LENALIDOMIDE

Lenalidomide capsules, a thalidomide analogue, is an immunomodulatory agent with antiangiogenic and antineoplastic properties. The chemical name is 3-(4-amino-1-oxo 1,3-dihydro-2 H -isoindol-2-yl) piperidine-2,6-dione and it has the following chemical structure: 3-(4-amino-1-oxo 1,3-dihydro-2 H -isoindol-2-yl) piperidine-2,6-dione The empirical formula for lenalidomide is C 13 H 13 N 3 O 3 , 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. Lenalidomide capsules are 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: croscarmellose sodium, lactose anhydrous, magnesium stearate and microcrystalline cellulose. The 2.5 mg capsule shell contains gelatin, red iron oxide, yellow iron oxide, titanium dioxide, FD&C blue #1, FD&C red #3, FD&C red #40 and black ink. The 5 mg capsule shell contains gelatin, titanium dioxide, black iron oxide, red iron oxide, yellow iron oxide, FD&C blue #1, FD&C yellow #6 and black ink. The 10 mg capsule shell contains gelatin, titanium dioxide, FD&C blue #1, FD&C red #40, FD&C yellow #6, FD&C yellow #5 and black ink. The 15 mg capsule shell contains gelatin, titanium dioxide, FD&C blue #1, FD&C red #40, FD&C yellow #5, black iron oxide, red iron oxide, yellow iron oxide and black ink. The 20 mg capsule shell contains gelatin, titanium dioxide, FD&C blue #1, FD&C red #40, red iron oxide, yellow iron oxide and black ink. The 25 mg capsule shell contains gelatin, titanium dioxide and black ink. The black imprinting ink contains shellac, strong ammonia solution, black iron oxide. structure

Lenalidomide capsules are a thalidomide analogue indicated for the treatment of adult patients with: Multiple myeloma (MM), in combination with dexamethasone ( 1.1 ). Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities ( 1.2 ). Limitations of Use: Lenalidomide capsules are not indicated and are not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials ( 1.6 ). 1.1 Multiple Myeloma Lenalidomide capsules in combination with dexamethasone are indicated for the treatment of adult patients with multiple myeloma (MM). 1.2 Myelodysplastic Syndromes Lenalidomide capsules are indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. 1.6 Limitations of Use Lenalidomide capsules are not indicated and are not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions ( 5.5 )].

MM combination therapy: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles. ( 2.1 ). MDS: 10 mg once daily ( 2.2 ). Renal impairment: Adjust starting dose based on the creatinine clearance value ( 2.6 ). For concomitant therapy doses, see Full Prescribing Information ( 2.1 , 14.1 ). 2.1 Recommended Dosage for Multiple Myeloma Lenalidomide Capsules Combination Therapy The recommended starting dose of lenalidomide capsules is 25 mg orally once daily on Days 1 to 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 ( 14.1 )] . 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 orunacceptable toxicity. For patients who are auto-HSCT-eligible, hematopoietic stem cell mobilization shouldoccur within 4 cycles of a lenalidomide-containing therapy [see Warnings and Precautions ( 5.12 )] . 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 lenalidomide capsules. Table 1: Dose Adjustments for Hematologic Toxicities for MM Platelet counts Thrombocytopenia in MM When Platelets Recommended Course Days 1 to 21 of repeated 28-day cycle Fall below 30,000/mcL Interrupt lenalidomide capsules treatment, follow CBC weekly Return to at least 30,000/mcL Resume lenalidomide capsules at next lower dose. Do not dose below 2.5 mg daily For each subsequent drop below 30,000/mcL Interrupt lenalidomide capsules treatment Return to at least 30,000/mcL Resume lenalidomide capsules at next lower dose. Do not dose below 2.5 mg daily Absolute Neutrophil counts (ANC) Neutropenia in MM When Neutrophils Recommended Course Days 1 to 21 of repeated 28-day cycle Fall below 1,000/mcL Interrupt lenalidomide capsules treatment, follow CBC weekly Return to at least 1,000/mcL and neutropenia is the only toxicity Resume lenalidomide capsules at 25 mg daily or initial starting dose Return to at least 1,000/mcL and if other toxicity Resume lenalidomide capsules at next lower dose. Do not dose below 2.5 mg daily For each subsequent drop below 1,000/mcL Interrupt lenalidomide capsules treatment Return to at least 1,000/mcL Resume lenalidomide capsules at next lower dose. Do not dose below 2.5 mg daily 2.2 Recommended Dosage for Myelodysplastic Syndromes The recommended starting dose of lenalidomide capsules is 10 mg daily. Treatment is continued or modified based upon clinical and laboratory findings. Continue treatment until disease progression or unacceptable toxicity. Dose Adjustments for Hematologic Toxicities During MDS Treatment Patients who are dosed initially at 10 mg and who experience thrombocytopenia should have