{"site":"Sirolimus Rx","url":"https://sirolimusrx.com","format":"evidence-manifest/v1","claim_count":69,"claims":[{"id":"RAP-001","text":"FDA approved Rapamune (sirolimus) oral solution on September 15, 1999 under NDA 021083 (sponsor of record today: PF Prism CV, a Pfizer entity); Rapamune tablets are approved under NDA 021110, and both remain Prescription products.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021083","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/entity","https://sirolimusrx.com/faq","https://sirolimusrx.com","https://sirolimusrx.com/comparison"]},{"id":"RAP-002","text":"The lymphangioleiomyomatosis (LAM) indication was added to Rapamune by efficacy supplement S-055, approved May 28, 2015.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021083","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://sirolimusrx.com/monograph"]},{"id":"RAP-003","text":"The FDA label states sirolimus is indicated for prophylaxis of organ rejection in renal transplant patients aged 13 years or older, and for the treatment of patients with lymphangioleiomyomatosis.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/entity","https://sirolimusrx.com/faq","https://sirolimusrx.com/decision_aid"]},{"id":"RAP-004","text":"Rapamycin (sirolimus) is an FDA-approved prescription immunosuppressant (Rapamune) for organ-transplant rejection prophylaxis. Taking it for longevity is off-label and unproven.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021083","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/entity","https://sirolimusrx.com","https://sirolimusrx.com/copy","https://sirolimusrx.com/faq"]},{"id":"RAP-005","text":"The sirolimus label carries a boxed warning: increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression, and only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use it.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com","https://sirolimusrx.com/tools"]},{"id":"RAP-006","text":"The boxed warning also states sirolimus is not recommended in liver or lung transplant patients: liver transplant use was associated with excess mortality, graft loss, and hepatic artery thrombosis, and lung transplant use with cases of bronchial anastomotic dehiscence, most fatal.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph"]},{"id":"RAP-007","text":"In the two pivotal renal-transplant trials, lymphoma/lymphoproliferative disease occurred in 0.7 to 3.2 percent of sirolimus-treated patients versus 0.6 to 0.8 percent of azathioprine and placebo controls; the label warns malignancies particularly of the skin may result from immunosuppression.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-008","text":"Label dosing for renal transplant at low to moderate immunologic risk is one 6 mg loading dose on day 1 followed by 2 mg daily; at high immunologic risk, a loading dose of up to 15 mg on day 1 followed by 5 mg daily.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/comparison","https://sirolimusrx.com/tools","https://sirolimusrx.com/faq"]},{"id":"RAP-009","text":"For LAM the label's recommended initial dose is 2 mg per day, adjusted to sirolimus trough concentrations of 5 to 15 ng/mL.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/comparison","https://sirolimusrx.com/tools"]},{"id":"RAP-010","text":"The label recommends therapeutic drug monitoring for all patients, with trough concentrations monitored at least 3 to 4 days after a loading dose.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools","https://sirolimusrx.com"]},{"id":"RAP-011","text":"The mean terminal elimination half-life of sirolimus after multiple dosing in stable renal transplant patients was estimated to be about 62 plus or minus 16 hours.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools","https://sirolimusrx.com/pk"]},{"id":"RAP-012","text":"Oral bioavailability of sirolimus solution is approximately 14 percent; tablet bioavailability is approximately 27 percent higher than the solution, and the two forms are not bioequivalent, though clinical equivalence was demonstrated at the 2 mg dose.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/pk","https://sirolimusrx.com/faq"]},{"id":"RAP-013","text":"Sirolimus partitions extensively into red blood cells (mean blood-to-plasma ratio 36 plus or minus 18), is about 92 percent bound to human plasma proteins, and has a mean volume of distribution (Vss/F) of 12 plus or minus 8 L/kg.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/pk"]},{"id":"RAP-014","text":"Sirolimus is a substrate for both CYP3A4 and P-glycoprotein; the label says to avoid concomitant use with strong CYP3A4/P-gp inhibitors such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin, and with strong inducers such as rifampin or rifabutin.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools","https://sirolimusrx.com/faq"]},{"id":"RAP-015","text":"The label states grapefruit juice inhibits CYP3A4-mediated metabolism of sirolimus and must not be taken with sirolimus or used to dilute the oral solution.