Rapamycin common uses, half-life, side effects and more

Rapamycin is sirolimus. It is a prescription drug that dials down a cell growth pathway known as mTOR. It is best known as a transplant immunosuppressant. Oral sirolimus is FDA approved to prevent kidney transplant rejection and to treat a rare lung disease called lymphangioleiomyomatosis. Separate prescription versions exist as a skin gel for tuberous sclerosis and as an injection for a rare cancer. Longevity users take low oral doses once weekly to try to slow aging. That use is off label and unproven. It still reaches people through a prescription and a compounding pharmacy. Nonprescription powders sold online sit outside that supply chain.

• Kidney transplant rejection prevention
• Lymphangioleiomyomatosis treatment
• Weekly longevity dosing that is off label and unproven
• Topical treatment of tuberous sclerosis skin growths and skin aging
• Specialist use for some vascular malformations and overgrowth syndromes
• Immune aging and age-related disease research

Once daily for approved uses and once weekly for off label longevity use

Approved kidney transplant dosing starts with a 6 mg oral loading dose then 2 mg once daily in lower risk patients. Higher risk regimens start with up to 15 mg on day one then 5 mg once daily. LAM starts at 2 mg once daily and is titrated to a whole blood trough of 5 to 15 ng/mL. Longevity use is a low oral dose once weekly. A user survey found 6 mg weekly the most common dose. Most people cluster around 5 to 8 mg. The reported spread runs from 1 to 20 mg. Compounded rapamycin is often taken higher at about 5 to 15 mg weekly. The PEARL trial used 5 mg and 10 mg of compounded rapamycin once weekly for 48 weeks. No anti-aging dose target has been validated. Topical rapamycin is a different use. The approved 0.2% gel treats tuberous sclerosis skin growths. Compounded 0.1 to 1% creams are applied once daily for skin aging. Very little reaches the bloodstream at those strengths.

• Take it consistently with or without food because food changes how much is absorbed
• Longevity users usually start low near 1 to 3 mg weekly and titrate up over weeks
• Users commonly pause it during an active infection or illness

Terminal half-life is about 62 hours after repeated oral dosing in stable kidney transplant patients. A single dose in healthy volunteers ran longer at roughly 80 hours. The long half-life means one dose keeps measurable drug in the blood for several days. That span is the rationale for weekly longevity dosing.

Approved tablets are stored at room temperature between 20 and 25 degrees Celsius and kept out of light. The oral solution is refrigerated between 2 and 8 degrees Celsius and used within a month of opening. Compounded products follow the pharmacy label.

• Mouth ulcers are the most common complaint and rise with dose even on weekly schedules
• High cholesterol and triglycerides are common at daily doses and still need monitoring on weekly dosing
• Blood sugar changes, anemia, low platelets, low white cells, swelling, or protein in the urine can occur
• Slow wound healing, fluid pockets under the skin, and wound splitting are labeled risks
• Serious risks include infection, lymphoma, skin cancer, and lung inflammation
• Topical creams mostly cause mild local skin irritation and are absorbed too little to cause the body-wide effects

Rapamycin binds a small protein inside cells called FKBP12. The pair then blocks a master growth switch known as mTORC1. mTORC1 senses nutrients, insulin, and growth signals and drives protein and fat synthesis and cell growth. It also blocks autophagy. That is how the cell clears its own worn parts. Rapamycin does not block a second version called mTORC2 right away. Steady daily exposure disrupts it over time. Animal work points to that mTORC2 disruption as the main reason for higher blood sugar and insulin resistance. Weekly dosing aims to hit mTORC1 while letting mTORC2 recover between doses. Whether that selective effect holds in people is unproven.

The strongest evidence is in mice rather than people. Rapamycin reliably extends lifespan in genetically varied mice across independent labs and doses. It works even when started late in life. Human evidence is short-term and limited to safety and biomarker studies. The PEARL trial gave 5 mg and 10 mg of compounded rapamycin weekly for 48 weeks to healthy adults aged 50 to 85. Weekly dosing looked reasonably safe over the year. The main goal of reducing visceral fat failed. The few positive signals were secondary and self-reported in a small subgroup of women. That trial was run by a company that sells rapamycin. Related mTOR drugs once raised hopes for immune aging. The one large confirmatory trial failed. No human trial has shown that rapamycin extends lifespan or prevents age-related disease.

• It suppresses the immune system and carries a boxed warning for higher infection and cancer risk
• It slows wound healing and is usually paused before surgery and until wounds heal
• Pregnancy and breastfeeding are not advised because it can cause fetal harm
• Grapefruit and strong CYP3A4 or P-gp inhibitors can sharply raise blood levels and toxicity
• Rifampin, carbamazepine, phenytoin, and St John's wort can lower blood levels and weaken the effect
• Live vaccines should be avoided during treatment