DESCRIPTION

REVLIMID, a thalidomide analogue, is an immunomodulatory agent with antiangiogenic and antineoplastic properties. The chemical name is 3-(4-amino-1-oxo 1,3- dihydro-2H-isoindol-2-yl) piperidine-2,6-dione and it has the following chemical structure:

3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione

The empirical formula for lenalidomide is C₁₃H₁₃N₃O₃, and the gram molecular weight is 259.3.

Lenalidomide is an off-white to pale-yellow solid powder. It is soluble in organic solvent/water mixtures, and buffered aqueous solvents. Lenalidomide is more soluble in organic solvents and low pH solutions. Solubility was significantly lower in less acidic buffers, ranging from about 0.4 to 0.5 mg/ml. Lenalidomide has an asymmetric carbon atom and can exist as the optically active forms S(-) and R(+), and is produced as a racemic mixture with a net optical rotation of zero.

REVLIMID is available in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg and 25 mg capsules for oral administration. Each capsule contains lenalidomide as the active ingredient and the following inactive ingredients: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The 5 mg and 25 mg capsule shell contains gelatin, titanium dioxide and black ink. The 2.5 mg and 10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink. The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide and black ink. The 20 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink.

DOSAGE AND ADMINISTRATION

Recommended Dosage For Multiple Myeloma

REVLIMID Combination Therapy

The recommended starting dose of REVLIMID is 25 mg orally once daily on Days 1-21 of repeated 28-day cycles in combination with dexamethasone. Refer to Section 14.1 for specific dexamethasone dosing. For patients greater than 75 years old, the starting dose of dexamethasone may be reduced [see Clinical Studies]. Treatment should be continued until disease progression or unacceptable toxicity.

In patients who are not eligible for auto-HSCT, treatment should continue until disease progression or unacceptable toxicity. For patients who are auto-HSCT-eligible, hematopoietic stem cell mobilization should occur within 4 cycles of a REVLIMID-containing therapy [see WARNINGS AND PRECAUTIONS].

Dose Adjustments for Hematologic Toxicities During MM Treatment

Dose modification guidelines, as summarized in Table 1 below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID.

HOW SUPPLIED

Dosage Forms And Strengths

Capsules

• 2.5 mg, white and blue-green opaque hard capsules imprinted "REV" on one half and "2.5 mg" on the other half in black ink
• 5 mg, white opaque capsules imprinted "REV" on one half and "5 mg" on the other half in black ink
• 10 mg, blue/green and pale yellow opaque capsules imprinted "REV" on one half and "10 mg" on the other half in black ink
• 15 mg, powder blue and white opaque capsules imprinted "REV" on one half and "15 mg" on the other half in black ink
• 20 mg, powder blue and blue-green opaque hard capsules imprinted "REV" on one half and "20 mg" on the other half in black ink
• 25 mg, white opaque capsules imprinted "REV" on one half and "25 mg" on the other half in black ink

Storage And Handling

White and blue-green opaque hard capsules imprinted "REV" on one half and "2.5 mg" on the other half in black ink:

2.5 mg bottles of 28 (NDC 59572-402-28)
2.5 mg bottles of 100 (NDC 59572-402-00)

White opaque capsules imprinted "REV" on one half and "5 mg" on the other half in black ink:

5 mg bottles of 28 (NDC 59572-405-28)
5 mg bottles of 100 (NDC 59572-405-00)

Blue/green and pale yellow opaque capsules imprinted "REV" on one half and "10 mg" on the other half in black ink:

10 mg bottles of 28 (NDC 59572-410-28)
10 mg bottles of 100 (NDC 59572-410-00)

Powder blue and white opaque capsules imprinted "REV" on one half and "15 mg" on the other half in black ink:

15 mg bottles of 21 (NDC 59572-415-21)
15 mg bottles of 100 (NDC 59572-415-00)

Powder blue and blue-green opaque hard capsules imprinted "REV" on one half and "20 mg" on the other half in black ink.

20 mg bottles of 21 (NDC 59572-420-21)
20 mg bottles of 100 (NDC 59572-420-00)

White opaque capsules imprinted "REV" on one half and "25 mg" on the other half in black ink:

25 mg bottles of 21 (NDC 59572-425-21)
25 mg bottles of 100 (NDC 59572-425-00)

Storage

Store at 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [See USP Controlled Room Temperature].

SIDE EFFECTS

The following clinically significant adverse reactions are described in detail in other sections of the prescribing information:

• Embryo-Fetal Toxicity [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Hematologic Toxicity [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Venous and Arterial Thromboembolism [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Increased Mortality in Patients with CLL [see WARNINGS AND PRECAUTIONS]
• Second Primary Malignancies [see WARNINGS AND PRECAUTIONS]
• Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Severe Cutaneous Reactions[see WARNINGS AND PRECAUTIONS]
• Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
• Tumor Flare Reactions [see WARNINGS AND PRECAUTIONS]
• Impaired Stem Cell Mobilization [see WARNINGS AND PRECAUTIONS]
• Thyroid Disorders [see WARNINGS AND PRECAUTIONS]
• Early Mortality in Patients with MCL [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.