Lenalidomide (Page 2 of 12)

2.3 Recommended Dosage for Mantle Cell Lymphoma

The recommended starting dose of lenalidomide capsules is 25 mg/day orally on Days 1 to 21 of repeated 28-day cycles for relapsed or refractory mantle cell lymphoma. Treatment should be continued until disease progression or unacceptable toxicity.

Treatment is continued, modified or discontinued based upon clinical and laboratory findings.

Dose Adjustments for Hematologic Toxicities During MCL Treatment

Dose modification guidelines as summarized below are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicities considered to be related to lenalidomide capsules.

Platelet counts

Thrombocytopenia during treatment in MCL

When Platelets	Recommended Course
Fall below 50,000/mcL	Interrupt lenalidomide capsules treatment and follow CBC weekly
Return to at least 50,000/mcL	Resume lenalidomide capsules at 5 mg less than the previous dose. Do not dose below 5 mg daily

Absolute Neutrophil counts (ANC)

Neutropenia during treatment in MCL

When Neutrophils	Recommended Course
Fall below 1,000/mcL for at least 7 days OR Falls below 1,000/mcL with an associated temperature at least 38.5°C OR Falls below 500/mcL	Interrupt lenalidomide capsules treatment and follow CBC weekly
Return to at least 1,000/mcL	Resume lenalidomide capsules at 5 mg less than the previous dose. Do not dose below 5 mg daily

2.5 Dosage Modifications for Non-Hematologic Adverse Reactions

For non-hematologic Grade 3/4 toxicities judged to be related to lenalidomide capsules, hold treatment and restart at the physician’s discretion at next lower dose level when toxicity has resolved to Grade 2 or below.

Permanently discontinue lenalidomide capsules for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reactions [see Warnings and Precautions (5.9, 5.15)].

2.6 Recommended Dosage for Patients with Renal Impairment

The recommendations for dosing patients with renal impairment are shown in the following table [see Clinical Pharmacology (12.3)].

Table 3: Dose Adjustments for Patients with Renal Impairment

Renal Function (Cockcroft-Gault)	Dose in Lenalidomide Capsules Combination Therapy for MM and MCL	Dose in Lenalidomide Capsules for MDS
CLcr 30 to 60 mL/min	10 mg once daily	5 mg once daily
CLcr below 30 mL/min (not requiring dialysis)	15 mg every other day	2.5 mg once daily
CLcr below 30 mL/min (requiring dialysis)	5 mg once daily. On dialysis days, administer the dose following dialysis.	2.5 mg once daily. On dialysis days, administer the dose following dialysis.

Lenalidomide Capsules Combination Therapy for MM: For CLcr of 30 to 60 mL/min, consider escalating the dose to 15 mg after 2 cycles if the patient tolerates the 10 mg dose of lenalidomide without dose-limiting toxicity.

Lenalidomide Capsules Therapy for MCL and MDS: Base subsequent lenalidomide capsules dose increase or decrease on individual patient treatment tolerance [see Dosage and Administration (2.1 to 2.3)].

2.7 Administration

Advise patients to take lenalidomide capsules orally at about the same time each day, either with or without food. Advise patients to swallow lenalidomide capsules whole with water and not to open, break, or chew them.

3 DOSAGE FORMS AND STRENGTHS

Capsules:

• 5 mg white capsules printed with “NAT” on cap and “5mg” on body of the capsule in black ink.
• 10 mg white capsules printed with “NAT” on cap and “10mg” on body of the capsule in black ink.
• 15 mg white capsules printed with “NAT” on cap and “15mg” on body of the capsule in black ink.
• 25 mg white capsules printed with “NAT” on cap and “25mg” on body of the capsule in black ink.

4 CONTRAINDICATIONS

4.1 Pregnancy

Lenalidomide capsules can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis. This effect was seen at all doses tested. Due to the results of this developmental monkey study, and lenalidomide’s structural similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in females who are pregnant [see Boxed Warning]. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus [see Warnings and Precautions (5.1, 5.2), Use in Special Populations (8.1, 8.3)].

4.2 Severe Hypersensitivity Reactions

Lenalidomide capsules are contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide [see Warnings and Precautions (5.9, 5.15)].

5 WARNINGS AND PRECAUTIONS

5.1 Embryo-Fetal Toxicity

Lenalidomide is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes life-threatening human birth defects or embryo-fetal death [see Use in Specific Populations (8.1)]. An embryo-fetal development study in monkeys indicates that lenalidomide produced malformations in the offspring of female monkeys who received the drug during pregnancy, similar to birth defects observed in humans following exposure to thalidomide during pregnancy.

​ Lenalidomide capsules are only available through the Lenalidomide REMS program [see Warnings and Precautions (5.2)].

Females of Reproductive Potential

Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning lenalidomide capsules therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.

Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with lenalidomide capsules, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide therapy.

Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10 to 14 days and the second test within 24 hours prior to prescribing lenalidomide therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles or every 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3)].

Males

​ Lenalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide capsules and for up to 4 weeks after discontinuing lenalidomide capsules, even if they have undergone a successful vasectomy. Male patients taking lenalidomide capsules must not donate sperm and for up to 4 weeks after discontinuing lenalidomide capsules [see Use in Specific Populations (8.3)].

Blood Donation

Patients must not donate blood during treatment with lenalidomide capsules and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to lenalidomide.