their dosage adjusted as follows: Platelet counts If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS If baseline is at least 100,000/mcL When Platelets Recommended Course Fall below 50,000/mcL Interrupt lenalidomide capsules treatment Return to at least 50,000/mcL Resume lenalidomide capsules at 5 mg daily If baseline is below 100,000/mcL When Platelets Recommended Course Fall to 50% of the baseline value Interrupt lenalidomide capsules treatment If baseline is at least 60,000/mcL and returns to at least 50,000/mcL Resume lenalidomide capsules at 5 mg daily If baseline is below 60,000/mcL and returns to at least 30,000/mcL Resume lenalidomide capsules at 5 mg daily If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS When Platelets Recommended Course Fall below 30,000/mcL or below 50,000/mcL with platelet transfusions Interrupt lenalidomide capsules treatment Return to at least 30,000/mcL (without hemostatic failure) Resume lenalidomide capsules at 5 mg daily Patients who experience thrombocytopenia at 5 mg daily should have their dosage adjusted as follows: If thrombocytopenia develops during treatment at 5 mg daily in MDS When Platelets Recommended Course Fall below 30,000/mcL or below 50,000/mcL with platelet transfusions Interrupt lenalidomide capsules treatment Return to at least 30,000/mcL (without hemostatic failure) Resume lenalidomide capsules at 2.5 mg daily Patients who are dosed initially at 10 mg and experience neutropenia should have their dosage adjusted as follows: Absolute Neutrophil counts (ANC) If neutropenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS If baseline ANC is at least 1,000/mcL When Neutrophils Recommended Course Fall below 750/mcL Interrupt lenalidomide capsules treatment Return to at least 1,000/mcL Resume lenalidomide capsules at 5 mg daily If baseline ANC is below 1,000/mcL When Neutrophils Recommended Course Fall below 500/mcL Interrupt lenalidomide capsules treatment Return to at least 500/mcL Resume lenalidomide capsules at 5 mg daily If neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS When Neutrophils Recommended Course Fall below 500/mcL for at least 7 days or below 500/mcL associated with fever (at least 38.5°C) Interrupt lenalidomide capsules treatment Return to at least 500/mcL Resume lenalidomide capsules at 5 mg daily Patients who experience neutropenia at 5 mg daily should have their dosage adjusted as follows: If neutropenia develops during treatment at 5 mg daily in MDS When Neutrophils Recommended Course Fall below 500/mcL for at least 7 days or below 500/mcL associated with fever (at least 38.5°C) Interrupt lenalidomide capsules treatment Return to at least 500/mcL Resume lenalidomide capsules at 2.5 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 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 for MDS: Base subsequent lenalidomide capsules dose increase or decrease on individual patient treatment tolerance [see Dosage and Administration ( 2.2 )] . 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.

Pregnancy ( Boxed Warning , 4.1 , 5.1 , 8.1 ). Demonstrated severe hypersensitivity to lenalidomide ( 4.2 , 5.9 , 5.15 ). 4.1 Pregnancy Lenalidomide 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 )] .

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 ( 5.1 , 5.2 )] Hematologic Toxicity [see Boxed Warning, Warnings and Precautions ( 5.3 )] Venous and Arterial Thromboembolism [see Boxed Warning, Warnings and Precautions ( 5.4 )] Increased Mortality in Patients with CLL [see Warnings and Precautions ( 5.5 )] Second Primary Malignancies [see Warnings and Precautions ( 5.6 )] Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions ( 5.7 )] Hepatotoxicity [see Warnings and Precautions ( 5.8 )] Severe Cutaneous Reactions [see Warnings and Precautions ( 5.9 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.10 )] Tumor Flare Reactions [see Warnings and Precautions ( 5.11 )] Impaired Stem Cell Mobilization [see Warnings and Precautions ( 5.12 )] Thyroid Disorders [see Warnings and Precautions ( 5.13 )] Hypersensitivity [see Warnings and Precautions ( 5.15 )] MM: Most common adverse reactions (≥20%) include diarrhea, fatigue, anemia, constipation, neutropenia, leukopenia, peripheral edema, insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea, asthenia, pyrexia, upper respiratory tract infection, bronchitis, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, and tremor ( 6.1 ). MDS: Most common adverse reactions (>15%) include thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, pharyngitis, and epistaxis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Newly Diagnosed MM – Lenalidomide Capsules Combination Therapy: Data were evaluated from 1613 patients in a large phase 3 study who received at least one dose of lenalidomide capsules with low dose dexamethasone (Rd) given