Rapamycin Cost

Let me clear some things up for people considering rapamycin (generic sirolimus).  I am taking it and so are my dogs!!  (I have a very open-minded vet who trusts my judgement.)

Dr. Green, a very impressive individual, gave me my personal prescription for sirolimus.  I have a very good PPO (Blue Cross/Blue Shield).  I took it to CVS, the affiliated pharmacy, and got a great price of about $2.90/mg.  (Remember, you are only going to take about 3-6 mg/week.)  With a PPO you can probably do this also.  CVS wants to meter it to you with a month's worth of doses at a time, but that's just how they do things.  You still have access to the full quantity prescribed. 

With the prescription from my vet for my dogs, I was forced to take to the open sea.  Armed with only a prescription and no insurance, the picture is quite different, but you can still get a good price.  Cutting to the chase, I ended up at Walmart.  The prescription was for 90 mg - price $1440.  But wait! after presenting a coupon downloaded from GoodRX (that's right, just anonymously downloaded and printed) - price $396!!!!  As my vet remarked, that's a hell of a charge for not looking around first!  ($4.40/mg is better than taking a risk buying online, in my opinion.)  Costco is pretty close to that price.  At CVS/RiteAid, etc., you will pay vastly more.

You can't touch the original drug rapamune (Pfizer) unless you are wealthy or go to Canada.  The problem with the online pharmacies is that a lot of them are scams.  Just because they have a website doesn't mean anything.  At least check to see if they have a brick and mortar location.  Example: At one point I was excited by the online infomercials and wanted to take NMN instead of NR; however, when I looked up the reputations of the suppliers only one was unsullied, and on further investigation their brick and mortar location turned out to be a residential dwelling!

FYI, more than one company makes sirolimus.  From CVS the sirolimus was made by Greenstone, LLC, apparently a wholly owned subsidiary of Pfizer.

Hope that helps some people who are considering rapamycin but think it might be out of their reach.  If you know a doctor, great, but if you don't a visit to Dr. Green is worth the trip, and I live in CA!  (round trip less than $300)  Do your homework first and you will learn a great deal.

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    • Dennis
    • Retired USAF pilot, biochemist.
    • Dennis
    • 5 yrs ago
    • Reported - view

    Probably best to follow Dr. Green's advice and not take grapefruit juice since the evidence is weak of it helping and it complicates things.

    Like 1
    • Dennis The grapefruit juice option should be considered if a person is not concurrently taking drugs metabolized by intestinal P450 enzyme complex. The example of statins for cholesterol lowering is the most well known. Barring that, tactical use of grapefruit juice can overcome the poor bioavailability of oral rapamycin.

      After an oral dose 86% of rapamycin is chewed up by the intestinal P450 enzyme and is excreted in feces. Inhibition of this enzyme complex with either ketoconazole or grapefruit juice has been pretty well studied in the oncology literature. In one such study the target dose of rapamycin was 90mg in a once weekly dose which provided the target AUC for the solid tumor being studied. Patients could not tolerate that dose due to GI side effects. It was shown that Ketoconazole administration reduced the required amount of rapamycin to 16mg and administration of grapefruit juice reduced the required amount to 25-35mg rapamycin to reach the same AUC. In other words the intestinal absorption of rapamycin was increased about 300% with grapefruit juice and 500% with ketoconazole. Cohen EE. Clin Cancer Res. 2012;doi:10.1158/1078-0432.CCR-12-0110. 

      The details about grapefruit juice: fresh squeezed is necessary as bottled or canned do not show the same amount of P450 inhibition. Approximately 8 ounces of juice pretty strongly inhibiit the enzyme in about 4 hours and lasts about 24 hours. One large grapefruit provides about 8oz juice.

      Personally, and in select patients, I utilize this P450 inhibition to predictably maximize absorbtion and minimize cost. Consider that 2mg now becomes, in effect, 6mg and the cost savings are large. This is especially true for larger persons. My protocol is to take 8oz freshly squeezed the night before and also the morning of the rapamycin dose. Before deciding about this it would be best to check if any pharmaceuticals a person is taking would be effected by P450 inhibition (only in intestine) or check with your physician.

      Like 5
      • Dennis
      • Retired USAF pilot, biochemist.
      • Dennis
      • 4 yrs ago
      • Reported - view

      Mark Thimineur Well said Mark! Totally agree!

