature.

[Wyebird in reply to DottyDaisy]

I put the ice pack on my tummy it numbs the area a bit. 🤗

[EPguy in reply to Wyebird]

Interesting option, makes sense to equalize the temp in either direction. It would seem if the juice is getting reused, fewer temp cycles on it would be preferred, although my Dr is fine with it. Maybe I'll split the diff. A little bit cool on the tummy and a bit of warming on the shot.

In any case, there was no sensation at all in the procedure. I expect as the dose increases its temp will become a more sensitive issue.

[EPguy in reply to Wyebird]

I did my 2nd Bes shot last night and tried the ice with the syringe warmed up only partly. It worked well, thanks for the suggestion.

[Wyebird in reply to EPguy]

Bril🤗

[Meatloaf9]

Is equalizing the temperature of the injection site and the material only to prevent discomfort of the shot or does it have anything to do with the absorption of the medicine or the efficacy of the injection???

[EPguy in reply to Meatloaf9]

My Dr's office said it is only for comfort.

[DottyDaisy in reply to Meatloaf9]

Well that's a thought, isn't it. I just take it out first thing and put it on the table. Then realise I may not have drunk enough water. So I pour out another half litre and tank into that. Then I'll maybe stab myself at lunchtime. That's okay if it's the second half of the 90 mcl syringe. I try to be more careful if it's the first 45 and will have to go back in the fridge.OH and I may be sounding a bit gung ho today because I just got the results from the bloods taken at my pre-op on Thursday. PLATELETS 406. Oh yes !!! This should mean a new hip within the month. Drinks on me guys.

[EPguy in reply to DottyDaisy]

The Besremi instructions have a 30 minute max room temp period. But I think a lot of this is more flexible than it appears.

[Meatloaf9 in reply to DottyDaisy]

That's great news, if I were in the UK I would take you up on that drink. Good luck with the hip.