for 2 different durations of time (i.e., until progressive disease [Arm Rd Continuous; N=532] or for up to eighteen 28-day cycles [72 weeks, Arm Rd18; N=540] or who received melphalan, prednisone and thalidomide (Arm MPT; N=541) for a maximum of twelve 42-day cycles (72 weeks). The median treatment duration in the Rd Continuous arm was 80.2 weeks (range 0.7 to 246.7) or 18.4 months (range 0.16 to 56.7). In general, the most frequently reported adverse reactions were comparable in Arm Rd Continuous and Arm Rd18, and included diarrhea, anemia, constipation, peripheral edema, neutropenia, fatigue, back pain, nausea, asthenia, and insomnia. The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18. In the Rd Continuous arm, the most common adverse reactions leading to dose interruption of lenalidomide capsules were infection events (28.8%); overall, the median time to the first dose interruption of lenalidomide capsules was 7 weeks. The most common adverse reactions leading to dose reduction of lenalidomide capsules in the Rd Continuous arm were hematologic events (10.7%); overall, the median time to the first dose reduction of lenalidomide capsules was 16 weeks. In the Rd Continuous arm, the most common adverse reactions leading to discontinuation of lenalidomide capsules were infection events (3.4%). In both Rd arms, the frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or remained stable throughout treatment, except for cataracts. The frequency of onset of cataracts increased over time with 0.7% during the first 6 months and up to 9.6% by the 2nd year of treatment with Rd Continuous. Table 4 summarizes the adverse reactions reported for the Rd Continuous, Rd18, and MPT treatment arms. Table 4: All Adverse Reactions in ≥5% and Grade 3/4 Adverse Reactions in ≥1% of Patients with MM in the Rd Continuous or Rd18 Arms* Note: A subject with multiple occurrences of an adverse reaction is counted only once under the applicable Body System/Adverse Reaction. a All treatment-emergent adverse events in at least 5% of subjects in the Rd Continuous or Rd18 Arms and at least a 2% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm. b All grade 3 or 4 treatment-emergent adverse events in at least 1% of subjects in the Rd Continuous or Rd18 Arms and at least a 1% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm. c Serious treatment-emergent adverse events in at least 1% of subjects in the Rd Continuous or Rd18 Arms and at least a 1% higher frequency (%) in either the Rd Continuous or Rd18 Arms compared to the MPT Arm. d Preferred terms for the blood and lymphatic system disorders body system were included by medical judgment as known adverse reactions for Rd Continuous/Rd18, and have also been reported as serious. e Footnote “a” not applicable. f Footnote “b” not applicable. @ - adverse reactions in which at least one resulted in a fatal outcome. % - adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases). *Adverse reactions included in combined adverse reaction terms : Abdominal Pain : Abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain Pneumonias : Pneumonia, lobar pneumonia, pneumonia pneumococcal, bronchopneumonia, pneumocystis jiroveci pneumonia, pneumonia legionella, pneumonia staphylococcal, pneumonia klebsiella, atypical pneumonia, pneumonia bacterial, pneumonia escherichia, pneumonia streptococcal, pneumonia viral Sepsis : Sepsis, septic shock, urosepsis, escherichia sepsis, neutropenic sepsis, pneumococcal sepsis, staphylococcal sepsis, bacterial sepsis, meningococcal sepsis, enterococcal sepsis, klebsiella sepsis, pseudomonal sepsis Rash : Rash, rash pruritic, rash erythematous, rash maculo-papular, rash generalized, rash papular, exfoliative rash, rash follicular, rash macular, drug rash with eosinophilia and systemic symptoms, erythema multiforme, rash pustular Deep Vein Thrombosis : Deep vein thrombosis, venous thrombosis limb, venous thrombosis Body System Adverse Reaction All Adverse Reactions a Grade 3/4 Adverse Reactions b Rd Continuous (N = 532) Rd18 (N = 540) MPT (N = 541) Rd Continuous (N = 532) Rd18 (N = 540) MPT (N = 541) General disorders and administration site conditions Fatigue % 173 (33) 177 (33) 154 (28) 39 (7) 46 (9) 31 (6) Asthenia 150 (28) 123 (23) 124 (23) 41 (8) 33 (6) 32 (6) Pyrexia c 114 (21) 102 (19) 76 (14) 13 (2) 7 (1) 7 (1) Non-cardiac chest pain f 29 (5) 31 (6) 18 (3) <1% < 1% < 1% Gastrointestinal disorders Diarrhea 242 (45) 208 (39) 89 (16) 21 (4) 18 (3) 8 (1) Abdominal pain % f 109 (20) 78 (14) 60 (11) 7 (1) 9 (2) < 1% Dyspepsia f 57 (11) 28 (5) 36 (7) <1% < 1% 0 (0) Musculoskeletal and connective tissue disorders Back pain c 170 (32) 145 (27) 116 (21) 37 (7) 34 (6) 28 (5) Muscle spasms f 109 (20) 102 (19) 61 (11) < 1% < 1% < 1% Arthralgia f 101 (19) 71 (13) 66 (12) 9 (2) 8 (1) 8 (1) Bone pain f 87 (16) 77 (14) 62 (11) 16 (3) 15 (3) 