Usual Adult Dose for Malignant perivascular epithelioid cell neoplasm

Recommended dose: 100 mg/m2 as an IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle.
Duration of therapy: Until disease progression or unacceptable toxicity

Use: Adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa)

Renal Dose Adjustments

• Mild and Moderate: No dose adjustment
• Severe: No data available

Liver Dose Adjustments

• Mild (total bilirubin lessor equal ULN, AST greater than ULN or total bilirubin greater than 1 to 1.5×ULN, any AST): 75 mg/m2
• Moderate (total bilirubin greater than 1.5 to 3.0×ULN, any AST): 56 mg/m2
• Severe: Avoid use

Dose Adjustments

DOSE ADJUSTMENTS FOR ADVERSE REACTIONS:

• First Dose Reduction: 75 mg/m2 (25% reduction from 100 mg/m2)
• Second Dose Reduction: 56 mg/m2 (25% from 75 mg/m2)
• Third Dose Reduction: 45 mg/m2 (20% reduction from 56 mg/m2)
• Permanently discontinue: In patients that cannot tolerate treatment after three dose reductions

SPECIFIC ADVERSE REACTIONS:

STOMATITIS

• Grade 2 or 3:
• Withhold treatment until Grade 1 or less
• Restart at same dose
• If recurrence, restart at reduced dose level
• Grade 4:
• Permanently discontinue

ANEMIA

• Grade 2:
• Withhold until Hb is equal or above 8 g/dL
• Restart at the same dose
• Grade 3 or more:
• Withhold until Hb is equal or above 8 g/dL
• Restart at the same dose
• If recurrence, restart at reduced dose level

THROMBOCYTOPENIA

• Grade 2:
• Withhold until platelet count is greater than 100 x 10(9) /L
• Restart at same dose
• Grade 3 or more:
• Withhold until platelet count is greater than 100 x 10(9) /L
• Restart at reduced dose level

NEUTROPENIA

• Grade 2 or 3:
• Withhold until platelet count is greater than 1.5 x 10(9) /L
• Restart at same dose
• Grade 4:
• Withhold until platelet count is greater than 1.5 x 10(9) /L
• Restart at reduced dose level

INFECTIONS

• Grade 3:
• Withhold until resolved
• Restart at reduced dose level
• If recurrence, permanent discontinue
• Grade 4:
• Withhold until resolved
• Restart at reduced dose level or permanent discontinue

HYPOKALEMIA

• Grade 2:
• Withhold until equal or less than Grade 1
• Restart at same dose level
• If recurrence, start at reduced dose level
• Grade 3 or more:
• Withhold until equal or less than Grade 1
• Restart at reduced dose level
• If recurrence, permanently discontinue

HYPERGLYCEMIA

• Grade 3 or more:
• Withhold until equal or less than Grade 2
• Restart at reduced dose level

INTERSTITIAL LUNG DISEASE / NON-INFECTIOUS PNEUMONITIS

• Grade 2:
• Withhold for up to 3 weeks until equal or less than Grade 1
• Restart at reduced dose level
• If not resolved to Grade 1 or less within 3 weeks, permanently discontinue
• Grade 3 or more:
• Permanently discontinue

HEMORRHAGE

• Grade 2 to 3:
• Withhold until equal or less than Grade 1
• Restart at reduced dose level
• If recurrence, permanently discontinue
• Grade 4:
• Permanently discontinue

OTHER ADVERSE REACTIONS

• Grade 3:
• Withhold until equal or less than Grade 1
• Restart at same dose level
• If recurrence, start at reduced dose level
• Grade 4:
• Permanently discontinue

FOR CONCOMITANT USE WITH CYP450 3A4 AND/OR P-GP INHIBITORS AND INDUCERS

• Reduce the dosage to 56 mg/m2 when used concomitantly with a moderate or weak cytochrome P-450 3A4 (CYP450 3A4) inhibitor.
• Avoid concomitant use with drugs that are strong CYP450 3A4 and/or P-glycoprotein (P-gp) inhibitors and inducers and with grapefruit and grapefruit juice.

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

CONTRAINDICATIONS:

• History of severe hypersensitivity to sirolimus, other rapamycin derivates, or albumin

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available.

Other Comments

Administration advice:

• Administer the reconstituted suspension IV over 30 minutes.
• Advise males and females of reproductive potential of the potential risk of imp; aired fertility.
• Advise patients that vaccinations might be less effective while on treatment with this drug.

Storage requirements:

• Unopened vials are stable until the date indicated on the package when stored between 2C to 8C (36F to 46F) in the original package.
• Freezing or thawing does not adversely affect the product stability.
• Reconstituted suspension in the vial should be used immediately but may be refrigerated at 2C to 8C (36F to 46F) for a maximum of 6 hours in the original carton to protect from light. Discard any unused portion.
• Reconstituted suspension in the Infusion bag should be used immediately but may be refrigerated at 2C to 8C (36F to 46F) and protected from light for a maximum of 9 hours
• The total maximum combined refrigerated storage time of reconstituted suspension in the vial and in the infusion bag is 15 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25C) and lighting conditions for a maximum of 4 hours. Discard any unused portion.
• Inform your health care provider of all the medications you take.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

Monitoring:

• Monitor blood counts prior and during treatment.
• Monitor serum potassium prior and during treatment.
• During treatment, monitor serum glucose every 3 months in non-diabetic patients, or as clinically indicated. Monitor serum glucose more frequently in diabetic patients.
• Signs and symptoms of infection, including opportunistic infections
• New or worsening respiratory symptoms
• For sign or symptoms of bleeding
• Monitor for hypersensitivity reactions at least during 2 hours after the first infusion and as clinically indicated for each subsequent infusion.
• Closely monitor patients with liver dysfunction for signs of hepatotoxicity.

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Report any abnormal bleeding to your health care provider.
• Report any symptoms of infection to your health care provider.
• Report immediately any new or worsening respiratory symptoms.
• Promptly contact your healthcare provider or seek emergency care for signs of hypersensitivity reaction including rash, itching, hives, difficulty breathing or swallowing, flushing, chest pain, or dizziness.
• Females of reproductive potential should use effective contraception during treatment and for 12 weeks after your last dose. The same applies for males with female partners of reproductive potential.
• Do not breastfeed during treatment.