#1088

I recently started taking Rapamycin and had unexpected side effects: after the 3rd dose (only 2mg) I was knocked out with 38,5°C of fever for a whole day.

But step by step: I am 44 years old, male, 171m, 62kg, fit and healthy.

I am taking Rapamune (Pfizer). No other supplements on the day of Rapamycin. Am taking it on empty stomach in the morning, only with a glass of water.

    • 1st dose 1mg, made me feel extremely exhausted for almost 4 days.
    • 2nd dose one week later, again 1mg: this time I was fine, only slightly down on the first day
    • 3rd dose one week later: 2mg. Diarrhea one hour after taking it. 3hours after taking it I got a fever (38,5°C) and was knocked out in bed the whole day. Weird feeling in the mouth and a discoloration of my tongue: greyish-green. Today is the second day of my 3rd dose and the fever is gone, but I still feel very exhausted. No other side effects.

I would very grateful for any ideas of what may be going on here, since I seem to be pretty alone with this strong reaction despite careful dosing.

6 Likes
#1089

I am not an expert or a doctor but here’s my advice: don’t be in a rush to maximize the benefit rapamycin. You have time.

If you are exhausted for 4 days after a dose then 7 days seems too soon for another dose until rapa doesn’t beat you down so much. If you feel terrible after taking Rapa make sure it is fully out of your body before the next dose; accumulation is not good.

Good luck

7 Likes
#1090

I’d stop taking rapamycin, see the doc in person, and run a few tests. Clearly your body is very sensitive to rapamycin. Also rapa induced fever is a possibility, it just probably doesn’t happen often with such a low dose in once a week application.

6 Likes
#1091

Sorry you are having problems. Your symptoms are puzzling. You could be allergic to rapamycin just as some people are allergic to some microorganisms. Fever isn’t one of the side effects that I can find listed.

“Common allergic symptoms reported with rapamycin include rash, itching, swelling, and difficulty breathing.”

Most common side effects; “feeling tired, weak, or lacking energy while taking rapamycin. Skin rash or acne: Rapamycin can cause skin rashes, acne, or other dermatological issues in some patients. Nausea, diarrhea, or abdominal pain: Gastrointestinal side effects like nausea, vomiting, diarrhea, and abdominal pain are common with rapamycin use. Elevated cholesterol and triglyceride levels: Rapamycin can increase blood lipid levels, which may require additional medication to manage. These side effects can vary in severity and may depend on the dosage and duration of rapamycin treatment, as well as individual patient factors.”

You need to seek medical advice however difficult that may be if you want to continue to take rapamycin.

5 Likes
#1092

Thank you all for the helpful replies! I am not with a doctor in this unfortunately, so I better be careful.

One question: does anybody know if it would be advisable to take half a pill, since they are clearly made to pass the stomach. If I cut it in half it would already dissolve in the stomach. Not recommended, I guess. Correct?

1 Like
#1093

Assuming your tablet is coated, that’s an enteric coating designed to increase bioavaialability, meaning to make it more potent in your system than it would be otherwise. If you want less–less potency–the only downside to cutting it in half is that you might not get anywhere near 1/2 of the effective dose of a full pill, but far less.

Others will doubtless disagree with me here, but as someone who has been sensitive to rapa at low doses, I say go ahead and experiment–it’s your pill, after all. Deciding to cut it in half and see if you can tolerate that, even though halving it disrupts the enteric coating, then titrating up, seems to me a perfectly reasonable thing to try.

4 Likes
#1094

@sol This makes a ton of sense. On that note, incase my thinking is right and this works, @Hans, I’ve been putting my cat’s cancer pills into an empty gel cap … FYI, empty gelcaps are easy to find, but delayed release gelcaps are also available.

2 Likes
#1095

You’re using Pfizer rapamune version of sirolimus. It is made with a special technology from Elan Technologies (now Alkermes). You can read up on this technology here: Rapamycin and NanoCrystal Formulations

This technology protects the sirolimus from stomach acids to increase the bioavailability. What I don’t know is the impact of pill splitting on this type of pill. I’ve googled around a bit to look for the impact of pill splitting on Elan nanocrystal technology but have not found much. I would recommend you continue the hunt on this.