14 (3) Pain in extremity f 79 (15) 66 (12) 61 (11) 8 (2) 8 (1) 7 (1) Musculoskeletal pain f 67 (13) 59 (11) 36 (7) < 1% < 1% < 1% Musculoskeletal chest pain f 60 (11) 51 (9) 39 (7) 6 (1) < 1% < 1% Muscular weakness f 43 (8) 35 (6) 29 (5) < 1% 8 (1) < 1% Neck pain f 40 (8) 19 (4) 10 (2) < 1% < 1% < 1% Infections and infestations Bronchitis c 90 (17) 59 (11) 43 (8) 9 (2) 6 (1) < 1% Nasopharyngitis f 80 (15) 54 (10) 33 (6) 0 (0) 0 (0) 0 (0) Urinary tract infection f 76 (14) 63 (12) 41 (8) 8 (2) 8 (1) < 1% Upper respiratory tract infection c% f 69 (13) 53 (10) 31 (6) < 1% 8 (1) < 1% Pneumonia c@ 93 (17) 87 (16) 56 (10) 60 (11) 57 (11) 41 (8) Respiratory tract infection % 35 (7) 25 (5) 21 (4) 7 (1) < 1% < 1% Influenza f 33 (6) 23 (4) 15 (3) < 1% < 1% 0 (0) Gastroenteritis f 32 (6) 17 (3) 13 (2) 0 (0) < 1% < 1% Lower respiratory tract infection 29 (5) 14 (3) 16 (3) 10 (2) < 1% < 1% Rhinitis f 29 (5) 24 (4) 14 (3) 0 (0) 0 (0) 0 (0) Cellulitis c < 5% < 5% < 5% 8 (2) < 1% < 1% Sepsis c@ 33 (6) 26 (5) 18 (3) 26 (5) 20 (4) 13 (2) Nervous system disorders Headache f 75 (14) 52 (10) 56 (10) < 1% < 1% < 1% Dysgeusia f 39 (7) 45 (8) 22 (4) < 1% 0 (0.0) < 1% Blood and lymphatic system disorders d Anemia 233 (44) 193 (36) 229 (42) 97 (18) 85 (16) 102 (19) Neutropenia 186 (35) 178 (33) 328 (61) 148 (28) 143 (26) 243 (45) Thrombocytopenia 104 (20) 100 (19) 135 (25) 44 (8) 43 (8) 60 (11) Febrile neutropenia 7 (1) 17 (3) 15 (3) 6 (1) 16 (3) 14 (3) Pancytopenia < 1% 6 (1) 7 (1) < 1% < 1% < 1% Respiratory, thoracic and mediastinal disorders Cough f 121 (23) 94 (17) 68 (13) < 1% < 1% < 1% Dyspnea c,e 117 (22) 89 (16) 113 (21) 30 (6) 22 (4) 18 (3) Epistaxis f 32 (6) 31 (6) 17 (3) < 1% < 1% 0 (0) Oropharyngeal pain f 30 (6) 22 (4) 14 (3) 0 (0) 0 (0) 0 (0) Dyspnea exertional e 27 (5) 29 (5) < 5% 6 (1) < 1% 0 (0) Metabolism and nutrition disorders Decreased appetite 123 (23) 115 (21) 72 (13) 14 (3) 7 (1) < 1% Hypokalemia % 91 (17) 62 (11) 38 (7) 35 (7) 20 (4) 11 (2) Hyperglycemia 62 (12) 52 (10) 19 (4) 28 (5) 23 (4) 9 (2) Hypocalcemia 57 (11) 56 (10) 31 (6) 23 (4) 19 (4) 8 (1) Dehydration % 25 (5) 29 (5) 17 (3) 8 (2) 13 (2) 9 (2) Gout e < 5% < 5% < 5% 8 (2) 0 (0) 0 (0) Diabetes mellitus % e < 5% < 5% < 5% 8 (2) < 1% < 1% Hypophosphatemia e < 5% < 5% < 5% 7 (1) < 1% < 1% Hyponatremia % e < 5% < 5% < 5% 7 (1) 13 (2) 6 (1) Skin and subcutaneous tissue disorders Rash 139 (26) 151 (28) 105 (19) 39 (7) 38 (7) 33 (6) Pruritus f 47 (9) 49 (9) 24 (4) < 1% < 1% < 1% Psychiatric disorders Insomnia 147 (28) 127 (24) 53 (10) < 1% 6 (1) 0 (0) Depression 58 (11) 46 (9) 30 (6) 10 (2) < 1% < 1% Vascular disorders Deep vein thrombosis c% 55 (10) 39 (7) 22 (4) 30 (6) 20 (4) 15 (3) Hypotension c% 51 (10) 35 (6) 36 (7) 11 (2) 8 (1) 6 (1) Injury, Poisoning, and Procedural Complications Fall f 43 (8) 25 (5) 25 (5) < 1% 6 (1) 6 (1) Contusion f 33 (6) 24 (4) 15 (3) < 1% < 1% 0 (0) Eye disorders Cataract 73 (14) 31 ( 6) < 1% 31 ( 6) 14 ( 3) < 1% Cataract subcapsular e < 5% < 5% < 5% 7 ( 1) 0 ( 0) 0 ( 0) Investigations Weight decreased 72 (14) 78 (14) 48 (9) 11 (2) < 1% < 1% Cardiac disorders Atrial fibrillation c 37 (7) 25 (5) 25 (5) 13 (2) 9 (2) 6 (1) Myocardial infarction (including acute) c ,e < 5% < 5% < 5% 10 (2) < 1% < 1% Renal and Urinary disorders Renal failure (including acute) c@,f 49 (9) 54 (10) 37 (7) 28 (5) 33 (6) 29 (5) Neoplasms benign, malignant and unspecified (Including cysts and polyps) Squamous cell carcinoma c e < 5% < 5% < 5% 8 (2) < 1% 0 (0) Basal cell carcinoma c e,f < 5% < 5% < 5% < 1% < 1% 0 (0) After At Least One Prior Therapy for MM: Data were evaluated from 703 patients in two studies who received at least one dose of lenalidomide/ dexamethasone (353 patients) or placebo/dexamethasone (350 patients). In the lenalidomide/dexamethasone treatment group, 269 patients (76%) had at least one dose interruption with or without a dose reduction of lenalidomide compared to 199 patients (57%) in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the lenalidomide/dexamethasone treatment group had at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group. Most adverse reactions and Grade 3/4 adverse reactions were more frequent in patients who received the combination of lenalidomide/dexamethasone compared to placebo/dexamethasone. Tables 6, 7, and 8 summarize the adverse reactions reported for lenalidomide/dexamethasone and placebo/dexamethasone groups. Table 6: Adverse Reactions Reported in ≥5% of Patients and with a ≥2% Difference in Proportion of Patients with MM between the Lenalidomide/dexamethasone and Placebo/dexamethasone Groups Body System Adverse Reaction Lenalidomide/Dex (N=353) n (%) Placebo/Dex (N=350) n (%) Blood and lymphatic system disorders Neutropenia * 149 (42) 22 (6) Anemia † 111 (31) 83 (24) Thrombocytopenia † 76 (22) 37 (11) Leukopenia 28 (8) 4 (1) Lymphopenia 19 (5) 5 (1) General disorders