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools"]},{"id":"RAP-016","text":"When taken with cyclosporine, the label recommends taking sirolimus 4 hours after the cyclosporine dose.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools"]},{"id":"RAP-017","text":"The label warns that increased serum cholesterol and triglycerides requiring treatment occurred more frequently with sirolimus than with azathioprine or placebo in the pivotal trials.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools"]},{"id":"RAP-018","text":"The most common adverse reactions in renal transplant patients per the label include peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, and arthralgia.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-019","text":"In the LAM clinical study, adverse reactions with incidence of 20 percent or more were stomatitis, diarrhea, abdominal pain, nausea, nasopharyngitis, acne, chest pain, peripheral edema, upper respiratory tract infection, headache, dizziness, myalgia, and hypercholesterolemia.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-020","text":"The label warns of fluid accumulation and impairment of wound healing (including lymphocele and wound dehiscence) in patients receiving sirolimus.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-021","text":"The label warns of interstitial lung disease and non-infectious pneumonitis (including bronchiolitis obliterans organizing pneumonia and pulmonary fibrosis cases) with sirolimus.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-022","text":"The label recommends periodic quantitative monitoring of urinary protein excretion because of proteinuria risk, which increased in a trial converting maintenance renal transplant patients from calcineurin inhibitors to sirolimus.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools"]},{"id":"RAP-023","text":"The label states patients on immunosuppressive therapy are at increased risk for skin cancer and should limit sun and UV exposure with protective clothing and high-SPF broad-spectrum sunscreen.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-024","text":"The label says live vaccines should be avoided during sirolimus treatment, listing measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid as examples.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools"]},{"id":"RAP-025","text":"The label lists male infertility as a warning: azoospermia or oligospermia may occur with sirolimus.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-026","text":"The label states sirolimus can cause fetal harm based on animal studies and mechanism of action; it was embryo/fetotoxic in rats at sub-therapeutic doses, and pregnant women should be advised of the risk.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph"]},{"id":"RAP-027","text":"Per the label, sirolimus is contraindicated in patients with hypersensitivity to sirolimus; hypersensitivity reactions including anaphylaxis and angioedema have been associated with it.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/decision_aid"]},{"id":"RAP-028","text":"Sirolimus oral solution must be stored refrigerated at 2 C to 8 C (36 F to 46 F) protected from light and used within one month of opening the bottle; tablets are stored at room temperature.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-029","text":"Hyperglycemia, diabetes mellitus, and new-onset diabetes mellitus appear in the sirolimus label's adverse-reactions experience, including after conversion to sirolimus.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools"]},{"id":"RAP-030","text":"Sirolimus is sold in more approved forms than Rapamune: HYFTOR, a 0.2 percent topical gel (NDA 213478), is approved for facial angiofibroma associated with tuberous sclerosis in patients 6 and older; FYARRO (NDA 213312) is an intravenous protein-bound sirolimus; SCOMARA (NDA 218528) is an approved topical cream; and multiple oral generic ANDAs exist.","source_url":"https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22sirolimus%22&limit=50","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/decision_aid","https://sirolimusrx.com/entity"]},{"id":"RAP-031","text":"Everolimus, the closest rapalog, is FDA-approved as Afinitor (NDA 022334, oncology indications including advanced breast cancer and neuroendocrine tumors) and as Zortress (NDA 021560, kidney and liver transplant rejection prophylaxis), and its mean elimination half-life is approximately 30 hours.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2150f73a-179b-4afc-b8ce-67c85cc72f04","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/comparison","https://sirolimusrx.com/faq","https://sirolimusrx.com/monograph"]},{"id":"RAP-032","text":"Sirolimus is PubChem CID 5284616.","source_url":"https://pubchem.ncbi.nlm.nih.gov/compound/5284616","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://sirolimusrx.com/entity"]},{"id":"RAP-033","text":"The label describes sirolimus as an mTOR inhibitor immunosuppressant; sirolimus binds FKBP-12 and the complex inhibits mTOR activation, suppressing cytokine-driven T-lymphocyte proliferation.