They describe this technology as: “coated micro particles” which suggests to me its like tiny enteric capsulated crystals, so a tablet is just an aggregate of those crystals…

It seems that you might be able to pill split with this technology because small bits of sirolimus seem to be bundled in a protective coating, so at a higher level pill splitting might work. (note: I don;t think this is the case with other versions of sirolimus, for example my Zydus and Biocon sirolimus seem to have some sort of “skin” on them for protection from stomach acid, so if you break their coating you likely lose all protection).

You may want to do a blood sirolimus test after pill splitting the Rapamune tablets and trying them, to see if its raising your blood sirolimus levels still (and thus is “working”). See this thread: How to get a Rapamycin (sirolimus) Blood Level Test

You can read up further on this at the links below:

Progress in the Study of Drug Nanocrystal
https://www.ingentaconnect.com/content/govi/pharmaz/2015/00000070/00000012/art00001?crawler=true

https://www.sciencedirect.com/science/article/pii/S0378517321005135

4 Likes
#1096

Thanks again for your kind advise! I will report back how things develop over time!

2 Likes
#1097

I would say that you would not want to break the protective coating. It’s there for a reason. Even with a coating, only about 10% of the sirolimus is absorbed by the body. That’s why taking grapefruit juice neutralizes the enzyme that breaks sirolimus down so that the bioavailability goes up to 30-35%. If you break the coating, my guess is you would get results close to the Siroboon brand of sirolimus which has abysmal bioavailability (10% of other brands). So your 0.5 mg would effectively become 0.05 mg which isn’t going to do much if anything outside of a placebo effect.

I guess you could then put the split pill in an enteric capsule to jury rig a protective layer, but I wouldn’t do it.

4 Likes
#1098

More GFJ the stronger the effects. I take close to 700ml each time.

1 Like
#1099

I’m happy to report a positive side effect I noticed this weekend. Normally come sandal season in Indiana I’m embarrassed to show my feet in open toed shoes until I’ve had a good pedicure and polish. With this and that happening I hadn’t got it done yet to kick off the season when my husband decided he wanted to go boating. I panicked because my feet have looked pretty embarrassing to me for the last 10 years with thick and at times discolored nails. I keep my feet clean and my toenails trimmed of course. My feet are actually looking really good now and this is the first time in a decade I haven’t been self conscious about people seeing my feet in an all natural state!

image
image1920×1440 240 KB

11 Likes
#1100

Yes, my toenails and fingernails have take on a really deep satin shine…with very pink… healthy coloring.

3 Likes
#1101

I’m going to catch up to you eventually sir! I’m thrilled to not have deep ridges and discoloration anymore.

1 Like
#1102

I noticed my nails cleared up too but wasn’t sure exactly how lol. But it is probably since I started rapamycin.

4 Likes
#1103

LOL you made me look at my feet for the first time in a quarter century haha

7 Likes
#1104

Not only did my toenails become better… my toenails have actually again become more consistent thick and better. Something one day I notice was the plantar’s foot calluses I had for years also vanished.

My whole foot skin has gotten softer. Usually the soles dry out and crack in the wintertime, but not since rapamycin use.

7 Likes
#1105

I must say those are some gorgeous toenails! Mine didn’t look that good when I was 10 :). I had no idea this could be a nice side effect!

3 Likes
#1106

What I think happens with feet is that they suffer more pressures and age faster than cells in other parts of the body. Hence when you start getting the cells energy levels up they start doing the things they would ordinarily. I found that a better line was defined between dead cells and live cells. Hence rather than having a large amount of dead skin I would lose the really bad skin and retain the better quality cells.

4 Likes
#1107

Feet must get the worst of everything:

Worst blood flow (furthest from heart)
Worst treatment (crunched up toe boxes; disfiguring over time)
Lack of sunshine and fresh air (I don’t wear sandals)

I’ve been thinking of reverting to a childhood habit of laying in the floor with my legs up a wall. It would have to be good for a variety of things.

I’ll do that from now on for at least 10 minutes a day.

5 Likes