and administration site conditions Fatigue 155 (44) 146 (42) Pyrexia 97 (27) 82 (23) Peripheral edema 93 (26) 74 (21) Chest pain 29 (8) 20 (6) Lethargy 24 (7) 8 (2) Gastrointestinal disorders Constipation 143 (41) 74 (21) Diarrhea † 136 (39) 96 (27) Nausea † 92 (26) 75 (21) Vomiting † 43 (12) 33 (9) Abdominal pain † 35 (10) 22 (6) Dry mouth 25 (7) 13 (4) Musculoskeletal and connective tissue disorders Muscle cramp 118 (33) 74 (21) Back pain 91 (26) 65 (19) Bone pain 48 (14) 39 (11) Pain in limb 42 (12) 32 (9) Nervous system disorders Dizziness 82 (23) 59 (17) Tremor 75 (21) 26 (7) Dysgeusia 54 (15) 34 (10) Hypoesthesia 36 (10) 25 (7) Neuropathy a 23 (7) 13 (4) Respiratory, thoracic and mediastinal disorders Dyspnea 83 (24) 60 (17) Nasopharyngitis 62 (18) 31 (9) Pharyngitis 48 (14) 33 (9) Bronchitis 40 (11) 30 (9) Infections b and infestations Upper respiratory tract infection 87 (25) 55 (16) Pneumonia † 48 (14) 29 (8) Urinary tract infection 30 (8) 19 (5) Sinusitis 26 (7) 16 (5) Skin and subcutaneous system disorders Rash c 75 (21) 33 (9) Sweating increased 35 (10) 25 (7) Dry skin 33 (9) 14 (4) Pruritus 27 (8) 18 (5) Metabolism and nutrition disorders Anorexia 55 (16) 34 (10) Hypokalemia 48 (14) 21 (6) Hypocalcemia 31 (9) 10 (3) Appetite decreased 24 (7) 14 (4) Dehydration 23 (7) 15 (4) Hypomagnesemia 24 (7) 10 (3) Investigations Weight decreased 69 (20) 52 (15) Eye disorders Blurred vision 61 (17) 40 (11) Vascular disorders Deep vein thrombosis * 33 (9) 15 (4) Hypertension 28 (8) 20 (6) Hypotension 25 (7) 15 (4) Table 7: Grade 3/4 Adverse Reactions Reported in ≥2% Patients and with a ≥1% Difference in Proportion of Patients with MM between the Lenalidomide/dexamethasone and Placebo/dexamethasone groups Body System Adverse Reaction Lenalidomide/Dex (N=353) n (%) Placebo/Dex (N=350) n (%) Blood and lymphatic system disorders Neutropenia * 118 (33) 12 (3) Thrombocytopenia † 43 (12) 22 (6) Anemia † 35 (10) 20 (6) Leukopenia 14 (4) < 1% Lymphopenia 10 (3) 4 (1) Febrile neutropenia * 8 (2) 0 (0) General disorders and administration site conditions Fatigue 23 (7) 17 (5) Vascular disorders Deep vein thrombosis * 29 (8) 12 (3) Infections and infestations Pneumonia † 30 (8) 19 (5) Urinary tract infection 5 (1) < 1% Metabolism and nutrition disorders Hypokalemia 17 (5) 5 (1) Hypocalcemia 13 (4) 6 (2) Hypophosphatemia 9 (3) 0 (0) Respiratory, thoracic and mediastinal disorders Pulmonary embolism † 14 (4) < 1% Respiratory distress † 4 (1) 0 (0) Musculoskeletal and connective tissue disorders Muscle weakness 20 (6) 10 (3) Gastrointestinal disorders Diarrhea † 11 (3) 4 (1) Constipation 7 (2) < 1% Nausea † 6 (2) < 1% Cardiac disorders Atrial fibrillation † 13 (4) 4 (1) Tachycardia 6 (2) < 1% Cardiac failure congestive † 5 (1) < 1% Nervous system disorders Syncope 10 (3) < 1% Dizziness 7 (2) < 1% Eye disorders Cataract 6 (2) < 1% Cataract unilateral 5 (1) 0 (0) Psychiatric disorder Depression 10 (3) 6 (2) Table 8: Serious Adverse Reactions Reported in ≥1% Patients and with a ≥1% Difference in Proportion of Patients with MM between the Lenalidomide/dexamethasone and Placebo/dexamethasone Groups Body System Adverse Reaction Lenalidomide/Dex (N=353) n (%) Placebo/Dex (N=350) n (%) For Tables 6, 7 and 8 above: Blood and lymphatic system disorders Febrile neutropenia adverse reactions in which at least one was considered to be life threatening (if the outcome of the reaction was death, it is included with death cases). 6 (2) 0 (0) Vascular disorders Deep vein thrombosis * 26 (7) 11 (3) Infections and infestations Pneumonia adverse reactions in which at least one resulted in a fatal outcome. 33 (9) 21 (6) Respiratory, thoracic, and mediastinal disorders Pulmonary embolism † 13 (4) < 1% Cardiac disorders Atrial fibrillation † 11 (3) < 1% Cardiac failure congestive † 5 (1) 0 (0) Nervous system disorders Cerebrovascular accident † 7 (2) < 1% Gastrointestinal disorders Diarrhea † 6 (2) < 1% Musculoskeletal and connective tissue disorders Bone pain 4 (1) 0 (0) Median duration of exposure among patients treated with lenalidomide/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse reactions between two treatment groups lenalidomide/dexamethasone vs. placebo/dexamethasone. Venous and Arterial Thromboembolism [see Boxed Warning , Warnings and Precautions ( 5.4 )] VTE and ATE are increased in patients treated with lenalidomide capsules. Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe (8.2%) adverse drug reaction at a higher rate in the lenalidomide/dexamethasone group compared to 3.1% and 3.4% in the placebo/dexamethasone group, respectively in the 2 studies in patients with at least 1 prior therapy with discontinuations due to DVT adverse reactions reported at comparable rates between groups. In the NDMM study, DVT was reported as an adverse reaction (all grades: 10.3%, 7.2%, 4.1%), as a serious adverse reaction (3.6%, 2.0%, 1.7%), and as a Grade 3/4 adverse reaction (5.6%, 3.7%, 2.8%) in the Rd Continuous, Rd18, and MPT Arms, respectively. Discontinuations and dose reductions due to DVT adverse reactions were reported at comparable rates between the Rd Continuous and Rd18 Arms (both <1%). Interruption of lenalidomide capsules treatment due to DVT adverse reactions was reported at comparable rates between the Rd Continuous (2.3%) and Rd18 (1.5%) arms. Pulmonary embolism (PE) was reported as a serious adverse drug reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the lenalidomide/dexamethasone group compared to 0.9% (serious or grade 3/4) in the placebo/dexamethasone group in the 2 studies in patients with, at least 1 prior therapy, with discontinuations due to PE adverse reactions reported at comparable rates between groups. In the NDMM study, the frequency of adverse reactions of PE was similar between the Rd Continuous, Rd18, and MPT Arms for adverse reactions (all grades: 3.9%, 3.3%, and 4.3%, respectively), serious adverse reactions (3.8%, 2.8%, and 3.7%, respectively), and grade 3/4 adverse reactions (3.8%, 3.0%, and 3.7%, respectively). Myocardial infarction was reported as a serious (1.7%) or severe (1.7%) adverse drug reaction at a higher rate in the lenalidomide/dexamethasone group compared to 0.6% and 0.6% respectively in the placebo/dexamethasone group. Discontinuation due to MI (including acute) adverse reactions was 0.8% in lenalidomide/dexamethasone group and none in the placebo/dexamethasone group. In the NDMM study, myocardial infarction (including acute) was reported as an adverse reaction (all grades: 2.4%, 0.6%, and 1.1%), as a serious adverse reaction, (2.3%, 0.6%, and 1.1%), or as a severe adverse reaction (1.9%, 0.6%, and 0.9%) in the Rd Continuous, Rd18, and MPT Arms, respectively. Stroke (CVA) was reported as a serious (2.3%) or severe (2.0%) adverse drug reaction in the lenalidomide/dexamethasone group compared to 0.9% and 0.9% respectively in the placebo/dexamethasone group. Discontinuation due to stroke (CVA) was 1.4% in lenalidomide/dexamethasone group and 0.3% in the placebo/dexamethasone group. In the NDMM study, CVA was reported as an adverse reaction (all grades: 0.8%, 0.6%, and 0.6%), as a serious adverse reaction (0.8%, 0.6%, and 0.6%), or as a severe adverse reaction (0.6%, 0.6%, 0.2%) in the Rd Continuous, Rd18, and MPT arms respectively. Other Adverse Reactions: After At Least One Prior Therapy for MM In these 2 studies, the following adverse drug reactions (ADRs) not described above that occurred at ≥1% rate and of at least twice of the placebo percentage rate were reported: Blood and lymphatic system disorders: pancytopenia, autoimmune hemolytic anemia Cardiac disorders: bradycardia, myocardial infarction, angina pectoris Endocrine disorders: hirsutism Eye disorders: blindness, ocular hypertension Gastrointestinal disorders: gastrointestinal hemorrhage, glossodynia General disorders and administration site conditions: malaise Investigations: liver function tests abnormal, alanine aminotransferase increased Nervous system disorders: cerebral ischemia Psychiatric disorders: mood swings, hallucination, loss of libido Reproductive system and breast disorders: erectile dysfunction Respiratory, thoracic and mediastinal disorders: cough, hoarseness Skin and subcutaneous tissue disorders: exanthem, skin hyperpigmentation Myelodysplastic Syndromes: A total of 148 patients received at least 1 dose of 10 mg lenalidomide capsules in the del 5q MDS clinical study. At least one adverse reaction was reported in all of the 148 patients who were treated with the 10 mg starting dose of lenalidomide capsules. The most frequently reported adverse reactions were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions . Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse reactions. The next most common adverse reactions observed were diarrhea (48.6%; 72/148), pruritus (41.9%; 62/148), rash (35.8%; 53/148) and fatigue (31.1%; 46/148). Table 9 summarizes the adverse reactions that were reported in ≥ 5% of the lenalidomide capsules treated patients in the del 5q MDS clinical study. Table 10 summarizes the most frequently observed Grade 3 and Grade 4 adverse reactions regardless of relationship to treatment with lenalidomide capsules. In the single-arm studies conducted, it is often not possible to distinguish adverse reactions that are drug-related and those that reflect the patient’s underlying disease. Table 9: Summary of Adverse Reactions Reported in ≥5% of the Lenalidomide Capsules Treated Patients in del 5q MDS Clinical Study Body System Adverse Reaction Body System and adverse reactions are coded using the MedDRA dictionary. Body System and adverse reactions are listed in descending order of frequency for the Overall column. A patient with multiple occurrences of an adverse reaction is counted only once under the applicable Body System/Adverse Reaction. 