Usual Adult Dose for Renal Cell Carcinoma

400 mg orally 2 times a day
Duration of therapy: Until the patient is no longer benefiting from therapy or until unacceptable toxicity occurs

Comments:

• This drug should be taken on an empty stomach, at least 1 hour before or 2 hours after food.
• The tablets should be swallowed with a glass of water.

• Hepatocellular Carcinoma (HCC): For patients with unresectable HCC
• Renal Cell Carcinoma (RCC): For patients with advanced RCC
• Differentiated Thyroid Carcinoma (DTC): For patients with locally recurrent or metastatic, progressive, DTC that is refractory to radioactive iodine treatment

Usual Adult Dose for Thyroid Cancer

400 mg orally 2 times a day
Duration of therapy: Until the patient is no longer benefiting from therapy or until unacceptable toxicity occurs

Comments:

• This drug should be taken on an empty stomach, at least 1 hour before or 2 hours after food.
• The tablets should be swallowed with a glass of water.

• Hepatocellular Carcinoma (HCC): For patients with unresectable HCC
• Renal Cell Carcinoma (RCC): For patients with advanced RCC
• Differentiated Thyroid Carcinoma (DTC): For patients with locally recurrent or metastatic, progressive, DTC that is refractory to radioactive iodine treatment

Usual Adult Dose for Hepatocellular Carcinoma

400 mg orally 2 times a day
Duration of therapy: Until the patient is no longer benefiting from therapy or until unacceptable toxicity occurs

Comments:

• This drug should be taken on an empty stomach, at least 1 hour before or 2 hours after food.
• The tablets should be swallowed with a glass of water.

• Hepatocellular Carcinoma (HCC): For patients with unresectable HCC
• Renal Cell Carcinoma (RCC): For patients with advanced RCC
• Differentiated Thyroid Carcinoma (DTC): For patients with locally recurrent or metastatic, progressive, DTC that is refractory to radioactive iodine treatment

Renal Dose Adjustments

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

Liver Dose Adjustments

Child-Pugh A or B: No adjustment recommended.
Child-Pugh C: Data not available

Dose Adjustments

Temporary interruption of therapy is recommended in patients undergoing major surgical procedures.

Temporary interruption or permanent discontinuation of therapy may be required for the following:
CARDIOVASCULAR EVENTS:
CARDIAC ISCHEMIA AND/OR INFARCTION:

• Grade 2 and above: Permanently discontinue therapy.

• Grade 3: Interrupt therapy until Grade 1 or less; decrease one dose level (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed; If more than 2 dose reductions are required, therapy will be discontinued.
• Grade 4: Permanently discontinue therapy.

• Grade 2 and above: Permanently discontinue therapy.

• Grade 2 asymptomatic and diastolic pressure 90 to 99 mm Hg: Treat with hypertensive therapy; continue this drug as scheduled and closely monitor blood pressure.
• Grade 2 (symptomatic/persistent) OR Grade 2 symptomatic increase by greater than 20 mm Hg (diastolic) or greater than 140/90 mm Hg if previously within normal limits OR Grade 3: Interrupt therapy until symptoms resolve and diastolic blood pressure is less than 90 mm Hg. Treat with antihypertensives. Reduce dose one dose level (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed; If more than 2 dose reductions are required, therapy will be discontinued.
• Grade 4: Permanently discontinue therapy.

• Monitor electrolytes and electrocardiograms; if QTc is greater than 500 milliseconds or for an increase from baseline of 60 milliseconds or greater: Interrupt therapy and correct electrolyte abnormalities (e.g., magnesium, potassium, calcium); use medical judgement before restarting therapy.

• Greater than Grade 3 ALT in the absence of another causes AST/ALT greater than 3 X ULN with bilirubin greater than 2 X ULN in the absence of another cause: Permanently discontinue therapy.

• Grade 2: Treat on time. Reduce dose one dose level (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed
• Grade 3:
• FIRST OCCURRENCE: Interrupt therapy until Grade 2 or less. Reduce dose one dose level (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed.
• IF NO IMPROVEMENT WITHIN 7 DAYS OR SECOND OR THIRD OCCURRENCE: Interrupt therapy until Grade 2 or less. Reduce dose two dose levels (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed.
• FOURTH OCCURRENCE: Interrupt therapy until Grade 2 or less. Decrease three dose levels (HCC and RCC: 400 mg daily, 200 mg daily, or 400 every other day]; thyroid cancer: 800 mg to 600 mg, 400 mg, and 200 mg) when resumed.
• Grade 4: Permanently discontinue therapy.

• First dose reduction: 400 mg once daily
• Second dose reduction: 400 mg every other day

• Suggested dose modification for the first occurrence: Continue therapy and consider topical treatment for symptomatic relief.
• Suggested dose modification for the second or third occurrence or if there is no improvement within 7 days: Interrupt therapy until toxicity resolves to Grade 0 or 1; when resuming therapy, decrease the dose by one dose level (to 400 mg once daily or 400 mg once every other day).
• Suggested dose modification for the fourth occurrence: Discontinue therapy
• DERMATOLOGIC TOXICITY GRADE 3 (Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, or severe discomfort that interferes with patient ability to work or perform activities of daily living):
• Suggested dose modification for the first occurrence: Interrupt therapy until toxicity resolves to Grade 1 or 0; when resuming therapy, decrease the dose by one dose level (to 400 mg once daily or 400 mg once every other day).
• Suggested dose modification for the second occurrence: Interrupt therapy until toxicity resolves to Grade 0 or 1; ; when resuming therapy, decrease the dose by one dose level (to 400 mg once daily or 400 mg once every other day).
• Suggested dose modification for the third occurrence: Discontinue therapy

• First dose reduction: 600 mg daily dose (400 mg and 200 mg 12 hours apart)
• Second dose reduction: 200 mg twice daily
• Third dose reduction: 200 mg once daily

• DERMATOLOGIC TOXICITY GRADE 2 (Painful erythema and swelling of the hands or feet and/or discomfort affecting normal activities):
• Suggested dose modification for the first occurrence: Decrease dose to 600 mg daily
• Suggested dose modification for no improvement within 7 days at reduced dose OR second: Interrupt therapy until toxicity resolves to Grade 1; if therapy is resumed, decrease the dose
• Suggested dose modification for the third occurrence: Reduce dose to 200 mg once daily
• Suggested dose modification for the fourth occurrence: Permanently discontinue therapy.
• DERMATOLOGIC TOXICITY GRADE 3 (Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, or severe discomfort that interferes with patient ability to work or perform activities of daily living):
• Suggested dose modification for the first occurrence: Interrupt therapy until toxicity resolves to Grade 1; if therapy is resumed, decrease the dose by one dose level (to 600 mg daily dose [400 mg and 200 mg 12 hours apart])
• Suggested dose modification for the second occurrence: Interrupt therapy until toxicity resolves to Grade 1; when therapy is resumed, decrease the dose by 2 dose levels (200 mg twice daily)
• Suggested dose modification for the third occurrence: Discontinue therapy permanently.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• In patients with squamous cell lung cancer

Dialysis

Data not available

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