Sirolimus (Rapamycin)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-SIROLIMUS |
|---|---|
| Type | Drug |
| Aliases | RapamuneSirolimusСіролімус (Рапаміцин) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | DIS-LAM |
| Sources | SRC-MILES-MCCORMACK-2011 |
Drug Facts
| Class | mTOR inhibitor (mTORC1 — rapamycin analog, first-generation) |
|---|---|
| Mechanism | Sirolimus (rapamycin) binds FKBP-12 and the sirolimus-FKBP12 complex inhibits mTORC1, blocking downstream S6K1 and 4E-BP1 signaling → reduced cell proliferation, protein synthesis, and autophagy suppression. In LAM, TSC1/TSC2 loss leads to mTORC1 hyperactivation → excessive LAM cell proliferation. MILES trial: sirolimus stabilized FEV1, improved functional performance, and reduced VEGF-D. FDA-approved for LAM 2015. |
| Typical dosing | LAM (MILES trial dosing): target trough level 5–15 ng/mL; start 2 mg PO once daily and titrate. Monitor trough levels at 1–2 weeks after each dose change. VEGF-D ≥800 pg/mL at baseline predicts response. |
| Ukraine registered | True |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-05-04 |
Warnings
- Immunosuppression — increased infection risk; do not use with cyclosporine without dose reduction
- Non-infectious pneumonitis — monitor for pulmonary symptoms
Notes
MILES trial (McCormack 2011 NEJM): sirolimus vs placebo in LAM with FEV1 <70% predicted or declining lung function (n=89). Primary endpoint: FEV1 rate of change — sirolimus arm stable (±1.0 mL/mo) vs placebo declining (−12 mL/mo, p<0.001). Secondary: improved DLCO, 6MWD, VEGF-D reduction. FDA approved sirolimus for LAM 2015. Note: benefits are stabilizing (not curative) and may not persist after stopping. Serum VEGF-D ≥800 pg/mL identifies patients most likely to respond and can also confirm LAM diagnosis (avoiding biopsy). Everolimus (another mTORC1 inhibitor) is used for TSC-related SEGA and renal AML; sirolimus is preferred for LAM-specific indication based on MILES data.
Used By
Regimens
REG-SIROLIMUS-LAM- Sirolimus monotherapy (progressive LAM)