Sirolimus Albumin-bound (Fyarro) is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors (PEComas).

How to Use Sirolimus Albumin-bound (Fyarro)

Recommended Dosage Regimen

The standard recommended dosage is 100 mg/m², administered via intravenous infusion, with each infusion lasting for 30 minutes.

The administration frequency follows a 21-day treatment cycle, with one dose given on Day 1 and another on Day 8 of each cycle.

This treatment regimen should be continued until disease progression occurs or unacceptable toxicities develop.

Drug Reconstitution and Administration

Sirolimus Albumin-bound (Fyarro) is supplied as a lyophilized powder. Before use, it must be reconstituted with 20 mL of 0.9% Sodium Chloride Injection.

Special attention should be paid to the reconstitution process: The injection should be slowly injected along the inner wall of the vial to avoid direct impact on the lyophilized powder. After injection, allow the vial to stand for at least 5 minutes to fully wet the powder, then gently swirl or invert the vial for at least 2 minutes until the powder is completely dissolved.

The reconstituted suspension should be a milky white, homogeneous liquid with no visible particles. If precipitates or particles are observed, the preparation must be discarded.

Dosage Adjustment of Sirolimus Albumin-bound (Fyarro)

Dosage Adjustment Related to Adverse Reactions

For stomatitis (incidence rate up to 79%):

In case of Grade 2–3 stomatitis, suspend administration until symptoms resolve to Grade ≤1. Maintain the original dosage after the first recurrence; reduce the dosage if recurrence occurs again.

For Grade 4 stomatitis, permanently discontinue the drug.

For myelosuppression (incidence rate: 68% for anemia, 35% each for thrombocytopenia and neutropenia), dosage adjustment is required based on blood test results:

Suspend administration if hemoglobin (Hb) < 8 g/dL; resume treatment with the original dosage after recovery.

Suspend administration if platelets < 100 × 10⁹/L; resume treatment with a reduced dosage after recovery.

For infections (incidence rate 59%):

For Grade 3 infections, suspend administration until symptoms resolve, then resume with a reduced dosage.

For Grade 4 infections, suspend administration and consider permanent discontinuation.

For hypokalemia (incidence rate 44%):

For Grade 2 hypokalemia, suspend administration until symptoms resolve to Grade ≤1, then resume with the original dosage.

For Grade ≥3 hypokalemia, reduce the dosage.

For hyperglycemia (incidence rate 12%): For Grade ≥3 hyperglycemia, suspend administration until symptoms resolve to Grade ≤2, then resume with a reduced dosage.

Dosage Adjustment Related to Drug Interactions

Special caution is required when Fyarro is used concomitantly with CYP3A4 and/or P-gp inhibitors or inducers.

Concomitant use of potent CYP3A4 and/or P-gp inhibitors or inducers should be avoided.

When used concomitantly with moderate or weak CYP3A4 inhibitors, the dosage of Fyarro should be reduced to 56 mg/m².

Precautions for Sirolimus Albumin-bound (Fyarro) Use in Special Populations

Patients with Hepatic Impairment

For patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN, or total bilirubin > 1–1.5 × ULN), the dosage should be reduced to 75 mg/m².

For patients with moderate hepatic impairment (total bilirubin > 1.5–3.0 × ULN), the dosage should be reduced to 56 mg/m².

Use of Fyarro should be avoided in patients with severe hepatic impairment.

Pregnant Women

Based on animal studies and its mechanism of action, Fyarro may cause fetal harm.

In animal experiments, oral sirolimus exhibited embryo/fetal toxicity even at subtherapeutic doses.

Pregnant women should be informed of the potential risks to the fetus. Women of childbearing potential should use effective contraceptive measures during treatment and for 12 weeks after the last dose.

Lactating Women

Currently, there are no data on the distribution of Fyarro in human milk. However, considering the pharmacological effects of sirolimus, it may cause serious adverse reactions in breastfed infants.

It is recommended to avoid breastfeeding during treatment and for 2 weeks after the last dose.