Sirolimus (Rapamycin)
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| ID | DRUG-SIROLIMUS |
|---|---|
| Tipo | Fármaco |
| Alegais | RapamuneAçúcarСіролімус (Рапаміцин) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-KAPOSI DIS-LAM |
| Fontes | SRC-MILES-MCCORMACK-2011 |
Fatos sobre as drogas
| Classe | inibidor do mTOR (mTORC1 — análogo da rapamicina, primeira geração) |
|---|---|
| Mecanismo | 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. |
| Dose típica | 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. |
| Ucrânia registada | Verdade |
| NSZU reembolsado | Falso |
| Ucrânia verificada pela última vez | 2026-05-04 |
Avisos
- Imunosupressão — risco aumentado de infecção; não utilizar com ciclosporina sem redução da dose
- Non-infectious pneumonitis — monitor for pulmonary symptoms
Notas
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.
Usado por
Indicação
IND-KAPOSI-1L-IATROGENIC-MTOR-CONVERSION- IND-KAPOSI-1L-IATROGENIC-MTOR-CONVERSION
Esquema terapêutico
REG-SIROLIMUS-KAPOSI-CONVERSION- Conversão de sirolímus (sarcoma Kaposi iatrogénico/ associado a transplantes)REG-SIROLIMUS-LAM- Sirolimus em monoterapia (LAM progressivo)