Usual Adult Dose for Soft Tissue Sarcoma

800 mg orally 2 times a day until disease progression or unacceptable toxicity

Use: For the treatment of adult patients with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection

Usual Pediatric Dose for Soft Tissue Sarcoma

16 years and older:
800 mg orally 2 times a day until disease progression or unacceptable toxicity

Use: For the treatment of pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection

Renal Dose Adjustments

Mild, moderate, severe, or end stage renal impairment: No adjustment recommended.

Liver Dose Adjustments

Mild (total bilirubin greater than 1 to 1.5 times upper limit of normal [ULN] or AST greater than ULN) hepatic impairment: No adjustment recommended.
Moderate (total bilirubin greater than 1.5 to 3 x ULN) or severe (total bilirubin greater than 3 times ULN) hepatic impairment: Data not available

Dose Adjustments

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

• First dose reduction: 600 mg orally 2 times a day
• Second dose reduction: 400 mg orally 2 times a day
• Permanently discontinue this drug in patients unable to tolerate 400 mg orally 2 times a day.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
NEUTROPENIA:
Neutrophil count less than 1 x 10(9)/L: Withhold therapy until neutrophil count is greater than or equal to 1 x 10(9)/L or baseline:

• First occurrence: Resume at same dose.
• Second or third occurrence: Resume at reduced dose.
• Fourth occurrence: Permanently discontinue this drug.

THROMBOCYTOPENIA:
Platelet count less than 50 x 10(9)/L: Withhold therapy until platelet count is greater than or equal to 75 x 10(9)/L or baseline:

• First or second occurrence: Resume therapy at reduced dose.
• Third occurrence: Permanently discontinue this drug.

ANEMIA:
Hemoglobin less than 8 g/dL:

• Withhold therapy until improvement to at least Grade 1 or baseline then resume at same or reduced dose.

OTHER ADVERSE REACTIONS:
Grade 3:

• Withhold therapy until improvement to at least Grade 1 or baseline.
• First or second occurrence: Resume at reduced dose.
• Third occurrence: Permanently discontinue this drug.

Grade 4:

• Withhold until improvement to at least Grade 1 or baseline.
• First occurrence: Resume at reduced dose.

Second occurrence: Permanently discontinue this drug.

DOSAGE MODIFICATIONS FOR DRUG INTERACTIONS:
Strong and Moderate CYP450 3A Inhibitors: Avoid coadministration of this drug with moderate or strong CYP450 3A inhibitors. If coadministration with a moderate CYP450 3A inhibitor cannot be avoided, reduce the dose of this drug.

• After discontinuation of the moderate CYP450 3A inhibitor for 3 elimination half-lives, resume this drug at the same dose that was taken prior to initiating the inhibitor.

RECOMMENDED DOSE REDUCTIONS OF THIS DRUG FOR MODERATE CYP450 3A INHIBITORS:

• If the current dose is 800 mg orally 2 times a day reduce to 400 mg orally 2 times a day.
• If the current dose is 600 mg orally 2 times a day reduce to 400 mg orally for the first dose and 200 mg orally for the second dose.
• If the current dose is 400 mg orally 2 times a day reduce to 200 mg orally 2 times a day.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 16 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Swallow tablets whole; do not crush, chew, or dissolve.
• Do not take an additional dose if a dose is missed or vomiting occurs after taking this drug but continue with the next scheduled dose.

Storage requirements:

• Do not store above 30C (86F).

Patient advice:

• Read the patient medication guide each time you refill this medication.
• This drug can cause an increased risk of secondary malignancies (e.g., AML, MDS, T-LBL. Inform your healthcare provider if you experience fatigue, easy bruising, fever, bone pain, or paleness.
• Do not become pregnant while taking this drug.