Sirolimus and everolimus bind the same immunophilin as which other transplant drug?
Choose an answer, then check it.
Clinical Pharmacology · Transplant Medications
mTOR Inhibitors
On this page 6 sections
In 30 seconds
Sirolimus and everolimus are the mTOR inhibitors used in transplant medicine. They bind the same immunophilin as tacrolimus, FKBP-12, but instead of blocking calcineurin they block mTOR, a downstream growth signal, so T cells cannot divide even when IL-2 is present. That makes them a calcineurin-sparing option when kidney toxicity is a problem, but it brings a signature side-effect profile tied to blocked cell growth: poor wound healing, fluid collections, mouth sores, and lipid problems.
The college version
Sirolimus (rapamycin) and its relative everolimus form a class distinct from calcineurin inhibitors, though the two share a starting step. Like tacrolimus, sirolimus enters the T cell and binds FKBP-12, the same immunophilin. There the resemblance ends. The tacrolimus-FKBP-12 complex inhibits calcineurin, stopping the transcription factor NFAT from switching on IL-2 production. The sirolimus-FKBP-12 complex instead inhibits mTOR, a kinase that drives the cell through the cycle once growth signals like IL-2 have bound their receptor. IL-2 can still be made and bind its receptor, but the signal dies at the next step: the cell cannot progress from G1 to S phase, so clonal expansion of activated T cells never happens. Remember it this way: calcineurin inhibitors stop the signal to produce IL-2; mTOR inhibitors stop the response to IL-2.
Clinical niche
Because these drugs do not inhibit calcineurin, they lack the direct nephrotoxic mechanism limiting cyclosporine and tacrolimus, so they are a common substitution when a recipient develops declining kidney function or other calcineurin-inhibitor toxicity — a calcineurin-sparing regimen. The same antiproliferative effect that halts T-cell expansion also blocks proliferation of vascular smooth muscle and tumor cells, which is why related compounds coat some drug-eluting stents and why these agents also serve as oncology drugs.
Adverse effects
The defining safety issue is impaired wound healing, since mTOR inhibition slows the proliferation and migration tissue repair requires. Combined with a tendency to cause lymphoceles at the surgical site, this is why mTOR inhibitors are typically avoided right after surgery and started only once incisions have healed. Other hallmark effects include hyperlipidemia, painful mouth ulcers, proteinuria, peripheral edema, bone marrow suppression, and non-infectious interstitial pneumonitis that can mimic pneumonia but does not respond to antibiotics, instead requiring dose adjustment.
Monitoring and interactions
Both drugs have a narrow therapeutic window and require trough level monitoring. They are metabolized through CYP3A4 and are substrates of P-glycoprotein, carrying the same interaction burden as calcineurin inhibitors — azoles, macrolides, and grapefruit raise levels, while enzyme inducers lower them. A key interaction: cyclosporine raises sirolimus levels, so the two are dosed with a several-hour gap rather than given together.
General transplant themes
As with all maintenance immunosuppressants, patients on mTOR inhibitors need lifelong attention to infection risk, malignancy screening, and strict adherence, since missed doses risk rejection while excess exposure risks toxicity and infection.
Eli explains
The same idea, in plain words
Explain it like I’m 10
Think of a T cell as a factory that wants to build an army of copies of itself. Tacrolimus cuts the phone line so the factory never gets the "start building" order. Sirolimus and everolimus let the order arrive fine, but jam the assembly line itself, so no copies roll off even though the order came through. Both drugs grab the same helper protein first, then jam a different machine. Because these drugs slow growth everywhere, not just in immune cells, surgical wounds heal more slowly, which is why doctors wait until after surgery to start them.
Check yourself
2 review questions from the chapter. Try each one, then open the answer.
A transplant patient stable on tacrolimus develops worsening kidney function attributed to the drug itself. Why might the team switch part of the regimen to sirolimus?
Show answer
They are not intrinsically nephrotoxic the way calcineurin inhibitors are
Switching part of the regimen to an mTOR inhibitor can reduce calcineurin-inhibitor dose while still suppressing T-cell proliferation, potentially protecting the kidney from further damage.
A patient taking both cyclosporine and sirolimus is found to have unexpectedly high sirolimus levels. What interaction explains this, and what administration strategy addresses it?
Show answer
Cyclosporine raises sirolimus blood levels
Cyclosporine interferes with sirolimus metabolism and transport, pushing levels up, so the two drugs are given several hours apart rather than at the same time.
Quick check
3 questions here. Answers stay hidden until you check.
At what point in T-cell activation do mTOR inhibitors act?
Choose an answer, then check it.
Why are mTOR inhibitors usually delayed until after surgical wounds have healed?
Choose an answer, then check it.
Study tools & related lessonsRelated
Educational content only. It is not medical, legal or professional advice. Found an error? Tell us.