Fotivda (Tivozanib)

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

• Recommended Dose: 1.34 mg once daily with or without food for 21 days on treatment followed by 7 days off treatment (28-day cycle) until disease progression or unacceptable toxicity. (
  
  2.1 Recommended Dosing

  The recommended dosage of FOTIVDA is 1.34 mg taken orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle.

  Continue treatment until disease progression or until unacceptable toxicity occurs.

  Take FOTIVDA with or without food. Swallow the FOTIVDA capsule whole with a glass of water. Do not open the capsule.

  If a dose is missed, the next dose should be taken at the next scheduled time. Do

  not

  take two doses at the same time.
  )
  
• Dose interruptions and/or dose reduction may be needed to manage adverse reactions. (
  
  2.2 Dose Modifications for Adverse Reactions

  Initiate medical management for diarrhea, nausea, or vomiting prior to dose interruption or reduction.

  If dose modifications are required for adverse reactions, reduce the dosage of FOTIVDA to 0.89 mg for 21 days on treatment followed by 7 days off treatment for a 28-day cycle.

  Recommendations for dosage modifications are provided in Table 1.

  Table 1. Dosage Modifications for Adverse Reactions

  Adverse Reaction	SeverityGrades are based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).	Dosage Modifications for FOTIVDA
  Hypertension [see Warnings and Precautions (5.1)]	Grade 3	Withhold for Grade 3 that persists despite optimal anti-hypertensive therapy. Resume at reduced dose when hypertension is controlled at less than or equal to Grade 2.
  	Grade 4	Permanently discontinue.
  Cardiac Failure [see Warnings and Precautions (5.2)]	Grade 3	Withhold until improves to Grade 0 to 1 or baseline. Resume at a reduced dose or discontinue depending on the severity and persistence of adverse reaction.
  	Grade 4	Permanently discontinue.
  Arterial Thromboembolic Events [see Warnings and Precautions (5.3)]	Any Grade	Permanently discontinue.
  Hemorrhagic Events [see Warnings and Precautions (5.5)]	Grade 3 or 4	Permanently discontinue.
  Proteinuria [see Warnings and Precautions (5.6)]	2 grams or greater proteinuria in 24 hours	Withhold until less than or equal to 2 grams of proteinuria per 24 hours. Resume at a reduced dose. Permanently discontinue for nephrotic syndrome.
  Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10)]	Any Grade	Permanently discontinue.
  Other Adverse Reactions	Persistent or intolerable Grade 2 or 3 adverse reaction Grade 4 laboratory abnormality	Withhold until improves to Grade 0 to 1 or baseline. Resume at reduced dose.
  	Grade 4 adverse reaction	Permanently discontinue.
  )
  
• For patients with moderate hepatic impairment, reduce the dose to 0.89 mg for 21 days on treatment followed by 7 days off treatment (28-day cycle). (
  
  2.3 Dosage Modifications for Moderate Hepatic Impairment

  Reduce the recommended dosage of FOTIVDA to 0.89 mg capsule taken orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle for patients with moderate hepatic impairment

  [see USE IN SPECIFIC POPULATIONS (8.7)].
  )
  

Capsules:

• 1.34 mg: bright yellow opaque cap imprinted with "TIVZ" in dark blue ink and a bright yellow opaque body imprinted with "SD" in dark blue ink.
• 0.89 mg: dark blue opaque cap imprinted with "TIVZ" in yellow ink and a bright yellow opaque body imprinted with "LD" in dark blue ink.

• Lactation: Advise not to breastfeed. (
  
  
  8.2 Lactation

  Risk Summary

  There are no data on the presence of tivozanib in human milk, or the effects of tivozanib on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with FOTIVDA and for one month after the last dose.
  )
  
• Females and Males of Reproductive Potential: Can impair fertility. (
  
  
  8.3 Females and Males of Reproductive Potential

  FOTIVDA can cause fetal harm when administered to a pregnant woman

  [see USE IN SPECIFIC POPULATIONS (8.1)]

  .

  Pregnancy Testing

  Verify pregnancy status of females of reproductive potential prior to starting treatment with FOTIVDA.

  Contraception

  Females

  Advise females of reproductive potential to use effective contraception during treatment with FOTIVDA and for one month after the last dose

  [see USE IN SPECIFIC POPULATIONS (8.1)]

  .

  Males

  Advise males with female partners of reproductive potential to use effective contraception during treatment with FOTIVDA and for one month after the last dose

  [see NONCLINICAL TOXICOLOGY (13.1)]

  .

  Infertility

  Females and Males

  Based on findings in animal studies, FOTIVDA can impair fertility in females and males of reproductive potential

  [see NONCLINICAL TOXICOLOGY (13.1)]

  .
  )
  
• Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. (
  
  
  2.3 Dosage Modifications for Moderate Hepatic Impairment

  Reduce the recommended dosage of FOTIVDA to 0.89 mg capsule taken orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle for patients with moderate hepatic impairment

  [see USE IN SPECIFIC POPULATIONS (8.7)].
  ,
  
  
  8.7 Hepatic Impairment

  Reduce the dosage when administering FOTIVDA in patients with moderate (total bilirubin greater than 1.5 to 3 times ULN with any AST) hepatic impairment

  [see DOSAGE AND ADMINISTRATION (2.3)]

  . No dosage modification is recommended for patients with mild (total bilirubin less than or equal to ULN with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST) hepatic impairment. The recommended dosage of FOTIVDA in patients with severe (total bilirubin greater than 3 to 10 times ULN with any AST) hepatic impairment has not been established

  [see CLINICAL PHARMACOLOGY (12.3)]

  .
  )