Usual Adult Dose for Von Hippel-Lindau Syndrome

Recommended dose: 120 mg orally once daily until disease progression or unacceptable toxicity

Use: For treatment of adult patients with Von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Renal Dose Adjustments

Mild to moderate [eGFR 30 to 89 mL/min/1.73 m(2)] renal dysfunction: No adjustment recommended.
Severe [eGFR less than 30 mL/min/1.73 m(2)] renal dysfunction: Data not available

Liver Dose Adjustments

Mild [total bilirubin less than or equal to the upper limit of normal (ULN) and aspartate aminotransferase (AST) greater than ULN OR total bilirubin greater than 1 to 1.5 x ULN and any AST] hepatic impairment: No adjustment recommended.
Moderate to severe (total bilirubin greater than 1.5 x ULN and any AST) hepatic impairment: Data not available

Dose Adjustments

Recommended dose reductions:

• First dose reduction: 80 mg orally once daily
• Second dose reduction: 40 mg orally once daily
• Third dose reduction: Permanently discontinue therapy.

• Hemoglobin less than 9 g/dL or transfusion indicated: Withhold therapy until hemoglobin is 9 g/dL or greater; resume at a reduced dose or discontinue depending on the severity of anemia.
• Life-threatening or urgent intervention indicated: Withhold therapy until hemoglobin is 9 g/dL or greater; resume at a reduced dose or permanently discontinue.

• Decreased oxygen saturation with exercise: Consider withholding therapy until resolved; resume at the same dose or at a reduced dose depending on the severity of hypoxia.
• Decreased oxygen saturation at rest or urgent intervention indicated: Withhold therapy until resolved; resume at a reduced dose or discontinue depending on the severity of hypoxia.

Precautions

US BOXED WARNINGS:
EMBRYO-FETAL TOXICITY:

• Exposure to this drug during pregnancy can cause embryo-fetal harm.
• Verify pregnancy status prior to the initiation of this drug.
• Advise patients of these risks and the need for effective nonhormonal contraception. This drug can render some hormonal contraceptives ineffective.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken at the same time each day and may be taken with or without food.
• If a dose of this drug is missed, it can be taken as soon as possible on the same day. Resume the regular schedule the next day. Do not take extra tablets to make up for the missed dose.
• If vomiting occurs any time after taking this drug, do not retake the dose. Take the next dose the next day.
• Advise patients to swallow tablets whole. Do not chew, crush, or split prior to swallowing.

• Store this drug at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F).

• Hematologic: Hemoglobin levels (before initiation and throughout treatment)
• Respiratory: Oxygen saturation (before initiation and throughout treatment)

• Read the Patient Information Leaflet for detailed instructions.
• Severe anemia may occur during treatment. Red blood cell levels will be monitored routinely during treatment. Report all signs and symptoms of anemia to your healthcare provider.
• This drug can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Oxygen levels will be monitored routinely during treatment. Report all signs and symptoms of hypoxia to your healthcare provider.
• Pregnant women and females of reproductive potential should understand the risk to a fetus.
• Females of reproductive potential should use effective nonhormonal contraception while taking this drug and for one week after the last dose.
• Male patients with female partners of reproductive potential should use effective contraception during therapy and for one week after the last dose.
• Breastfeeding is not recommended during therapy with this drug and for one week after the last dose.