LENVIMA- lenvatinib capsule
LENVIMA- lenvatinib
Eisai Inc.
1 INDICATIONS AND USAGE
1.1 Differentiated Thyroid Cancer
LENVIMA is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
1.2 Renal Cell Carcinoma
LENVIMA is indicated in combination with everolimus for the treatment of patients with advanced RCC following one prior anti-angiogenic therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose for DTC
The recommended daily dose of LENVIMA is 24 mg (two 10 mg capsules and one 4 mg capsule) orally taken once daily with or without food [ see Clinical Pharmacology (12.3)]. Continue LENVIMA until disease progression or until unacceptable toxicity.
Take LENVIMA 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.
2.2 Recommended Dose for RCC
The recommended daily dose of LENVIMA is 18 mg (one 10 mg capsule and two 4 mg capsules) in combination with 5 mg everolimus orally taken once daily with or without food [see Clinical Pharmacology (12.3)]. Continue LENVIMA plus 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 therapy2 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 Dose b
First occurrence Interrupt until resolved toGrade 0-1 or baseline 20 mg (two 10 mg capsules) orally once daily
Second occurrencec Interrupt until resolved toGrade 0-1 or baseline 14 mg (one 10 mg capsule plus one 4 mg capsule) orally once daily
Third occurrencec Interrupt until resolved toGrade 0-1 or baseline 10 mg (one 10 mg capsule) orally once daily
a Initiate medical management for nausea, vomiting, or diarrhea prior to interruption or dose reduction of LENVIMA
b Reduce dose in succession based on the previous dose level (24 mg, 20 mg, or 14 mg per day)c Refers to the same or a different adverse reaction that requires dose modification
Severe Renal or Hepatic Impairment in DTC
For patients with DTC, the recommended dose of LENVIMA is 14 mg taken orally once daily in patients with severe renal impairment (creatinine clearance [CLcr] less than 30 mL/min calculated by the Cockcroft-Gault equation) or severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions ( 5.4, 5.6), Use in Specific Populations ( 8.6, 8.7)].
Recommendations for Dose Modifications in RCC
Table 3: Dose Modifications for LENVIMA for Persistent and Intolerable Grade 2 or Grade 3 Adverse Reactions or Grade 4 Laboratory Abnormalities in RCCa
Adverse Reaction Modification Adjusted Dose b
First occurrence Interrupt until resolved to Grade 0-1 or baseline 14 mg (one 10 mg capsule plus one 4 mg capsule) orally once daily
Second occurrencec Interrupt until resolved to Grade 0-1 or baseline 10 mg (one 10 mg capsule) orally once daily
Third occurrencec Interrupt until resolved to Grade 0-1 or baseline 8 mg (two 4 mg capsules) orally once daily
a Initiate medical management for nausea, vomiting, or diarrhea prior to interruption or dose reduction of LENVIMA
b Reduce dose in succession based on the previous dose level (18 mg, 14 mg, 10 mg, or 8 mg per day)
c Refers to the same or a different adverse reaction that requires dose modification
Recommend ations for Dose Modification of Everolimus in RCC
Review the Full Prescribing Information for everolimus for recommended dose modifications. For toxicities thought to be related to everolimus alone, discontinue, interrupt, or use alternate day dosing. For toxicities thought to be related to both LENVIMA and everolimus, first reduce LENVIMA and then everolimus.
Severe Renal or Hepatic Impairment in RCC
For patients with RCC, the recommended dose of LENVIMA is 10 mg taken orally once daily in patients with severe renal impairment (CLcr less than 30 mL/min calculated by the Cockcroft-Gault equation) or severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions ( 5.4, 5.6), Use in Specific Populations ( 8.6, 8.7)].
3 DOSAGE FORMS AND STRENGTHS
4 mg hard capsule: A yellowish-red body and yellowish-red cap, marked in black ink with "Є" on the cap and "LENV 4 mg" on the body.
10 mg hard capsule: A yellow body and yellowish-red cap, marked in black ink with "Є" on the cap and "LENV 10 mg" on the body.
