lus everolimus until disease progression or until unacceptable toxicity.
Take LENVIMA and everolimus at the same time each day. If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration.
2.3 Administration Instructions
LENVIMA capsules should be swallowed whole. Alternatively, the capsules can be dissolved in a small glass of liquid. Measure 1 tablespoon of water or apple juice and put the capsules into the liquid without breaking or crushing them. Leave the capsules in the liquid for at least 10 minutes. Stir for at least 3 minutes. Drink the mixture. After drinking, add the same amount (1 tablespoon) of water or apple juice to the glass. Swirl the contents a few times and swallow the additional liquid.
2.4 Dose Modifications for DTC and RCC
Table 1: Adverse Reactions Requiring Dose Modification of LENVIMA in DTC and RCC
Adverse Reaction CTCAE Grade Action Dose Reduce and Resume
LENVIMA
Hypertension Grade 31 Hold Resolves to Grade 0, 1, or 2
Grade 4 Discontinue Do Not Resume
Cardiac Dysfunction Grade 3 Hold Resolves to Grade 0, 1, or baseline
Grade 4 Discontinue Do Not Resume
Arterial Thrombotic Event Any Grade Discontinue Do Not Resume
Hepatotoxicity Grade 3 or 4 Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0-1 or baseline
Hepatic Failure Grade 3 or 4 Discontinue Do Not Resume
Proteinuria Greater than or equal to 2 gm/24 hours Hold Resolves to less than 2 gm/24 hours
Nephrotic Syndrome ------- Discontinue Do Not Resume
Nausea, Vomiting, and Diarrhea2 Grade 3 Hold Resolves to Grade 0, 1, or baseline
Vomiting and Diarrhea2 Grade 4 Discontinue Do Not Resume
Renal Failure or Impairment Grade 3 or 4 Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0-1 or baseline
GI Perforation Any Grade Discontinue Do Not Resume
Fistula Grade 3 or 4 Discontinue Do Not Resume
QTc Prolongation Greater than 500 ms Hold Resolves to less than 480 ms or baseline
RPLS Any Grade Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0 to 1
Hemorrhage Grade 3 Hold Resolves to Grade 0 to 1
Grade 4 Discontinue Do Not Resume
1 Grade 3 despite optimal anti-hypertensive therapy
2 Initiate prompt medical management for nausea, vomiting or diarrhea. Permanently discontinue for Grade 4 vomiting and diarrhea despite medical management
Manage other adverse reactions according to the instructions in Table 2 for DTC or Table 3 for RCC.
Recommendations for Dose Modifications in DTC
Table 2: Dose Modifications for LENVIMA for Persistent and Intolerable Grade 2 or Grade 3 Adverse Reactions or Grade 4 Laboratory Abnormalities in DTCa
Adverse Reaction Modification Adjusted Doseb
First occurrence Interrupt until resolved to
Grade 0-1 or baseline 20 mg (two 10 mg capsules) orally once daily
Second occurrencec Interrupt until resolved to
Grade 0-1 or baseline 14 mg (one 10 mg capsule plus one 4 mg capsule) orally once daily
Third occurrencec Interrupt unt |