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      • Larry
      • Larry.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur I tried grape fruit juice when I first started Rapamycin three years ago. I would get mouth sores regularly until I stopped the juice addition. I think part of the problem is that GF juice increases the half life of rapamycin so it starts to down regulate mTOR C2, which affects the immune system. I consider mouth sores a possible sign you've pushed mTOR C2 too hard. I'm not an expert like you Mark, just an opinion. 

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    • Larry to answer this with adequate explanation I’ll defer to study of grapefruit juice on drugs called “statins” which treat hypercholesterolemia. Like rapamycin the have low bioavailability (5%) vs 14% for rapa. The reason is both drugs have a first pass effect in which most drug succumbs to the enzymes in the lining of the duodenum. Grapefruit juice irreversibly inhibits the enzyme until more is made which takes 24 hrs to fully reverse. In the presence of grapefruit juice the statin drugs absorb dramatically more with huge increase in plasma concentration. The subsequent hepatic metabolism is unnaffected with the same half life with or without grapefruit. But for the 5 half lives needed to clear the drug the levels are increased thereby increasing the area under the elimination curve (AUC) and, in the case of statins producing deadly toxicity. The same for rapamycin - the AUC is increased but not the elimination half life. If grapefruit juice is used there needs to be dose alteration. Ex: a 5mg dose will effectively become 12.5-17.5mg with juice. Notice it is a range because the increased bioavailability has been measured to be a range of 250-350% - so we are not all the same. 
       

      I’m somewhat concerned that forum participants refer to a milligram number such as “5” as an appropriate dose. The size of a person matters and dosing should be described in terms of mg/kg body weight. A 55kg person is not nearly the same as a 140 kg person in terms of optimal dose. What i have seen suggested ranges from .05 to .1mg/kg although i notice now that Dr. Green has increased his personal dose to .2mg/kg. 
       

      For a 75kg person I would cycle between 2mg and 3mg per week with grapefruit juice making the effective dosing without juice 5mg-7mg up to 7.5-10.5mg. If side effects occur at the 3mg dose the regimen would be altered to have less 3mg representation. Doing simple math one can appreciate the cost savings for people on the heavier side. 
       

      it may be helpful for people to cycle themselves between the higher level and lower level doses and appreciate the dose dependent effects. If choosing grapefruit juice to increase bioavailability make sure to adjust dosing and realize there is a “range” of possible exposure as i have illustrated above. Hopefully this is helpful. 

      Like 5
      • BobM
      • BobM
      • 4 yrs ago
      • Reported - view

      Mark Thimineur 

      great post Mark.

      What too high of dose side effects would you look for?

      cheers

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      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur are you saying Dr Green is taking 15 mg (.2 mg/kg)? Are basing this on actual weight or lean body mass?

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    • BobM The only side effect of note has been mouth sores which I have seen in a very small % of patients taking .1mg/kg dose per week or less. I have seen two patients with an idiosyncratic reaction to even small doses of rapamycin in which they felt fatigue and body pain but this is not a dose dependent issue as they felt it even at 1mg/week. I have not pushed dosage over .1mg/kg purposely but in some patients using grapefruit juice the range of dosage possibility makes it probable that some are over this dosage for brief cyclical periods.

      Like 3
    • Karl I saw a recent interview with Dr. Green state he was now taking 12mg per week and he also stated he had purposely lost 10 pounds making his body weight around 145 pounds or around 66kg so it is slightly less than .2mg/kg but close enough and more than twice his start up protocol of 6mg/week when he weighed over 170lbs. It is interesting. We really don't know optimum dosage for longevity as the rodent studies have  used dosages which are all over the map. The difference between the lowest dietary rapa and highest in the rodent studies is at least 4-fold and all doses are much higher than we are talking about. The lowest dietary rodent regimen showed about 5% longevity and the highest shows about 26% avg life extension - so we really don't know.

      Like 2
      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Mark Thimineur that is the problem with all of this - insufficient data.

      Like 1
    • Karl Agree. For the purposes of self experimenters, it would be helpful if expression of dose be done in the mg/kg such that the observations people are making could be better appreciated in terms of dose response and dosage driven side effects. We are all experiments with an "n" of 1. Even some semblance of standardization among experimenters would be great - particularly for rapamycin.

      Like 2
    • BobM You should look out for a drop of the immune system, which is the effect we know it will cause in transplant patients. 

