#1

I started Rapamycin a couple of weeks ago at a 1mg dose planning to increase gradually to 4-5mg over the next couple of months. But I noticed side effects immediately…

  • 1st 1mg dose: took at lunchtime and felt fine all day. Woke up the next day with a headache and feeling slightly nauseous. Took paracetamol, got on with my day fine and had no problems the next day.

  • 2nd 1mg dose (taken 1 week later): took at lunchtime again and felt fine all day. Woke up the next day with a very mild sensation of a headache but easily tolerable (better than 1st dose). Was unusually hungry by breakfast. After dinner that night I felt extremely nauseous (saliva filling mouth like I was about to vomit - I don’t have a weak stomach - last time this feeling happened to me was probably 15 years after drinking too much alcohol. I woke up the following day feeling very hungry again and unusually tired. I’ve read people talk about a euphoric tiredness and I suppose it was something like that all day (not that I was euphoric but it might have been kinda nice if I hadn’t had to work). But I did definitely feel overall kinda “suppressed” for a good couple of days by this 2nd dose and didn’t even want to go for a walk. I also paradoxically couldn’t fall asleep on the day I felt the most tired (again, I don’t have sleep problems normally)

Does it make sense that the 2nd dose might have a bigger impact than the first? Has anyone heard of side effects on such a tiny starting dose of Rapa?

I have 1 theory why I might be hyper-sensitive to Rapa in case anyone’s interested: I have a genetic disease that results in extremely high blood levels of TGF-B which contributes to pathology of the aorta in my family. TGF-B is predicted to activate mTOR (well, more than predicted in some mouse studies). So perhaps if my mTOR is relatively over-activated, I could be more sensitive to its inhibition. Or perhaps other people have also had side effects from a 1mg dose?

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#2

Yes, some of us have had effects at 1mg. You are not alone in this.

For me, my first dose came with brainfog, head pressure, and dizziness. While that specific constellation of effects did not repeat, over years of rapamycin I’ve done pulses of differing doses, and had other noticeable effects – though sometimes none – at 1mg dose.

Many of us have found that our effects change across pulses. Sometimes subtly, sometimes not. Yours may as well.

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#3

Wish we had real blind placebo controlled studies. I am willing to bet that 90% of so called side effects of rapamycin are placebo effects

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#4

Side effects like this are rare, but some people have reported them. Side effects at low doses seem more likely if people are smaller (i.e. of small stature and weight).

Are you taking any other foods / supplements or medications that might interact? Rapamycin Interactions with Other Food, Drinks, Supplements and Drugs

Any pre-existing medical conditions?

#5

Interesting because I’m tall (6’4’') but not heavy (90kg). Only other medication I take is losartan 50mg every morning (been taking for a decade with no side effects). Supplements:

omega-3
magnesium
vitamins: C, D, K2, methylated B-vitamin complex
nattokinase
NAC
glycine
creatine
whey
collagen peptides
psyllium husk

Only pre-existing medical condition is the familial aortopathy I mentioned although this is mild/controlled so it wouldn’t seem to anyone like I had a problem (can lift weights, run etc)

As the other person said, it’s hard to rule out placebo but the effects certainly feel very real! The one night of nausea particularly was very out of character and I’ve had a general tiredness since the 2nd dose that is so noticeable that it would really surprise me to learn it was a placebo effect. Might give my body a break next week so I know it’s fully cleared from my system and try again some other time (perhaps even a 0.5mg dose at first!)

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#6

You can’t really go for 0.5 mg dose as the pills can’t be split without making them ineffective. All the sirolimus tablets have a coating or technology to increase bioavailability (allowing the sirolimus to get through the stomach to the small intestine to be absorbed), so you can’t split them.

It cold be a placebo effect. I see no obvious issues with your supplements.