10 mg Overall (N=148) Patients with at least one adverse reaction 148 (100) Blood and Lymphatic System Disorders Thrombocytopenia 91 (61) Neutropenia 87 (59) Anemia 17 (11) Leukopenia 12 (8) Febrile Neutropenia 8 (5) Skin and Subcutaneous Tissue Disorders Pruritus 62 (42) Rash 53 (36) Dry Skin 21 (14) Contusion 12 (8) Night Sweats 12 (8) Sweating Increased 10 (7) Ecchymosis 8 (5) Erythema 8 (5) Gastrointestinal Disorders Diarrhea 72 (49) Constipation 35 (24) Nausea 35 (24) Abdominal Pain 18 (12) Vomiting 15 (10) Abdominal Pain Upper 12 (8) Dry Mouth 10 (7) Loose Stools 9 (6) Respiratory, Thoracic and Mediastinal Disorders Nasopharyngitis 34 (23) Cough 29 (20) Dyspnea 25 (17) Pharyngitis 23 (16) Epistaxis 22 (15) Dyspnea Exertional 10 (7) Rhinitis 10 (7) Bronchitis 9 (6) General Disorders and Administration Site Conditions Fatigue 46 (31) Pyrexia 31 (21) Edema Peripheral 30 (20) Asthenia 22 (15) Edema 15 (10) Pain 10 (7) Rigors 9 (6) Chest Pain 8 (5) Musculoskeletal and Connective Tissue Disorders Arthralgia 32 (22) Back Pain 31 (21) Muscle Cramp 27 (18) Pain in Limb 16 (11) Myalgia 13 (9) Peripheral Swelling 12 (8) Nervous System Disorders Dizziness 29 (20) Headache 29 (20) Hypoesthesia 10 (7) Dysgeusia 9 (6) Peripheral Neuropathy 8 (5) Infections and Infestations Upper Respiratory Tract Infection 22 (15) Pneumonia 17 (11) Urinary Tract Infection 16 (11) Sinusitis 12 (8) Cellulitis 8 (5) Metabolism and Nutrition Disorders Hypokalemia 16 (11) Anorexia 15 (10) Hypomagnesemia 9 (6) Investigations Alanine Aminotransferase Increased 12 (8) Psychiatric Disorders Insomnia 15 (10) Depression 8 (5) Renal and Urinary Disorders Dysuria 10 (7) Vascular Disorders Hypertension 9 (6) Endocrine Disorders Acquired Hypothyroidism 10 (7) Cardiac Disorders Palpitations 8 (5) Table 10: Most Frequently Observed Grade 3 and 4 Adverse Reactions Adverse reactions with frequency ≥1% in the 10 mg Overall group. Grade 3 and 4 are based on National Cancer Institute Common Toxicity Criteria version 2. Regardless of Relationship to Study Drug Treatment in the del 5q MDS Clinical Study Adverse Reactions Adverse reactions are coded using the MedDRA dictionary. A patient with multiple occurrences of an adverse reaction is counted only once in the adverse reaction category. 10 mg (N=148) Patients with at least one Grade 3/4 AE 131 (89) Neutropenia 79 (53) Thrombocytopenia 74 (50) Pneumonia 11 (7) Rash 10 (7) Anemia 9 (6) Leukopenia 8 (5) Fatigue 7 (5) Dyspnea 7 (5) Back Pain 7 (5) Febrile Neutropenia 6 (4) Nausea 6 (4) Diarrhea 5 (3) Pyrexia 5 (3) Sepsis 4 (3) Dizziness 4 (3) Granulocytopenia 3 (2) Chest Pain 3 (2) Pulmonary Embolism 3 (2) Respiratory Distress 3 (2) Pruritus 3 (2) Pancytopenia 3 (2) Muscle Cramp 3 (2) Respiratory Tract Infection 2 (1) Upper Respiratory Tract Infection 2 (1) Asthenia 2 (1) Multi-organ Failure 2 (1) Epistaxis 2 (1) Hypoxia 2 (1) Pleural Effusion 2 (1) Pneumonitis 2 (1) Pulmonary Hypertension 2 (1) Vomiting 2 (1) Sweating Increased 2 (1) Arthralgia 2 (1) Pain in Limb 2 (1) Headache 2 (1) Syncope 2 (1) In other clinical studies of lenalidomide capsules in MDS patients, the following serious adverse reactions (regardless of relationship to study drug treatment) not described in Table 9 or 10 were reported: Blood and lymphatic system disorders: warm type hemolytic anemia, splenic infarction, bone marrow depression, coagulopathy, hemolysis, hemolytic anemia, refractory anemia Cardiac disorders: cardiac failure congestive, atrial fibrillation, angina pectoris, cardiac arrest, cardiac failure, cardio-respiratory arrest, cardiomyopathy, myocardial infarction, myocardial ischemia, atrial fibrillation aggravated, bradycardia, cardiogenic shock, pulmonary edema, supraventricular arrhythmia, tachyarrhythmia, ventricular dysfunction Ear and labyrinth disorders: vertigo Endocrine disorders: Basedow's disease Gastrointestinal disorders: gastrointestinal hemorrhage, colitis ischemic, intestinal perforation, rectal hemorrhage, colonic polyp, diverticulitis, dysphagia, gastritis, gastroenteritis, gastroesophageal reflux disease, obstructive inguinal hernia, irritable bowel syndrome, melena, pancreatitis due to biliary obstruction, pancreatitis, perirectal abscess, small intestinal obstruction, upper gastrointestinal hemorrhage General disorders and administration site conditions: disease progression, fall, gait abnormal, intermittent pyrexia, nodule, rigors, sudden death Hepatobiliary disorders: hyperbilirubinemia, cholecystitis, acute cholecystitis, hepatic failure Immune system disorders: hypersensitivity Infections and infestations: infection bacteremia, central line infection, clostridial infection, ear infection, Enterobacter sepsis, fungal infection, herpes viral infection NOS, influenza, kidney