      Take a Complete Blood Count, and see if your Hematocrit (percent of blood that is red blood cells) is low or falling.  ANEMIA is less than 40% red blood cells, by definition, but in my opinion 42% is already "bad" and will cause that you tire easily.   If your red blood cells in a previous Complete Blood Count was 45% and now it is 43%, this is a clear sign that you should stop rapamycin now, until you have raised red blood cells again.  (ask me how to raise red blood cells.) 

      And you should see if your white blood cells are falling, or if they are already in the "low" range of white blood cells.  

      I have had feedback from persons who have taken 5 mgs rapamycin per week for one year or more, and they did NOT have appreciable changes in red blood cells or white blood cells.   So I know it is entirely possible that 5 mgs in a single dose every 7 days is a good dose of rapamycin for a lot of people.  

      However, there is NO REASON TO RUSH.   We have never taken rapamycin not even once in our life, before, and it might be good and it might be bad for us.   If we start with 3 mgs in a single dose every 5 or 6 or 7 days (take your pick) for a few months, we will be going "in the right direction," with probably some long term benefit.  If it turns out that we should not take anymore rapamycin, in any case the few months that we did take 3 mgs per week might extend our lifespan and healthspan, as Matt Kaeberlein shows us it did in his (excellent) video. 

      https://www.youtube.com/watch?v=2tIGSkzElf0

      And there is plenty of time in the years ahead to take 5 mgs in a single dose one time every 7 days, and get whatever benefit that might give us in the long run, without perhaps a bad side effect (a drop in red or white blood cells) without even monitoring what is the effect that it is having in our particular case.

      NOBODY KNOWS which is the BEST way to take rapamycin in the long run.   Almost everybody is following what Dr. Alan Green and William Faloon do or say... but there is no reason why they are right and you are wrong if you take it in another way.  

      I am grateful to Dr. Alan Green and William Faloon and others for bringing rapamycin to my attention, but I decide what and how much and for how long, for me.   And I am happy to debate what I suggest with  whoever thinks I am mistaken.

      Like 2
    • Ellis Toussier  Enlightening video.  Dr. Kaeberlein reports a translated increase in lifespan of 60% with 90  days of treatment.  This was Rapamycin version RTB101 at 10mg dose.  

      Like
      • Van
      • Van
      • 4 yrs ago
      • Reported - view

      Ellis Toussier It is pretty easy to determine the correct dose of rapa if you are a health person without many underlying conditions.   I have been taking  rapa for almost 3 years. (73 yo male)  I was Dr. Green's 2nd patient.  The most common over dose symptom is mouth sores.  I have had them a couple of times.  They happen in the inner cheek for me and go away after 3-4 days.  This is the first sign that your TOR inhibition is too strong and it is inhibiting TOR 2, not just TOR 1.  In order to get the maximum benefit from Rapa treament you want to inhibit TOR 1 to the max without inhibiting TOR 2 and getting overdose symptoms.  It is in this area that you get maximum life extending benefits and a boost to your immunity without infringing into TOR 2 territory where you can get reduced immunity such as when kidney transplant patients go there frequently,  So, I would suggest your start out at a specific dose, and if no overdose symptoms then up the dose 1 mg week until you get some sores.  Skip a week and take 1 less mg per week and see how your body does at that dose.  If no sores, then you are probably at the maximum TOR 1 inhibition without TOR 2 side effects.  The Goldilocks area.  You can also read the following trial by Dr. Mannick where they experimented on elderly patients with various doses of rapa and they determined ahead of time what the amount of inhibition would be on a particular dose given.  (page 2)  .5 mg daily, 5 mg weekly, 20 mg weekly

      https://sci-hub.tw/https://doi.org/10.1126/scitranslmed.3009892    So in my opinion, finding a proper dose for a healthy person is not that difficult.

      Like 2
      • Karl
      • Karl.1
      • 4 yrs ago
      • Reported - view

      Van you may be correct in your n of 1, but to generalize would be erroneous. Saying that dosing is easy for a drug used for unapproved indication, that has not been adequately studied in humans for this usage is a bit dubious.

      Like 2
    • @Van 

      Hello Van...  How interesting to know that you are Dr. Green's patient.  

      You say it is easy to determine the correct dose of rapa if you are a healthy person without many underlying conditions.  And you say this can be done by looking out for "mouth sores."   This does not seem like the best way to avoid the worst bad side effect that we want to avoid, which is that rapamycin might depress the immune system, as we know it does in transplant patients.  

      The best way to know if it is depressing the immune system is to monitor the immune system, which we can do with Complete Blood Count.   Compare the first with the second, and you see immediately if red blood cells have dropped, and you see immediately if white blood cells have dropped.   If they have dropped, suspend taking rapamycin until you have corrected the drop.