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#7

Oh thanks I didn’t know that about splitting the pills although 1 pharmacy around here actually offered me 0.5mg pills to start with but I insisted on the 1mgs

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#8

I don’t think that was the issue, so they should be able to be safely split:

#9

95% (or more) of the rapamycin market in the USA is likely generics, which do not use the Elan Pharmaceuticals’ nanocrystal technology that the brand name Pfizer Rapamune uses: Rapamycin and NanoCrystal Formulations. and even for Rapamune they don’t recommend you split, crush, etc. the tablet: “Do not crush, chew, or split RAPAMUNE tablets. Tell your doctor if you cannot swallow RAPAMUNE tablets. Your doctor can prescribe RAPAMUNE as a solution.” of course, that could be for commercial reasons and not just functional reasons, but I could not find any websites claiming it is possible to split Rapamune without effecting the bioavailability. You’d really need to look at the pharmacokinetics of the Elan technology to better understand this issue, and I’m not so interested in it. https://labeling.pfizer.com/showlabeling.aspx?id=139§ion=MedGuide

All the generics use some sort of coating to increase bioavailability from what I’ve seen. Break that covering and I’m pretty sure you lose the bioavailability benefits (and thus 95% of the benefits). Do you have any scientific evidence to the contrary?

#10

The rapamycin is in the coating with rapamune, and the core is inert.
I don’t know whether the nanocrystals or nanoparticles (solid dispersions?) are much affected by splitting, I mean they are intact in the other areas of the pills?

#11

Source for this claim?

#12

The inert tablet core is composed of lactose monohydrate, macrogol 8000, magnesium stearate, and
talc. The tablet coating is composed of several layers of coatings consisting of a nanodispersion
(containing the active substance and a stabiliser), macrogol 20000, glycerol monooleate,
pharmaceutical glaze, calcium sulphate anhydrous, microcrystalline cellulose, sucrose, titanium
dioxide, brown iron oxide (E172), yellow iron oxide (E172), α-alpha tocopherol, povidone, carnauba
wax and red printing ink

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#13

Good find! But most of us here are not taking rapamune because of the high cost. I am not even sure it’s still available in the USA.

#14

Ths is most easily resolved if someone simply split their pills before taking a rapamycin serum blood test they were going to take anyway, and see if the serum amount is as usual. I’m guessing it is.

Biocon has film coating, not enteric coating, so probably the same thing there.

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#15

I don’t know if this is related to your problem but based on this paper (on everolimus, not sirolimus), this might not be the right strategy if low-dose has actually more sympathetic activation than high dose (might explain the nausea?): Dose-dependent effects of rapa on anxiety?

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#16

Hi,

I’m new to rapa, too. I’m taking 1 mg and splitting a 2 mg generic for rapamune. I’m having significant effects (pos and neg) after only one dose last week. I have a friend who is doing same experiment.

My symptoms: unable to sleep first night. Had the feeling of coming down with upper respiratory infection on that first night. Calm but fatigued for several days. A few new aches and pains for first few days, but my chronic rt. shoulder pain has all but resolved. Also, I developed a scalp rash which I had attributed to rapa, but now wonder if I suddenly developed an allergy to castor oil (which I had used on my scalp the day prior to first dose of rapa).

I am surprised by the idea that rapa can’t be split and don’t know if that’s accurate. I will split today’s dose again, but will graduate to a full pill 2 mgs next week.

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#17

I was on Rapamune for years, but 3-4 mo ago I was notified by my pharmacy that Rapamune is not going to be available bc Pfizer stopped producing it. I called Pfizer and they confirmed.

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#18

Oh and I had a few brief moments of nausea on day 1, too.

#19

Very interesting thanks. honestly I’m not sure I’d have the coverage to go straight for a higher dose now that I’ve experienced 1mg side effects - think I’d be more inclined to switch to a biweekly 1mg to each dose a chance to fully clear from my system before layering the next dose on top of it, and then gradually decrease the 2-week cycle to a weekly one.

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#20

“Calm but fatigued for several days” sounds exactly my experience too - didn’t really have any aches/pains to begin with that I could have noticed disappearing though. Good to know others are having similar experiences on low doses, but I’m leaning on starting fresh with a 2-weekly cycle to begin with just because it was the 2nd dose that gave me far more noticeable side effects