Lenvima Dosage

2.1 Patient Selection

​For the pMMR/not MSI-H advanced endometrial carcinoma indication, select patients for treatment with LENVIMA in combination with pembrolizumab based on MMR or MSI status in tumor specimens.

​Information on FDA-approved tests for patient selection is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Important Dosage Information

• Reduce the dose for certain patients with renal or hepatic impairment.
  
• Take LENVIMA once daily, with or without food, 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 Recommended Dosage for Differentiated Thyroid Cancer (DTC)

The recommended dosage of LENVIMA is 24 mg orally once daily until disease progression or until unacceptable toxicity.

2.4 Recommended Dosage for Renal Cell Carcinoma (RCC)

First-Line Treatment of Patients with Advanced RCC

The recommended dosage of LENVIMA is 20 mg orally once daily in combination with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or until unacceptable toxicity or up to 2 years. After completing 2 years of combination therapy, LENVIMA may be administered as a single agent until disease progression or until unacceptable toxicity.

Refer to the pembrolizumab prescribing information for other pembrolizumab dosing information.

Previously Treated RCC

The recommended dosage of LENVIMA is 18 mg in combination with 5 mg everolimus orally once daily until disease progression or until unacceptable toxicity.

Refer to the everolimus prescribing information for recommended everolimus dosing information.

2.5 Recommended Dosage for Hepatocellular Carcinoma (HCC)

The recommended dosage of LENVIMA is based on actual body weight:

• 12 mg for patients greater than or equal to 60 kg or
  
• 8 mg for patients less than 60 kg.

Take LENVIMA orally once daily until disease progression or until unacceptable toxicity.

2.6 Recommended Dosage for Endometrial Carcinoma (EC)

The recommended dosage of LENVIMA is 20 mg orally once daily, in combination with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression.

Refer to the pembrolizumab prescribing information for other pembrolizumab dosing information.

2.7 Dosage Modifications for Adverse Reactions

Recommendations for LENVIMA dose interruption, reduction and discontinuation for adverse reactions are listed in Table 1. Table 2 lists the recommended dosage reductions of LENVIMA for adverse reactions.

Recommended Dose Modifications for Adverse Reactions for LENVIMA in Combination with Pembrolizumab

When administering LENVIMA in combination with pembrolizumab, modify the dosage of one or both drugs as appropriate. Withhold, dose reduce, or discontinue LENVIMA as shown in Table 1. Refer to pembrolizumab prescribing information for additional dose modification information.

Recommended Dose Modifications for Adverse Reactions for LENVIMA in Combination with Everolimus

When administering LENVIMA in combination with everolimus, withhold or reduce the LENVIMA dose first and then the everolimus dose for adverse reactions of both LENVIMA and everolimus. Refer to the everolimus prescribing information for additional dose modification information.

2.8 Dosage Modifications for Severe Renal Impairment

The recommended dosage of LENVIMA for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment (creatinine clearance less than 30 mL/min calculated by Cockcroft-Gault equation using actual body weight) is:

• Differentiated thyroid cancer: 14 mg orally once daily
  
• Renal cell carcinoma: 10 mg orally once daily
  
• Endometrial carcinoma: 10 mg orally once daily

2.9 Dosage Modifications for Severe Hepatic Impairment

The recommended dosage of LENVIMA for patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment (Child-Pugh C) is:

• Differentiated thyroid cancer: 14 mg taken orally once daily
  
• Renal cell carcinoma: 10 mg taken orally once daily
  
• Endometrial carcinoma: 10 mg orally once daily

2.10 Capsule Administration and Preparation of Suspension for Administration

Administration

Oral: Capsule or Suspension

Capsule

• Swallow LENVIMA capsules whole at the same time each day with or without food. Do not crush or chew the LENVIMA capsules.

Suspension

• Prepare oral suspension with water or apple juice and administer at the same time each day with or without food.

Feeding Tube Administration

Suspension

• Prepare suspension for feeding tube administration with water and administer at the same time each day with or without food.

Preparation of Suspension

• Place the required number of capsules, up to a maximum of 5, in a small container (approximately 20 mL capacity) or syringe (20 mL). Do not break or crush capsules.
  
• Add 3 mL of liquid to the container or syringe. Wait 10 minutes for the capsule shell (outer surface) to disintegrate, then stir or shake the mixture for 3 minutes until capsules are fully disintegrated and administer the entire contents.
  
• Next, add an additional 2 mL of liquid to the container or syringe using a second syringe or dropper, swirl or shake and administer. Repeat this step at least once and until there is no visible residue to ensure all of the medication is taken.
  
• If 6 capsules are required for a dose, follow these instructions using 3 capsules at a time.

If LENVIMA suspension is not used at the time of preparation, LENVIMA suspension may be stored in a refrigerator at 36ºF to 46ºF (2ºC to 8ºC) for a maximum of 24 hours in a covered container. If not administered within 24 hours, the suspension should be discarded.

Note: Compatibility has been confirmed for polypropylene syringes and for feeding tubes of at least 5 French diameter (polyvinyl chloride or polyurethane tube) and at least 6 French diameter (silicone tube).