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/entity"]},{"id":"RAP-034","text":"The label instructs that sirolimus be taken once daily, consistently with or without food.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph"]},{"id":"RAP-035","text":"The label warns about co-administering cannabidiol with sirolimus: monitor closely for increased sirolimus blood levels and adverse reactions.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"fda-label","grade_label":"FDA label","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools"]},{"id":"RAP-040","text":"In the NIA Interventions Testing Program, rapamycin fed from 600 days of age (roughly a 60-year-old human's life stage) extended mouse lifespan at all three independent test sites: based on age at 90 percent mortality, an increase of 14 percent for females and 9 percent for males.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2786175/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison"]},{"id":"RAP-041","text":"Harrison 2009 reported these were the first results demonstrating pharmacological extension of lifespan in both sexes of a mammal, and that disease patterns of rapamycin-treated mice did not differ from controls.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2786175/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies"]},{"id":"RAP-042","text":"In the ITP's second lifespan test, rapamycin started at 9 months of age extended median survival by an average of 10 percent in males and 18 percent in females across three sites; resveratrol and simvastatin, tested in parallel, had no significant survival effect.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3021372/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-043","text":"At a threefold higher dietary dose (42 ppm), rapamycin increased mouse median lifespan by 23 percent in males and 26 percent in females; the effect was dose and sex dependent, larger in females at every dose tested, and metabolically distinct from dietary restriction.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4032600/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/comparison","https://sirolimusrx.com/faq"]},{"id":"RAP-044","text":"A 3-month transient course of rapamycin in middle-aged mice increased remaining life expectancy by up to 60 percent; the same paper also identified a female dose that did not extend lifespan and shifted cancer prevalence toward aggressive hematopoietic cancers.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4996648/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-045","text":"In the ITP, metformin alone at 0.1 percent of diet did not significantly extend mouse lifespan, while metformin combined with rapamycin (14 ppm) robustly extended lifespan.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5013015/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-046","text":"Chronic rapamycin in mice substantially impairs glucose tolerance and insulin action by disrupting mTORC2; reduced mTORC1 signaling extended lifespan independently of those glucose defects.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3324089/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-047","text":"In mice, an intermittent rapamycin dosing schedule had minimal effects on glucose tolerance and a reduced impact on the immune system compared with daily dosing; the rapalogs everolimus and temsirolimus inhibited mTORC1 with less impact on glucose tolerance.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4717280/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison"]},{"id":"RAP-048","text":"Metformin co-treatment alleviated rapamycin-induced glucose intolerance in female genetically heterogeneous mice; the authors note ITP data showing mice on metformin plus rapamycin live at least as long as mice on rapamycin alone.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5892694/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-049","text":"Feeding rapamycin to adult Drosophila extended lifespan through the TORC1 branch via autophagy and translation changes, and TOR-pathway inhibition extends lifespan in yeast, nematodes, and flies.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2824086/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies"]},{"id":"RAP-050","text":"In a 10-week randomized placebo-controlled trial in 24 middle-aged companion dogs, a non-immunosuppressive rapamycin dose produced no clinical side effects versus placebo, and echocardiography suggested improvements in age-related measures of both diastolic and systolic heart function.