FYARRO

AbsorptionFollowing administration of FYARRO at the recommended dosage, the estimated mean (%CV) C max and AUC 0-inf of sirolimus in patients with advanced solid tumors were 2590 ng/mL (30% CV) and 22100 ng∙h/mL (50% CV), respectively.

DistributionThe protein binding of sirolimus is >99%, primarily to serum albumin in vitro .

EliminationThe mean elimination half-life of sirolimus is approximately 59 hours (41% CV).

MetabolismSirolimus is metabolized by CYP3A4.

ExcretionFollowing a single ra...

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of FYARRO was assessed in a single-arm study (AMPECT). Thirty-four patients received FYARRO 100 mg/m 2 on Days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity [see Clinical Studies ( 14.1 )] . Among the 34 patients who received FYARRO, 16 (47%) were exposed for 6 mo...

The following adverse reactions have been associated with FYARRO in clinical trials and are discussed in greater detail in other sections of the label [see Warnings and Precautions ( 5 )] . Stomatitis [see Warnings and Precautions ( 5.1 )] Myelosuppression [see Warnings and Precautions ( 5.2 )] Infections [see Warnings and Precautions ( 5.3 )] Hypokalemia [see Warnings and Precautions ( 5.4 )] Hyperglycemia [see Warnings and Precautions ( 5.5 )] Interstitial Lung Disease (ILD) / Non-Infectious P...

FYARRO is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin [see Warnings and Precautions ( 5.8 )] . History of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin. ( 4 )

Stomatitis : Withhold, resume at reduced dose, or permanently discontinue based on severity. ( 5.1 ) Myelosuppression : Monitor blood counts prior to and during FYARRO treatment as clinically indicated. Withhold, resume at reduced dose, or permanently discontinue based on severity. ( 5.2 ) Infections : May result from immunosuppression. Monitor for signs and symptoms of infection. Withhold, resume at reduced dose, or permanently discontinue based on severity. ( 5.3 ) Hypokalemia and hyperglycemi...

7 DRUG INTERACTIONS Strong CYP3A4 and/or P-gp Inhibitors or Inducers : Avoid concomitant use. ( 2.3 , 7.1 ) Moderate or Weak CYP3A4 Inhibitors : Reduce FYARRO dose. ( 2.3 , 7.1 ) 7.1 Effects of Other Drugs on FYARRO CYP3A4 and/or P-gp Inhibitors or Inducers CYP3A4 and/or P-gp inhibitors may increase sirolimus concentrations, which may increase the risk of FYARRO adverse reactions. CYP3A4 and/or P-...