infection, Klebsiella sepsis, lobar pneumonia, localized infection, oral infection, Pseudomonas infection, septic shock, sinusitis acute, sinusitis, Staphylococcal infection, urosepsis Injury, poisoning and procedural complications: femur fracture, transfusion reaction, cervical vertebral fracture, femoral neck fracture, fractured pelvis, hip fracture, overdose, post procedural hemorrhage, rib fracture, road traffic accident, spinal compression fracture Investigations: blood creatinine increased, hemoglobin decreased, liver function tests abnormal, troponin I increased Metabolism and nutrition disorders: dehydration, gout, hypernatremia, hypoglycemia Musculoskeletal and connective tissue disorders: arthritis, arthritis aggravated, gouty arthritis, neck pain, chondrocalcinosis pyrophosphate Neoplasms benign, malignant and unspecified: acute leukemia, acute myeloid leukemia, bronchoalveolar carcinoma, lung cancer metastatic, lymphoma, prostate cancer metastatic Nervous system disorders: cerebrovascular accident, aphasia, cerebellar infarction, cerebral infarction, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage, transient ischemic attack Psychiatric disorders: confusional state Renal and urinary disorders: renal failure, hematuria, renal failure acute, azotemia, calculus ureteric, renal mass Reproductive system and breast disorders: pelvic pain Respiratory, thoracic and mediastinal disorders: bronchitis, chronic obstructive airways disease exacerbated, respiratory failure, dyspnea exacerbated, interstitial lung disease, lung infiltration, wheezing Skin and subcutaneous tissue disorders: acute febrile neutrophilic dermatosis Vascular system disorders: deep vein thrombosis, hypotension, aortic disorder, ischemia, thrombophlebitis superficial, thrombosis 6.2 Postmarketing Experience The following adverse drug reactions have been identified from the worldwide post-marketing experience with lenalidomide capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure [see Warnings and Precautions Section ( 5.8 to 5.11 , and 5.13 )] . Endocrine disorders: Hypothyroidism, hyperthyroidism Hepatobiliary disorders: Hepatic failure (including fatality), toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, mixed cytolytic/cholestatic hepatitis, transient abnormal liver laboratory tests Immune system disorders: Angioedema, anaphylaxis, acute graft-versus-host disease (following allogeneic hematopoietic transplant), solid organ transplant rejection Infections and infestations: Viral reactivation (such as hepatitis B virus and herpes zoster), progressive multifocal leukoencephalopathy (PML) Neoplasms benign, malignant and unspecified (including cysts and polyps): Tumor lysis syndrome, tumor flare reaction Respiratory, thoracic and mediastinal disorders: Pneumonitis Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)

Digoxin: Monitor digoxin plasma levels periodically due to increased C max and AUC with concomitant lenalidomide capsules therapy ( 7.1 ). Concomitant use of erythropoietin stimulating agents or estrogen containing therapies with lenalidomide capsules may increase the risk of thrombosis ( 7.2 ). 7.1 Digoxin When digoxin was co-administered with multiple doses of lenalidomide capsules (10 mg/day) the digoxin C max and AUC inf were increased by 14%. Periodically monitor digoxin plasma levels, in accordance with clinical judgment and based on standard clinical practice in patients receiving this medication, during administration of lenalidomide capsules. 7.2 Concomitant Therapies That May Increase the Risk of Thrombosis Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as estrogen containing therapies, should be used with caution after making a benefit-risk assessment in patients receiving lenalidomide capsules [see Warnings and Precautions ( 5.4 )] . 7.3 Warfarin Co-administration of multiple doses of lenalidomide capsules (10 mg/day) with a single dose of warfarin (25 mg) had no effect on the pharmacokinetics of lenalidomide or R- and S-warfarin. Expected changes in laboratory assessments of PT and INR were observed after warfarin administration, but these changes were not affected by concomitant lenalidomide capsules administration. It is not known whether there is an interaction between dexamethasone and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin.

16.2 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. 16.3 Handling and Disposal Care should be exercised in the handling of lenalidomide capsules. Lenalidomide capsules should not be opened or broken. If powder from lenalidomide capsules contacts the skin, wash the skin immediately and thoroughly with soap and water. If lenalidomide capsules contacts the mucous membranes, flush thoroughly with water. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published. 1 Dispense no more than a 28-day supply.