      I would like to know if Dr. Green asked you to take a complete blood count? 

      And did Dr. Green ask you to take a "sirolimus level" blood test?

      I point out that Dr. Green is "mildly anemic" in his words, but he is "very anemic" by my words. As shown on his page https://rapamycintherapy.com his red blood cells and hemoglobin dropped very noticeably from August 2016 to March 2017. And I will guess that his anemia in January 2020 is probably much worse than March 2017, because his raising his dose of rapamycin from 6 mgs per week to 12 mgs per week is an ACT OF DESPERATION, as he feels the worsening effects of anemia.

      His website, however, says he feels great.  So why did he raise his dose from 6 to 12 mgs per week?

      The most obvious secondary side effect of rapamycin that we should be concerned to avoid is A DROP OF THE IMMUNE SYSTEM, and NOT mouth sores.  

      And the best way to monitor if there is a drop of the immune system is to study the "sirolimus level" of transplant patients, and the sirolimus level that various doses cause in us, and a Complete Blood Count before and after a course of rapamycin for several months.  

      Which is why I recommend you should START with 3 mgs in a single dose for a few months, because there is NO REASON TO RUSH.   If you didn't take the optimum dose for (example) 4 or 5 months, there is plenty of time for you to take a higher perhaps better dose in the future.

      And if the complete blood count shows that you have not had a drop of the immune system (white blood cells) then raise to 4 or 5 mgs in a single dose.

      Like 3
    • Ellis Toussier Here is the test from LabCorp. Interestingly, it does reference the 62 hour half life. 

      https://www.labcorp.com/tests/716712/sirolimus-whole-blood

      Incidentally, I recall listening to an extensive Rapa discussion with Peter Attila related to proper Rapa dosage with Matt K. I believe it is still available on his podcasts. They discussed extensively the importance of the trough level of Rapa vs the Peak level. Peter Attia concurs with Dr. Green on the level of ~ 6mg / week which is the dosage Dr. Attia is experimenting with on himself (n of 1). 

      Like 2
      • Dennis
      • Retired USAF pilot, biochemist.
      • Dennis
      • 4 yrs ago
      • Reported - view

      Van Great info Van, thanks much! Has anyone tried the Amazon - "Supersmart - Anti-Aging - Natural Rapalogs - Natural, Effective Inhibitors of mTOR | Non-GMO - 90 Vegetarian Capsules  by SUPERSMART   3.8 out of 5 stars   5 ratings"     I just ordered some after chancing across the add looking for the rapamycin powder which I might order as well. Seems like the Life Extension Foundation might want to try something like these (or offer these)?  

      Price: $49.00 ($0.54 / Count) 
      Like
    • @Sam Biller  

      Hello Sam... Yes, I follow Dr. Peter Attia, and I learn a lot from him.  But even if he is taking 6 mgs., I say we should START with 3 mgs for several months, and we should monitor with a Complete Blood Count periodically, to compare what is happening with red blood cells and white blood cells.   If there is no change, then good for you, you may increase to 4 mgs, or 5 mgs, or 6 mgs.  

      Let's just make it clear that NOBODY KNOWS which is the best dose of rapamycin.  Those of us who have chosen to try rapamycin, based on the gut feeling that it probably does postpone aging, because it has extended lifespan in yeast and worms and fruit flies and mice, as shown in Matt Kaeberlein's video are welcome to try it...

      But WE  KNOW that it lowers the immune system in transplant patients, at the dose that transplant patients take... so THAT is the bad side effect that I say we have to monitor closely, and the way to monitor is to compare two Complete Blood Counts. 

      As for the 62 hour half life... as I wrote before... I took a "sirolimus level" blood test exactly 5 days after I drank 3 mgs rapamycin... the result was 1.51 ng/ml... I took another sirolimus level blood test exactly 5 days later, ie, on day 10.   I expected the result might be two half lives less, that is, half of half of 1.51, which would be about 37.5... but it was .70 ng/ml, so half life in this instance was 5 days, not 2 1/2 days.

      I am not sure what the significance of this is, but maybe half life is 62 hours when there is "a high level" of sirolimus in the blood, and then maybe it gets slower, 125 hours when there is a low level of sirolimus in the blood.   Huh ????

      We can't both be right... or can we ?

