With strong CYP3A4/P-gp inhibitors
Safety flag
Strong CYP3A4 or P-gp inhibition can markedly increase sirolimus exposure and toxicity.
Interaction evidence source All research profiles
Prescription immunosuppressant / longevity
Sirolimus
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Also known as Rapamycin
Routes represented in the knowledgebase: Oral.
Educational overview
FDA-approved immunosuppressant; anti-aging use is off-label and has not established lifespan or healthspan benefit in humans. Infection and malignancy risks are substantial.
Sirolimus, also called rapamycin, is a macrolide compound first isolated in the 1970s from Streptomyces hygroscopicus in soil from Easter Island (Rapa Nui). It is classed as an mTOR inhibitor and immunosuppressant: bound to the intracellular protein FKBP12, it blocks mechanistic target of rapamycin complex 1, which slows T-cell proliferation in response to interleukin-2 and dampens cell growth and protein synthesis broadly. Because mTOR signaling also regulates autophagy and nutrient sensing, sirolimus became the reference compound in aging biology after it extended lifespan in genetically diverse mice in the National Institute on Aging Interventions Testing Program, the first drug to do so when started late in life.
As a transplant and rare-disease drug, sirolimus has decades of randomized trial and post-marketing data. As a longevity intervention, human evidence is early. The largest study, the PEARL trial published in 2025, randomized 114 adults aged 50 to 85 to placebo or one of two weekly doses of compounded rapamycin for 48 weeks; adverse events were similar across groups, the primary endpoint of visceral fat did not differ, and secondary improvements in lean mass and pain appeared in women at the higher dose. Smaller trials of related mTOR inhibitors reported improved influenza vaccine responses in older adults. No human trial has measured lifespan, and a 2025 evidence review concluded that an anti-aging benefit in people remains unproven.
Sirolimus is FDA-approved, originally in 1999 under the brand Rapamune, for prophylaxis of organ rejection in kidney transplant recipients, and since 2015 for lymphangioleiomyomatosis; a topical gel is approved for facial angiofibroma in tuberous sclerosis. Oral tablets and solution are prescription-only in the United States, the European Union, and comparable jurisdictions. The label carries a boxed warning for immunosuppression, increased susceptibility to infection, and possible development of lymphoma and other malignancies, and it advises against use in liver or lung transplant because of excess mortality and bronchial anastomotic dehiscence. Anti-aging prescribing, typically once weekly, is off-label, and compounded capsules are not approved products.
The label reports a mean terminal half-life of roughly 62 hours in stable kidney transplant patients, so the drug persists for days after each dose. Sirolimus is metabolized by CYP3A4 and transported by P-glycoprotein; strong inhibitors, inducers, and grapefruit juice change exposure substantially, and the label says live vaccines should be avoided during treatment. Tablets are stored at room temperature protected from light; the oral solution is refrigerated, protected from light, and discarded one month after the bottle is opened. A dose log for sirolimus commonly records product form, lot, dosing day, co-medications, and any infection or mouth ulcer, and an inventory record tied to bottle-opening dates supports the solution's one-month limit.
- Category
- Prescription immunosuppressant / longevity
- Routes represented
- Oral
- Storage context
- Follow the product or pharmacy label; requirements vary by route and formulation.
Published literature
No verified PubMed or DOI link is available for this entry.
Safety evidence
Common or reported: edema, high triglycerides or cholesterol, hypertension, diarrhea, nausea, stomatitis, anemia.
Serious or important: serious infection, impaired wound healing, renal dysfunction, interstitial lung disease, thrombotic microangiopathy, embryo-fetal toxicity.
Safety evidence sourceInteraction evidence
These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.
With strong CYP3A4/P-gp inducers
Safety flag
Strong CYP3A4 or P-gp induction can reduce sirolimus exposure and cause treatment failure.
Interaction evidence sourceWith grapefruit
Safety flag
Grapefruit inhibits intestinal CYP3A4 and can increase sirolimus exposure.
Interaction evidence sourceWith live vaccines
Safety flag
Immunosuppression can permit vaccine-related infection and reduce vaccine response.
Interaction evidence sourceCommon questions
Is rapamycin the same as sirolimus?
Yes. Rapamycin is the original name given to the compound isolated from Easter Island soil bacteria, and sirolimus is its international nonproprietary name as a drug. Rapamune is the brand of the FDA-approved tablets and oral solution, and generic sirolimus is also marketed. Everolimus and temsirolimus are chemically modified derivatives, sometimes called rapalogs, with different half-lives and approved indications.
Does rapamycin extend lifespan in humans?
Not shown. Sirolimus reliably extends lifespan in mice, including when started late in life, and this animal evidence drives interest in it. In humans, the 48-week PEARL trial of 114 older adults found safety similar to placebo and some secondary improvements in lean mass and pain among women, but it did not measure lifespan and its primary endpoint was not met. A 2025 evidence review concluded that a human anti-aging benefit remains unproven.
What are the main risks of sirolimus?
The approved label carries a boxed warning for immunosuppression leading to infection and to lymphoma and other malignancies. Common effects in transplant trials include mouth ulcers, raised cholesterol and triglycerides, impaired wound healing, peripheral edema, anemia, and low platelets. Interstitial lung disease has been reported. Exposure rises markedly with CYP3A4 or P-glycoprotein inhibitors and grapefruit, and falls with inducers such as rifampin.
Is rapamycin for anti-aging FDA approved?
No. Sirolimus is approved for kidney transplant rejection prophylaxis and lymphangioleiomyomatosis, with a topical form for tuberous sclerosis angiofibromas. Any prescription for healthy aging, longevity, or general wellness is off-label, and compounded low-dose capsules sold by telehealth services are not approved products. Off-label prescribing is lawful for a licensed clinician, but no regulator has evaluated sirolimus for an aging indication.
Further reading
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
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