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5411365/","grade":"animal","grade_label":"Animal","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies"]},{"id":"RAP-051","text":"The TOR genes were discovered in yeast in 1991 through rapamycin-resistance genetics; rapamycin itself was isolated in 1975 from a Streptomyces hygroscopicus strain found in an Easter Island soil sample and named after the island (Rapa Nui).","source_url":"https://pubmed.ncbi.nlm.nih.gov/1715094/","grade":"qualitative","grade_label":"Qualitative report","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/entity"]},{"id":"RAP-055","text":"In a placebo-controlled pilot in 25 generally healthy adults aged 70 to 95 (mean 80.5), rapamycin 1 mg daily for 8 weeks produced no changes in glucose tolerance, insulin secretion or sensitivity, cognition, or physical performance; statistically significant but not clinically significant decrements occurred in several red-cell parameters, and side effects in the rapamycin group were limited to facial rash (1), stomatitis (1), and gastrointestinal issues (2).","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5869166/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison"]},{"id":"RAP-056","text":"The 2014 elderly immune-function RCT used everolimus (RAD001), not sirolimus: it enhanced influenza vaccine response by about 20 percent at relatively well tolerated doses and reduced PD-1-expressing T lymphocytes.","source_url":"https://pubmed.ncbi.nlm.nih.gov/25540326/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison","https://sirolimusrx.com"]},{"id":"RAP-057","text":"The 2018 phase 2a trial in 264 elderly subjects used a low-dose combination of BEZ235 (dactolisib) plus RAD001 (everolimus) for 6 weeks; it was associated with a significant decrease in reported infection rates for a year (P=0.001), upregulated antiviral gene expression, and improved influenza vaccine response.","source_url":"https://pubmed.ncbi.nlm.nih.gov/29997249/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison"]},{"id":"RAP-058","text":"The phase 3 trial of RTB101 (dactolisib) in 1,024 adults 65 and older failed its primary endpoint: clinically symptomatic respiratory illness occurred in 26 percent on drug versus 25 percent on placebo (odds ratio 1.07, p=0.65). The phase 2b analysis had shown 19 percent versus 28 percent laboratory-confirmed infections (odds ratio 0.601, p=0.02).","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8102040/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-059","text":"PEARL, a 48-week decentralized randomized placebo-controlled trial of compounded rapamycin 5 mg or 10 mg once weekly in 129 enrolled healthy adults, found no significant change in its primary outcome, visceral adiposity by DXA (p=0.942); adverse and serious adverse events were similar across groups.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com","https://sirolimusrx.com/comparison"]},{"id":"RAP-060","text":"PEARL's secondary outcomes: lean tissue mass (p=0.013) and self-reported pain (p=0.015) improved significantly for women on 10 mg weekly, and self-reported emotional well-being (p=0.023) and general health (p=0.004) improved for the 5 mg group; no other significant effects were observed.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-061","text":"PEARL was run by AgelessRx, a longevity telehealth company; its authors are AgelessRx employees and shareholders, which the paper discloses.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-062","text":"A 2023 survey compared 333 adults using off-label rapamycin with 172 non-users; the authors describe it as initial evidence that rapamycin can be used safely in adults of normal health status and state that limited data exist on side effects or efficacy in this context.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10187519/","grade":"human-obs","grade_label":"Human observational","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison"]},{"id":"RAP-063","text":"In real-world longevity cohorts, compounded rapamycin had roughly one third the bioavailability of the commercial product (estimated 31.03 percent of the same milligram dose); real-world users took commercial doses of 2, 3, 6, or 8 mg or compounded doses of 5, 10, or 15 mg, blood levels peaked about 2 days after dosing, and inter-individual variability was substantial.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12397450/","grade":"human-pk","grade_label":"Human PK","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq","https://sirolimusrx.com/comparison","https://sirolimusrx.com/tools"]},{"id":"RAP-064","text":"In the US pivotal renal-transplant trial (719 patients), adding sirolimus to cyclosporine and prednisone cut 6-month efficacy failure to 18.7 percent (2 mg) and 16.8 percent (5 mg) versus 32.3 percent with azathioprine; biopsy-confirmed acute rejection fell to 16.9 and 12.0 percent versus 29.8 percent.","source_url":"https://pubmed.ncbi.nlm.nih.gov/10963197/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-065","text":"In the worldwide phase 3 renal-transplant trial (576 patients), biopsy-confirmed acute rejection at 6 months was 24.7 percent (2 mg/day) and 19.2 percent (5 mg/day) with sirolimus versus 41.5 percent with placebo, reductions of 40.5 and 53.7 percent.","source_url":"https://pubmed.ncbi.nlm.nih.gov/11213073/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies"]},{"id":"RAP-066","text":"In the MILES trial (89 LAM patients), lung function stabilized on sirolimus: FEV1 slope was +1 plus or minus 2 mL per month on sirolimus versus -12 plus or minus 2 mL per month on placebo (P<0.001); after stopping sirolimus, the decline resumed and paralleled placebo.