Important Safety Information

Contraindications

History of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

Warnings and Precautions

FYARRO can cause serious adverse reactions. Withhold, resume at reduced dose, or permanently discontinue FYARRO based on severity (See Dosage and Administration of full Prescribing Information).

Stomatitis: Stomatitis, including mouth ulcers and oral mucositis, occurred in 79% of patients, including 18% Grade 3.

Myelosuppression: FYARRO can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Anemia occurred in 68% of patients; 6% were Grade 3. Thrombocytopenia and neutropenia occurred in 35% of patients each. Obtain blood counts at baseline and every 2 months for the first year of treatment and every 3 months thereafter, or more frequently if clinically indicated.

Infections: FYARRO can cause infections. Infections such as urinary tract infections (UTI), upper respiratory tract infections and sinusitis occurred in 59% of patients. Grade 3 infections occurred in 12% of patients, including a single case each of a UTI, pneumonia, skin, and abdominal infections. Monitor for signs and symptoms of infection.

Hypokalemia: FYARRO can cause hypokalemia. Hypokalemia occurred in 44% of patients, including 12% Grade 3 events. Monitor serum potassium prior to starting FYARRO and supplement potassium as medically indicated.

Hyperglycemia: FYARRO can cause hyperglycemia. Hyperglycemia occurred in 12% of patients, all of which were Grade 3 events. Monitor fasting serum glucose prior to starting FYARRO. During treatment, monitor serum glucose every 3 months in non-diabetic patients, or as clinically indicated. Monitor more frequently in diabetic patients.

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis: FYARRO can cause ILD/non-infectious pneumonitis, which occurred in 18% of patients, all Grades 1 or 2. Monitor for new or worsening respiratory symptoms or radiological changes.

Hemorrhage: FYARRO can cause serious and sometimes fatal hemorrhage. Hemorrhage occurred in 24% of patients, including Grade 3 and Grade 5 events in 2.9% of patients each. Monitor for signs and symptoms.

Hypersensitivity Reactions: FYARRO can cause hypersensitivity reactions, including anaphylaxis. Anaphylaxis, angioedema, exfoliative dermatitis and hypersensitivity vasculitis have been observed with use of oral sirolimus. Monitor for hypersensitivity during and following each FYARRO infusion. Monitor for at least 2 hours following completion of the first infusion and as clinically indicated for each subsequent infusion. Reduce the rate, interrupt infusion, or permanently discontinue based on severity.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential hazard to the fetus and to use effective contraception while using FYARRO and for 12 weeks after the last dose.

Male Infertility: Azoospermia or oligospermia may occur.

Immunizations: Avoid live vaccines.

Adverse Reactions

The most common (≥30%) adverse reactions were stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia.

The most common (≥6%) Grade 3 to 4 laboratory abnormalities were decreased lymphocytes, increased glucose, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase.

Drug Interactions

Strong CYP3A4 and/or P-gp Inhibitors or Inducers: Avoid concomitant use.

Moderate or Weak CYP3A4 Inhibitors: Reduce FYARRO dose.

Use in Specific Populations

Hepatic Impairment: Reduce the dose of FYARRO in patients with mild or moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: May impair fertility in females and males.

Please see full Prescribing Information.