      Like 1
      • Van
      • Van
      • 4 yrs ago
      • Reported - view

      Ellis Toussier   Of course, Dr. Mannick did the clinical trial with elderly people to specifically check for rapa's affect on the immune system.  These are people 75 yo+.

      https://www.researchgate.net/publication/270002631_mTOR_inhibition_improves_immune_function_in_the_elderly

      Like
    • Van Hello Van... Well... you know that if *** I *** had been on team of researchers who did the study, I would have added that they all the subjects would have a before and after Complete Blood Count.  

      I can't understand how they didn't include this most basic of blood tests in order to figure out if rapamycin affected their immune system, since WHITE BLOOD CELLS of various types ARE the immune system.  

      It didn't occur to them to check white blood cells ?  

      Like
    • Ellis Toussier have you read the work of Mikhail Blogosklonny? He seems to have researched rapamycin better than anyone. He is quite accessible on 
      twitter and readily answers questions. Perhaps better than your n of 1

      Like 2
    • Paul Beauchemin    I don't know what question you would like for me to ask Mikhail Blagosklonny?    Which is my n=1, what have I written that makes you think I don't have a large enough sample, of what ?

      I think I am in a different dimension than Mikhail Blagosklonny, and than Dr. Alan Green, because I am not relying on a single magic pill that lengthens lifespan and healthspan. 

      Just drink your magic pill one time every seven days, and wait until you should have gotten old, and hopefully you didn't get so old, yet.   

      You don't have to do exercise, you don't have to eat correctly to keep blood sugar controlled, you don't have to monitor blood sugar, you don't have to try to keep your cells from damage so that they won't divide prematurely so you can keep your telomeres long... It might even help you to lose weight !!!

      All that is necessary is to drink the right dose of your magic rapamycin, and hopefully you will postpone Old Age.  

      That is their version of anti-aging, that is what they write.   Rapamycin is their entire anti-aging program, maybe plus metformin, maybe plus senolytics too.

      I will tell you why metformin works: metformin lowers average blood sugar, and so it "mimics calorie restriction"... Calorie restriction, of course, also lowers average blood sugar. 

      I think there is a good chance that rapamycin alone might work, as planned, and so I have added rapamycin to my own personal anti-aging program...

      I will tell you why I think I am ahead of Dr. Alan Green and Bill Faloon.   I learn from them, but they don't learn from me.   I do what they do, and also what they haven't dreamed of doing yet.

      I also do exercise, I also inject hormones, I also eat correctly, I also take hyperbaric oxygen (usually once every 7 days) and various other anti-aging therapies (eg, Thermage, Fraxell, Botox, etc.) some of which are just superficial (Botox) and others which in fact turn back the clock a bit (Thermage and Fraxell actually cause collagen and skin rejuvenation.)

      I DO believe that rapamycin will postpone Old Age, and I DO believe it is almost magic.

      But I also believe in correct nutrition, exercise, vitamins and minerals, take care of your skin, get rid of parasites, get rid of toxic metals, replace all the hormones that go DOWN with age, and take care not to lose neurons in your brain and all of your body.

      So, of course, if you are ANEMIC you must force up your red blood cells, which you can do with EPO (ErithroPOyetin) but try to find a doctor who will prescribe EPO to you, and you've got a big hurdle to cross.

      Like 2
    • Ellis Toussier Curious what you think of the Ketogenic Diet for longevity? What is your dietary protocol? 

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      • Cynda
      • Cynda
      • 3 yrs ago
      • Reported - view

      Ellis Toussier I read with great interest your views on aging. I am new here and just started on Rapamycin weeks ago. I am in Mexico 5 months of the year and can get it here rapamune(by Phizer) and know its legit. I contacted Dr. Green to see if he would remotely work with me. No he would not.....Anyway I digress....I believe like you that most of the "fountain of young" comes from exercise and nutrition and taking care of our bodies (sleep, HRT, little stress, etc). I do not take Metformin due to my exercise regime and per Peter Attia and Rhonda Patrick (who I greatly respect both) if we are lifting weights and exercising like we should we do not need Metformin. In fact one person above said he couldn't build muscle and that is due to Metformin ...its in the literature. Basically use what you need that can enhance and do ALL you can to delay aging. I very much would like to know more about you and get in touch with you to find out what more I can do. You are so well versed on the blood work that I am not. My e-mail is ckvhondo@gmail.com and would love to here if you have a site or office that I might take advantage of.

      Like
    • Cynda if you can get rapamycin yourself without a prescription? Why would you want Dr Greens help with? What else does he provide that you cant do yourself?

      Like 1
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