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3118601/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-067","text":"In the TUMORAPA trial, kidney-transplant patients with prior squamous-cell carcinoma who switched to sirolimus developed new SCC at 22 percent versus 39 percent staying on calcineurin inhibitors (relative risk 0.56); the sirolimus group also had 60 serious adverse events versus 14, and 23 percent discontinued the drug.","source_url":"https://pubmed.ncbi.nlm.nih.gov/22830463/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-068","text":"A 2021 review of the rapamycin aging literature calls the 2009 mouse result the first evidence that a pharmacological agent could impact aging when administered later in life, and concludes it is time for preclinical studies to focus on taking rapamycin to the clinic.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8190242/","grade":"review","grade_label":"Review or guideline","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/studies","https://sirolimusrx.com/faq"]},{"id":"RAP-070","text":"No completed randomized trial of sirolimus or any rapalog has tested lifespan, mortality, or age-related disease incidence as a primary endpoint in a healthy aging population. The one completed longevity-population RCT of sirolimus (PEARL) had a body-composition primary endpoint and did not meet it, and the largest rapalog outcome trial in older adults (RTB101 phase 3) failed its respiratory-illness primary endpoint.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com","https://sirolimusrx.com/faq"]},{"id":"RAP-071","text":"No validated method converts the ITP's dietary rapamycin doses in mice (4.7 to 42 ppm of food) into an equivalent human oral milligram dose; this site does not perform that conversion. Human dosing anchors are the label's doses and trough targets.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4032600/","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com/tools","https://sirolimusrx.com/comparison"]},{"id":"RAP-072","text":"Weekly low-dose rapamycin for longevity has no outcome trial behind it. What exists: mouse data showing intermittent dosing reduces metabolic and immune side effects, PEARL's 48-week safety experience on 5 to 10 mg compounded weekly, a survey of 333 users, and real-world blood-level data. None of these measured lifespan or disease outcomes.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4717280/","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq","https://sirolimusrx.com","https://sirolimusrx.com/comparison"]},{"id":"RAP-073","text":"The three landmark 'rapamycin' human aging-immunity trials all tested other molecules: everolimus (RAD001) in 2014, dactolisib (BEZ235) plus everolimus in 2018, and RTB101 (dactolisib) in the 2021 phase 3. Sirolimus itself was not the study drug in any of them.","source_url":"https://pubmed.ncbi.nlm.nih.gov/25540326/","grade":"derived","grade_label":"Derived from cited data","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/comparison","https://sirolimusrx.com/faq","https://sirolimusrx.com"]},{"id":"RAP-074","text":"This page's study table has 23 rows, each labeled with species and with the exact compound studied; 11 rows are human studies, and 3 of those human rows tested a rapalog other than sirolimus.","source_url":"self","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://sirolimusrx.com","https://sirolimusrx.com/monograph","https://sirolimusrx.com/copy"]},{"id":"RAP-075","text":"This site cites 33 fetch-verified sources for rapamycin: 24 peer-reviewed and 9 government (FDA labels, FDA records, ClinicalTrials.gov, PubChem), 100 percent peer-reviewed or government.","source_url":"self","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://sirolimusrx.com","https://sirolimusrx.com/copy","https://sirolimusrx.com/monograph"]},{"id":"RAP-076","text":"Zero rows in this site's study table report a completed human trial with a lifespan, mortality, or disease-incidence primary endpoint for longevity use; the table says so instead of hiding it.","source_url":"self","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://sirolimusrx.com","https://sirolimusrx.com/monograph","https://sirolimusrx.com/faq"]},{"id":"RAP-077","text":"Steady state at a fixed daily or weekly oral dose is reached after roughly four to five half-lives; with a 62-hour half-life that is about 11 to 13 days, which is why the label times trough checks days after any change rather than hours.","source_url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=384cb547-55a4-47fc-a0a6-054c18a51b84","grade":"derived","grade_label":"Derived from cited data","used_on":["https://sirolimusrx.com/monograph","https://sirolimusrx.com/tools","https://sirolimusrx.com/faq"]}]}